Association of depression with anaerobic muscle strengthening activity, moderate
intensity physical activity, long term lipophilic statin usage, and selected comorbidity:
NHANES (National Health and Nutrition Examination Survey) 1999-2012
DISSERTATION
Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy
in the Graduate School of The Ohio State University
By
Causenge Cangin
Graduate Program in Kinesiology
The Ohio State University
2016
Dissertation Committee, listed in Alphabetical order:
Professor Dr. B. Focht, Advisor
Professor Dr. P. Binkley
Professor Dr. R. Harris
Professor Dr. J. Schwartzbaum
Copyrighted by
C Cangin
2016
Abstract
Objectives: Cross sectional data of National Health and Nutrition Examination Survey
(NHANES 1999-2012) were analyzed to examine inverse associations between depression
and exercise. Retrospective case-control study was used to quantify anaerobic “muscle
strengthening activity” associated with depression severity, while controlling for aerobic
activity. Anti-depressive benefits associated with “moderate intensity activity”, and
interactions with prolonged statin treatment were studied.
Methods:
Depression was assessed using a validated “Patient Health Questionnaire (PHQ9)” survey
with depression scores in (0-27) range. PHQ910 is a dichotomous indicator of depression.
Gender-stratified logistic regression was used to estimate odds ratios (OR) of anaerobic
“muscle
strengthening
activity”
associated
with
depression,
while controlling
aerobic activity. Multinomial logistic regression was used to estimate OR of “muscle
strengthening activity” associated with these severity levels of depression: mild (5–9),
dysthymia (10–14), moderate (15–19), major-depression (20–27), in comparison with
reference (0-4). Models adjusted for aerobic activity energy expenditure, age, BMI, and
medical conditions. Subgroups of adults diagnosed with or without osteoarthritis,
ii
rheumatoid arthritis, cancer (of breast, cervix, uterine, prostate, colon rectum, nonmelanoma, melanoma, skin), cardiovascular disease (congestive heart failure, coronary
heart disease, angina pectoris, myocardial infarction, stroke), or metabolic syndrome, were
examined separately. Similar analyses were conducted for “moderate intensity activity”
and depression. Time series logistic models computed OR of exercise and depression with
increasing duration of lipophilic/hydrophilic statin treatment.
Results:
Among 3935 women and 3419 men participating in NHANES during 19992006, women had a higher prevalence of depression than men (8.8% versus 5.7%) and a
lower prevalence of muscle strengthening activity (26% versus 41%). Muscle
strengthening activity was inversely associated with depression (PHQ9≥10) in women
under 50 (OR=0.58; 95% CI=0.41-0.82), all women (OR=0.59; 0.43-0.80), men under 50
(OR=0.79; 0.54-1.10), and all men (OR=0.66; 0.47-0.93), while adjusting for aerobic
activity.
In adults with arthritis, cancer, metabolic syndrome, or CVD, statistically
significant inverse trends existed between muscle strengthening activity and depression
severity with adjustment for aerobic exercise.
Among 5843 women and 4617 men participating in NHANES during 1999-2012,
“moderate intensity activity” was inversely associated with depression (PHQ910) in
women under 50 (OR=0.62; 0.49-0.78), men under 50 (OR=0.54; 0.38-0.76), all women
(OR=0.58; 0.49-0.68), and all men (OR=0.47; 0.37-0.58). Moderate intensity activity was
inversely associated with depression severity in women (mild, dysthymia, moderate,
iii
major-depression: OR=0.80, 0.63, 0.51, 0.30, respectively) and in men (mild, dysthymia,
merged moderate-major-depression: OR=0.71, 0.44, 0.43, respectively).
Prolonged lipophilic statin treatment increased the OR of depression associated
with exercise among women diagnosed with CVD (OR from 0.6 to 0.91; beyond ≥550
days), and among women without any CVD (from 0.69 to 0.89; beyond ≥800 days).
However, prolonged hydrophilic statin did not impact the OR trend. Men had similar
results.
Conclusions: Anaerobic muscle strengthening activity was inversely and independently
associated with depression among healthy US adults, and among those with CVD, cancer,
metabolic syndrome or arthritis (NHANES 1999-2006). Severity of depression was also
inversely related to a more general measure of exercise, “moderate intensity physical
activity” (NHANES 1999-2012). Long term lipophilic statin treatment diminished the
inverse association of exercise and depression.
iv
Dedication
Many ideas in this research originated from the faculty advisors. This document was
made possible only because of the generosity, insights, and wisdom of my major advisor
Dr. Focht and my faculty advisors Dr. Binkley, Dr. Harris, and Dr. Schwartzbaum, listed
in alphabetical order.
This dissertation is dedicated to the faculty advisors listed in reverse alphabetical order:
Dr. Schwartzbaum; Dr. Harris; Dr. Focht; Dr. Binkley.
v
Acknowledgments
Great appreciation and tremendous thankfulness to my major Advisor:
Dr. B. Focht, Ph.D., Advisor;
Genuine gratitude for the wisdom, kindness and guidance received continually from
committee Faculty advisors:
Dr. J. Schwartzbaum, Ph.D.;
Dr. R. Harris, M.D. Ph.D.;
Dr. P. Binkley, M.D. Ph.D.
Thank you to Dr. P. Taylor.
Thankful acknowledgement to both CDC and NHANES for publicly available data
vi
Vita
Bachelor of Science with Honors .................California Institute of Technology
Master of Science ...........................................University of California Davis
Master of Science in Epidemiology ...............The Ohio State University
Publications
(1)
“H. Comer, P. Taylor, S. Malladi, T. Chow, C. Cangin, "Racial Disparity in
Exposure to High-heat cooking Contaminants (Benzo-a-pyrene, MelQx, PhIP), Bisphenol
A, Paraben, Phathalate and Endocrine Disrupter.” The International Journal of Science in
Society 2013, Volume 4, Issue 2, pp.47-53.
(2)
P. Taylor, C. Cangin,“ADHD Co-morbidity of child and juvenile sex offenders”
Official Journal of the World Federation of ADHD Attention Deficit and Hyperactivity
Disorders 2012, ISSN 18666116, Springer Wien New York, 3(2):116-117
(3)
C. Cangin, S. Malladi, “Sprouting Improves the Affordability and Accessibility of
Fresh Vegetables for Low-income Minorities” The International Journal of Science in
Society 2013, 4(2):37-46.
(4)
C. Cangin, P. Taylor, H. Comer, "Public Health Education Connects Common
vii
and Scientific Discourses of Tattoos: Framing Application of the Prospect Theory", ISSN
18366236, International Journal of Science in Society 2012, 3(3):53-60.
Fields of Study
Major Field: Kinesiology
viii
Table of Contents
Abstract ............................................................................................................................... ii
Dedication ........................................................................................................................... v
Acknowledgments.............................................................................................................. vi
Vita.................................................................................................................................... vii
List of Tables ..................................................................................................................... xi
List of Figures .................................................................................................................. xvi
Chapter 1: Research Questions and Literature Gaps .......................................................... 1
Chapter 2: Methods ........................................................................................................... 18
Chapter 3 Data Analysis ................................................................................................... 39
Chapter 4 Results: muscle strengthening activity and depression, 1999 to 2006 ............. 44
Chapter 5 Results: moderately intense physical activity and depression, 1999 to 2012 .. 63
Chapter 6 CVD, physical activity, depression .................................................................. 78
Chapter 7 Metabolic risk factor, metabolic syndrome, physical activity, depression .... 103
Chapter 8 Arthritis, physical activity and depression ..................................................... 119
Chapter 9 Cancer, physical activity and depression ....................................................... 127
Chapter 10 Discussion .................................................................................................... 143
ix
References ....................................................................................................................... 151
x
List of Tables
Table 1. Data availability in biennial NHANES, 1999-2000 to 2011-2012 .................... 21
Table 2. Mapping binary and frequency data from in person WHO interviews to PHQ9
survey ................................................................................................................................ 24
Table 3. Details of mapping from in person WHO interviews to PHQ9 surveys ............ 26
Table 4. Time-varying field limitations ............................................................................ 28
Table 5. Descriptive statistics of adults < 50 years of age: NHANES 1999-2006 .......... 47
Table 6. Descriptive statistics for all adults  18 years old: NHANES 1999-2006 ....... 48
Table 7. Gender-stratified Odds ratios of depression (PHQ9≥10) associated with muscle
strengthening activity for adults under 50 years of age: NHANES 1999-2006 ............... 50
Table 8. Gender-stratified Odds ratios of depression (PHQ9≥10) associated with muscle
strengthening activity for all adults  18 years of age: NHANES 1999-2006 .................. 50
Table 9. Odds ratios of depression severity (mild, dysthymia, moderate, major) and
muscle strengthening activity, stratified by age and gender: NHANES 1999-2006 ........ 55
Table 10. Odds ratios of depression severity (mild, dysthymia, moderate, major) and
muscle strengthening activity, stratified by gender, and absence of CVD/arthritis:
NHANES 1999-2006 ........................................................................................................ 56
xi
Table 11. Odds ratios of depression (PHQ9 ≥ 10) by exercise types in adults under 50
years of age: NHANES 1999-2006................................................................................... 61
Table 12. Odds ratios of depression (PHQ9 ≥ 10) by exercise types in adults  18 years of
age: NHANES 1999-2006 ................................................................................................ 62
Table 13. Descriptive statistics of moderately intense activity and other selected
characteristics among all adults: NHANES 1999-2012.................................................... 64
Table 14. Descriptive statistics of moderately intense activity and other selected
characteristics among adults under 50: NHANES 1999-2012 ......................................... 67
Table 15. Descriptive statistics of moderately intense activity and other selected
characteristics among adults at least 50 years of age: NHANES 1999-2012 ................... 70
Table 16. Odds ratios of depression (PHQ9  10) associated with moderately intense
activity in age-stratified women and men: NHANES 1999-2012 .................................... 73
Table 17. Odds ratios of depression severity (mild, dysthymia, moderate, major)
associated with moderately intense activity: NHANES 1999-2012 ................................. 74
Table 18. Odds ratios of depression severity associated with moderately intense activity
in adults stratified by cardiovascular disease: NHANES 1999-2012 ............................... 80
Table 19. Characteristics by statin categories in women: NHANES 1999-2012 ............. 86
Table 20. Characteristics by statin categories in men: NHANES 1999-2012 .................. 87
Table 21. Distribution of various statin medication usage among men and women with
valid depression, demographics, and physical activity data: NHANES1999-2012.......... 89
Table 22. Odds ratios of depression (PHQ9  10) associated with use of statins in women
with and without CVD diagnoses: NHANES 1999-2012*............................................... 91
xii
Table 23. Odds ratios of depression (PHQ9  10) associated with use of statins in men
with and without CVD diagnoses: NHANES 1999-2012*............................................... 93
Table 24. Odds ratios of depression associated with muscle strengthening activity in
adults diagnosed with CVD: NHANES 1999 to 2006 .................................................... 102
Table 25. Exercise and depression among adults with and without metabolic syndrome
(as defined by NCEP criteria): NHANES 1999 to 2006 for muscle strengthening activity;
NHANES 1999 to 2012 for moderate intensity activity ................................................. 105
Table 26. Odds ratios of depression* associated with muscle strengthening activity in
subgroups of women with metabolic syndrome or its risk factors: NHANES 1999-2006
......................................................................................................................................... 107
Table 27. Odds ratios of depression* (PHQ10) associated with muscle strengthening
activity in subgroups of men with metabolic syndrome or its risk factors: NHANES
1999-2006 ....................................................................................................................... 108
Table 28. Odds Ratios of depression severity associated with “moderate intensity
activity” in adults with NCEP metabolic syndrome: NHANES 1999-2012................... 110
Table 29. Odds Ratios (OR) of depression severity associated with “moderate intensity
activity” among women with waist circumference  35" and men with waist
circumference  40": NHANES 1999-2012.................................................................... 111
Table 30. Odds Ratios (OR) of depression severity associated with “moderate intensity
activity” among adults with high Triglycerides 150 mg/dL: NHANES 1999-2012..... 112
Table 31. Odds Ratios (OR) of depression severity associated with “moderate intensity
activity” among adults with low HDL: NHANES 1999-2012 ....................................... 114
xiii
Table 32. Odds Ratios of depression severity associated with “moderate intensity
activity” among adults with high blood pressure (130/ 85): NHANES 1999-2012 ..... 115
Table 33. Odds Ratios of depression severity associated with “moderate intensity
activity” among adults with fasting glucose  100 mg/dL: NHANES 1999-2012 ......... 116
Table 34. Odds Ratios of depression severity associated with “moderate intensity
activity” among adults with fasting glucose  125 mg/dL: NHANES 1999-2012 ......... 117
Table 35. Odds Ratios of depression severity associated with “moderate intensity
activity” among adults with Rheumatoid arthritis or Osteoarthritis: NHANES 1999-2012
......................................................................................................................................... 122
Table 36. Odds ratios of depression severity associated with “moderate intensity activity”
among adults with any arthritis: NHANES 1999-2012 .................................................. 124
Table 37. Odds ratios of depression associated with muscle strengthening activity among
adults diagnosed with any arthritis (rheumatoid arthritis or osteoarthritis): NHANES 1999
to 2006. ........................................................................................................................... 126
Table 38. Odds ratios of depression severity associated with “moderate intensity activity”
among adults with cancer or arthritis: NHANES 1999-2012 ......................................... 129
Table 39. Odds ratios of depression severity associated with “moderate intensity activity”
among women with breast, cervical, uterine cancer: NHANES 1999-2012 .................. 134
Table 40. Odds ratios of depression associated with “moderate intensity activity” among
men with prostate cancer: NHANES 1999-2012 ............................................................ 135
Table 41. Odds ratios of depression associated with “moderate intensity activity” among
adults with colon rectal cancer: NHANES 1999-2012 ................................................... 136
xiv
Table 42. Odds ratios of depression associated with “moderate intensity activity” among
adults with non-melanoma: NHANES 1999-2012 ......................................................... 138
Table 43. Odds ratios of depression associated with “moderate intensity activity” among
adults with all skin cancer: NHANES 1999-2012 .......................................................... 140
Table 44. Odds ratios of depression associated with muscle strengthening activity among
adults diagnosed with cancer: NHANES 1999-2006...................................................... 142
xv
List of Figures
Figure 1. Odds ratios of depression severity associated with muscle strengthening activity
in women stratified by age: NHANES 1999-2006 ........................................................... 57
Figure 2. Odds ratios of depression severity associated with muscle strengthening activity
in men stratified by age: NHANES 1999-2006 ................................................................ 57
Figure 3. Odds ratios of depression severity associated with muscle strengthening activity
among women without CVD or arthritis: NHANES 1999-2006 ...................................... 58
Figure 4. Odds ratios of depression severity associated with muscle strengthening activity
among men without CVD or arthritis: NHANES 1999-2006 ........................................... 58
Figure 5. Odds ratios of depression severity associated with moderately intense activity in
women: NHANES 1999-2012 .......................................................................................... 76
Figure 6. Odds ratios of depression severity associated with moderately intense activity in
men: NHANES 1999-2012 ............................................................................................... 77
Figure 7. Adjusted Odds ratios of depression severity (mild, dysthymia, moderate, major
depression) associated with moderately intense activity in women with and without CVD:
NHANES 1999-2012 ........................................................................................................ 82
xvi
Figure 8. Adjusted Odds ratios of depression severity (mild, dysthymia, moderate, major
depression) associated with moderately intense activity in men with and without CVD:
NHANES 1999-2012 ........................................................................................................ 83
Figure 9. Comparing the trends of odds ratios of depression associated with “moderate
intensity activity” over duration of statin treatment, among women in different strata of
CVD using a lipophilic/hydrophilic statin: NHANES 1999-2012* ................................. 97
Figure 10. Lipophilic statin treatment in women with CVD: NHANES 1999-2012........ 98
Figure 11. Lipophilic statin treatment in women free of CVD: NHANES 1999-2012 .... 98
Figure 12. Hydrophilic statin in CVD-adjusted women: NHANES 1999-2012 ............. 99
Figure 13. Lipophilic statin treatment in men free of CVD: NHANES 1999-2012 ....... 100
Figure 14. Any statin treatment in men adjusting for CVD: NHANES 1999-2012 ....... 100
Figure 15. Odds ratios of depression severity associated with moderately intense activity
in adults with Rheumatoid arthritis: NHANES 1999-2012 ............................................ 123
Figure 16. Odds ratios of depression severity associated with moderately intense activity
in adults with Osteoarthritis: NHANES 1999-2012 ....................................................... 123
Figure 17. Odds ratios of depression severity (mild, dysthymia, moderate, major)
associated with moderately intense activity among women with cancer: NHANES 19992012................................................................................................................................. 130
Figure 18. Odds ratios of depression severity (mild, dysthymia, moderate, major)
associated with moderately intense activity in men with cancer: NHANES 1999-2012 132
xvii
Chapter 1: Research Questions and Literature Gaps
We investigated the association between the severity level of depression and
physical activity (muscle strengthening activity or moderately intense physical activity)
in the general US population, and in US adults with arthritis, cancer, cardiovascular
disease (CVD), or metabolic syndromes. Availability of secondary data limited our
analyses of physical activity to muscle strengthening activity (NHANES1999-2006) and
moderately intense physical activity (NHANES1999-2012). Using NHANES1999-2006
data, we quantified the dose response patterns between muscle strengthening activity and
the severity level of depression in the general population as well as in chronically ill
subpopulations. Using NHANES1999-2012 data, separate analyses examined the
relationship between moderately intense physical activity and depression severity in the
general adult population and subgroups of adults diagnosed with chronic medical
conditions. Nonparametric trend tests identified the significance of the dose-response
patterns between muscle strengthening activity and depression severity, and between
moderately intense physical activity and depression severity.
In NHANES survey, the phrases "moderate intensity activity", "moderate
intensity sports", and “moderate intensity” exercise were synonymous; in this document,
the phrase 'moderately intense physical activity' was used interchangeably with the above
phrases to refer to all physical activity (performed for work, commuting, fitness,
1
recreation, etc.) that "caused light sweating or slight to moderate increase in breathing or
heart rate for at least ten minutes continuously." Due to the limited space in the tables,
figures, list of tables and list of figures, the shortened version of the phrase "moderate
intensity activity” was used instead.
We also examined whether long term treatment of lipophilic statins or hydrophilic
statins influenced the temporal trend of the odds ratios of “moderately intense physical
activity” associated with depression. An odds ratio is the ratio of the odds of an outcome
given a particular exposure (in the numerator), compared to the odds of an outcome
occurring without that exposure (in the denominator). A lipophilic substance tends to
dissolve in lipid whereas a hydrophilic substance tends to dissolve in water. At various
time points of lipophilic statin treatment, the odds ratios of depression (associated with
“moderately intense physical activity”) were computed separately for women diagnosed
with CVD, and for women without any CVD. At various time points of hydrophilic statin
treatment, the odds ratios of depression (associated with “moderately intense physical
activity”) were computed for women, while adjusting for cardiovascular diseases, age,
BMI, total cholesterol, HDL, cancer, and arthritis.
2
1.1 Muscle strengthening activity and Depression
The relationship between anaerobic muscle strengthening exercise and depression
had not been systematically investigated using data from a nationally representative sample
of the US adult population. Anaerobic muscle strengthening exercise includes push-ups,
bench-press, sit-ups, rowing, weight-lifting activities1, and “activity of persons who use
equipment that primarily involves upper body movement”2. In contrast, aerobic exercise
has been known to alleviate depression in various populations, including healthy adults3,
healthy children and young adolescents4, patients with pulmonary disease5 and pregnant
women6. Past research investigated the interventions of aerobic activity for clinically
depressed patients7, various convenience samples of volunteers8,
9, 10, 11, 12
, patient
referrals13, 14, psychiatric inpatients15, and psychiatric outpatients16. Using objectively
measured accelerometer17 physical activity data from the National Health and Nutrition
Examination Surveys (“NHANES”) 2003-2006 database, Loprinzi showed that even
moderate levels of aerobic exercise are associated with lower levels of depression18. The
lack of national research on anaerobic muscle strengthening exercise and depression is a
gap in the literature.
In NHANES, “muscle strengthening activity” has not yet been studied with respect
to depression. So far, NHANES researchers have investigated “muscle strengthening
activity” with respect to various health topics such as muscle strength, body weight19, youth
fitness20, youth physical activity21, pre-diabetes22, higher insulin sensitivity23, physical
activity guideline24, premature mortality, all-cause mortality25. None of the NHANES
publications had yet specifically studied muscle strengthening activity and depression.
3
This research question was unique because we adjusted for aerobic activity and
medical conditions (arthritis, cancer, cardiovascular diseases) while investigating the
relationship between muscle strengthening physical activity and depression (NHANES
1999-2000 to 2005-2006 cycles) in adults under the age of 50 initially, and then
subsequently in all adults over the age of 18. In contrast, past NHANES literature focused
primarily on the association between aerobic activity/accelerometer measured activity and
depression. NHANES physical activity data consisted of self-reported aerobic physical
activity, self-reported muscle strengthening activity, and accelerometer data. None of the
NHANES publications thus far have investigated the relationship between depression and
muscle strengthening activity. Due to potential confounding, the adjustment of effects of
anaerobic activity for aerobic activity is crucial in delineating the independent antidepressive role of anaerobic muscle strengthening activity.
The use of self-reported muscle strengthening physical activity data in our study
was suitable and well justified because the “objective” accelerometer measurements lack
the ability to record complex motion and muscle strengthening exercise such as bench
pressing, weight lifting, and strength training. “ActiGraph” accelerometers were designed
to measure uni-axial motion, and to assess primarily aerobic physical activity involving
motion around a single axis such as walking and running. The uni-axial ActiGraph
accelerometers used in NHANES were found to often “under-estimate complex movement
patterns because they cannot capture static or dual dynamic-static motion, such as
swimming, bicycling, and weight lifting. Even the newly developed tri-axial accelerometer
like Tritrac-RT3 cannot ascertain complex movement patterns and significantly under4
estimate the energy expenditure of muscle strengthening exercise and complex activity by
about 50%, resulting in energy gap.” Despite the objective value of accelerometers, they
cannot record many muscle strengthening activities such as rowing, bench pressing and
weight lifting, as well as static activity such as bicycling and other complex motions26.
Furthermore, the analyses of self-reported physical activity data had been previously
published in prior NHANES research27, 28.
Addressing this research question is relevant and important because depression is
prevalent. The World Health organization recognized that depression was the third most
burdensome disease worldwide in 2004; depression ranked the eighth place among lower
income nations but in the first place among middle to high-income nations29. We aim to
quantify the relationship between muscle strengthening physical activity and the severity
level of depression in US adults as well as in adults diagnosed with chronic conditions.
Findings from past systematic reviews and meta-analyses have primarily focused
on aerobic activity as the primary intervention of choice for depression. Prior exercise
intervention for depression focused on aerobic activity. In Craft and Landers’ metaanalysis30 of exercise intervention targeting the patient populations with diagnosed clinical
depression or depression from mental illnesses, aerobic activities were the interventions of
choice in most of their studies; they concluded that “running produced the largest effect in
alleviating clinical depression” in comparison to other types of exercise interventions.
Using a small number of studies, Craft and Landers found that “non-aerobic exercise” (the
primary mode of muscle strengthening activity) resulted in significant clinically
meaningful reductions in depression among “patients with diagnosed clinical depression
5
and depression resulting from mentally illness.” The review by North also found that
physical activity had beneficial effects on depression31. In Lawlor Hopker’s metaregression analysis, 16 out of the 17 randomized controlled trials had utilized aerobic
activity as the intervention for depression, while only one randomized controlled trial
investigated “non-aerobic exercise or progressive resistance training” as an intervention
for a sample of 32 participants32. Most of the samples in Hopker’s article were not
nationally representative, with sample sizes ranging from 18 to 156 adults. Past emphasis
on aerobic activity provided the impetus for investigating the association of anaerobic
muscle strengthening activity with depression, independent of adjusted aerobic activity.
We hypothesized that muscle strengthening activity (MSA) was inversely
associated with the prevalence odds of depression (or severity level of depression), even
after adjusting for total aerobic activity energy expenditure, demographic and relevant
biomarkers. The current study differed from the previous NHANES studies in these
following ways. (1) First, we controlled for aerobic activity and medical conditions while
investigating the relationship between muscle strengthening activity and depression.
Aerobic activity is a potential confounder because it has been well known to improve
depressive symptoms. Additionally, aerobic activity may be correlated with anaerobic
activity in many exercise or fitness programs. Adjusting for aerobic activity was essential
in order to illuminate the independent association between muscle strengthening activity
and depression. Other potential confounders of associations between depression and
muscle strengthening activity include debilitating medical conditions such as,
cardiovascular disease CVD (including congestive heart failure, coronary heart disease,
6
angina pectoris, myocardial infarction, ischemic stroke, and hemorrhagic stroke), arthritis,
or cancer. Therefore, controlling for medical conditions and debilitating disease was also
important in delineating the independent relationship between muscle strengthening
activity and depression. (2) Secondly, in order to increase sample size and sub cell count
stability, we created a new mapping technique that translated data from the personal
interviews (World Health Organization WHO Composite International Diagnostic
Interview Version 2.1) to the self-reported validated depression survey named “Patient
Health Questionnaire (PHQ9)”. The face-to-face clinically-assessed WHO depression
interviews were implemented from 1999-2000 to 2003-2004; whereas the subsequent selfreported validated depression survey was collected during and after 2005-2006. (3) Our
study examined all publicly available years of NHANES data containing muscle
strengthening activity data (from 1999-2000 to 2005-2006). Most previous NHANES
studies analyzed a single biennial NHANES dataset, which could not provide sufficient
numbers of adults in special sub-groups for statistical analyses. By combining the multiple
biennial surveys from 1999 to 2005, the total sample size was increased such that there
were sufficiently large numbers of adults in the sub cells with non-missing data for
statistical analyses of special interest sub-populations.
7
1.2 Moderate intensity physical activity and severity of depression in adults with arthritis,
cancer, cardiovascular disease, or metabolic syndrome
Moderate intensity physical activity has not been investigated with respect to the
severity level of depression (i.e. mild, dysthymia, moderate, and major depression) among
adults with chronic diseases using the NHANES data. Past researchers analyzed the
association between the quartiles of moderate intensity physical activity (least physically
active group to most active) and dichotomized (the presence/absence of) depression in the
general US population33. Among older US adults34, moderate intensity physical activity
was studied with respect to dichotomized depression. The severity level of depression,
including mild depression, dysthymia, moderate depression, and major depression, were
not analyzed with respect to moderate intensity physical activity among the general adult
population and among the various chronically ill subgroups.
Although physical activity has been prescribed in the treatment of cancer,
cardiovascular disease (CVD), metabolic syndrome, and arthritis35, many middle aged
women with chronic diseases were sedentary and susceptible to depression. Dontje found
that "most women did not increase their physical activity after diagnosis of CVD, cancer,
arthritis, and diabetes; furthermore, physical activity was not a routine component of the
management of chronic diseases. Most women remained sedentary and physically inactive
after the diagnoses of chronic disease36." Depression was found to be a “stronger predictor
of applying for work disability than arthritic disease activity or response to therapy37.”
Depression and “its comorbid chronic illness were found to be more serious in US women
8
than men; the prevalence odds ratios of comorbid arthritis, CVD, diabetes mellitus and
metabolic syndromes by depression category were significantly higher in women38.” Booth
et al stated that the “lack of physical activity or exercise is a major cause of 35 chronic
diseases such as coronary heart disease, stroke, congestive heart failure, arthritis
(osteoarthritis, rheumatoid arthritis), cancer (colon cancer, breast cancer, endometrial
cancer), metabolic syndromes, insulin resistance, prediabetes, type 2 diabetes 39.”
Depression was known to be associated with “greater prevalence of metabolic syndromes
in primary care based community sample40.” Among adults over the age of forty-five in
Finland, the prevalence of simultaneous metabolic syndromes and depressive symptoms
were higher with low leisure-time physical activity compared to adults with high leisuretime physical activity41. The odd ratios of the severity level of depression (mild, dysthymia,
moderate, major depression) associated with moderate intensity physical activity has not
been systematically examined among various US subgroups diagnosed with cancer,
metabolic syndrome, cardiovascular disease, or arthritis. Therefore, we investigated the
dose-response trends between moderate intensity physical activity and the severity level of
depression in various strata of men and women with arthritis, cancer, CVD, or metabolic
syndrome, using NHANES data from 1999 to 2012.
9
1.3 Duration of statin treatment, moderately intense physical activity and depression
We hypothesize that long term suppression of local synthesis of brain cholesterol
can influence the anti-depressive benefits associated with exercise, because the brain is
“the most cholesterol rich organ. Normal brain cholesterol concentration is over 10 times
higher than the serum cholesterol concentration. Although the brain contains 25% of total
body cholesterol, the brain weights only around 2% to 3% of human body mass. Over 95%
of brain cholesterol is synthesized locally in situ. Very little exchange of cholesterol takes
place between the plasma and the brain42. Oligodendrocytes responsible for myelination
has the highest capacity of cholesterol synthesis in situ. Astrocytes have middle level
capacity of cholesterol synthesis that is at least 2- to 3-fold higher than the capacity of
cholesterol synthesis in neurons & fibroblasts43. In the brain, neurons and fibroblasts have
the lowest capacity of cholesterol synthesis. Most brain cholesterol are un-esterified and
exist in 2 pools: (1) the myelin sheaths of oligodendroglia. Myelin contained 70% lipid &
30% protein, which are opposite to the composition in most cell membrane. Hence 70% of
brain cholesterol exist in the myelin and about 17.5% total body cholesterol are found in
myelin. (2) Secondary pool of cholesterol are found in plasma membranes of astrocytes
and neurons44.” Prolonged suppression of cholesterol synthesis in the brain can counteract
the anti-depressive benefits associated with “moderate intensity physical activity.”
We investigated whether long term treatment with a lipophilic or hydrophilic statin
was associated with depression among women and men without diagnosed cardiovascular
disease, while controlling for physical activity, age, body mass index, cholesterol and
relevant biomarkers. A lipophilic substance tends to dissolve in lipid whereas a hydrophilic
10
substance tends to dissolve in water. Publications using distinct study designs (including
prospective cohort studies, national cohort studies, case control studies, health service
insurance database linkage studies) have found contrasting (positive, negative, neutral)
relationships between statin and depression. Conflicting findings of this controversial topic
continue to persist in the literature45.
Recent studies found that statin was beneficial and lowered the risk of depression.
Biennial data from the Heart and Soul study in San Francisco suggested that statin
decreased the risk of subsequent depression in patients with coronary heart disease46.
Findings from health insurance database supported that statin usage was associated with a
lower risk of depression in patients with hyperlipidemia47. Multiple years of statin
treatment was associated with reduced risk of depression among 371 outpatients with
coronary artery disease recruited from cardiology clinic48. Using drug filling medication
data from the San Antonio Military Tricare database and subsequent incident of depression,
Mansi found that the risk of depression was similar between statin users and non-users49.
In a recent study of the national Swedish cohort, the use of any type of statin “was
associated with a reduction in risk of depression in individuals over forty years of age50.”
Kim found that “statin use was associated with a reduced risk of depression at one year
after stroke51”; however, it remained unclear whether the improved stroke outcome had
directly alleviated depression (regardless of statins), or whether the inherent
pharmacological mechanisms of statin had directly improved depression (regardless of the
cardiovascular condition of the subjects). Stroke and other cardiovascular diseases were
strong confounders of the research question asking whether statins were associated with
11
depression. Hence, adult participants were stratified by cardiovascular diseases in
subsequent analyses relating to statin usage.
Mechanistically, Tuccori described these following seven “non-mutually exclusive
pathological pathways that can explain the adverse neuropsychiatric events associated with
statin52. (1) Prolonged statin usage can deplete isoprenoid formation, undermine neuroplasticity, impair memory and cognitive functions by causing the loss of Rho GTPase (the
Rho-guanosine triphosphatase protein, which are used for signaling in the formation and
structural remodeling of synapses), and promote neural cell death. (2) Statin inhibits the
production of coenzyme-Q10, inhibits mevalonate enzyme biosynthesis, and increases
oxidative stress. (3) Lipophilic statin can cross the blood-brain barrier and excessively
inhibit brain cholesterol bio-synthesis in-situ. Suppression of brain cholesterol synthesis
can disrupt the synaptic cholesterol homeostasis and reduce the necessary myelin
formation. Most reports of memory loss and cognitive impairment have been linked to
lipophilic statins. (4) Chronic long term brain cholesterol depletion perturbs the membrane
lipid rafts (MLR) and impairs both the serotonin and dopamine neurotransmission.
Cholesterol is a fundamental component of cell membrane and essential element of MLR
which are pivotal for synaptic function. Vevera reported that long-term treatment of
lipophilic simvastatin Zocor had different effects on serotonin transmission than short-term
treatment; significant increase in platelet serotonin activity during simvastatin treatment
indicated the vulnerability to depression among simvastatin users53. High dose of
simvastatin has been shown to up-regulate the dopamine D1 and D2 receptor expression in
prefrontal cortex, and exert psychotropic effect54. In biochemistry, Shrivastava found that
12
chronic depletion of brain cholesterol via statin impairs the function and dynamics of
human serotonin (1A) receptors55. (5) Low brain cholesterol reduces the synthesis of neurosteroids, impairs the modulation of neuronal excitability through interaction with GABA
receptors, and thereby contributes to anxiety, depression, and mood disorders. (6) Low
neuronal cholesterol increases the phosphorylation of tau-protein and cell death. (7) Statins
enhance the release of omega-6 arachidonic acid, which inhibits the protective effects of
omega-3 (EPA and DHA); decreased levels of omega-3 fatty acids are correlated with
worsened depression. These mechanisms can manifest differently depending on factors
such as the duration, the dosage, the lipophilicity of statin treatment, as well as specific
patient characteristics and baseline health conditions. Expert opinion in Pharmacotherapy
article stated that “statins could lead to depression by lowering cholesterol, by disturbing
serotonin system and neurosteroids56.”
National longitudinal studies, population studies, randomized controlled trials, and
clinical case reports have supported the adverse association between statin use and
depression. Using data from the National Heart, Lung, and Blood Institute (NHLBI)
Women's Ischemia Syndrome Evaluation (WISE), Olson found that women on statins had
worse aggressive hostility and depression scores than women not taking statins57. The New
Zealand Centre for Adverse Reactions Monitoring (CARM) reported serious psychiatric
disturbances in association with statin treatment, and that stated that “decreased brain cell
membrane cholesterol is important in the etiology of psychiatric reactions”58. In the Punjab
India population, stain use was associated with significantly higher risk of depression
among type 2 diabetic adults59. In a Taiwan population-based longitudinal study, regular
13
statin usage elevated the incidence rate and the hazard ratio of depression in stroke patients,
when compared to nonusers of statin60. In a population study of Sardinian elder people
living independently in their home, statin usage was associated with depression in latelife61. Randomized double-blind controlled trial by Hyyppä found that lipophilic
“Simvastatin at 20mg/day for 12 weeks resulted in a statistically significant increase of
depression in healthy middle-aged men62.” Case studies of Dutch patients reported that
simvastatin treatment had resulted in depression, anxiety and suicidal ideation63. In a study
of women conducted at the Mayo Clinic, some patients reported the onset of depression
after one month of statin treatment64. Among adults with mood disorders living in the
community, the prevalence of suicidal ideation was significantly higher or more than
double in those adults taking lipophilic statins65.
Neutral associations between statin use and depression have also been reported for
national cohort studies. In a Switzerland prospective cohort study, Glaus found that
"regular statin usage at baseline did not reduce the incidence of major depression during
follow-up, regardless of sex or age" and “their data do not support a large scale preventive
treatment of depression using statin in adults66." In Singapore Longitudinal Ageing Studies
cohort, statin use was associated with fewer depressive symptoms in older women, and
more depressive symptoms in older men67. In Macedo’s meta-analysis article, four studies
were used to conclude that “statin use was not related to any increased risk of depression68,
even though the authors admitted that “marked heterogeneity of effect existed across
studies.”
14
In examining statin use and depression, most past studies did not control for
physical activity, and the long term duration of statin treatment exceeding 1 year. It remains
unclear whether long term duration of lipophilic or hydrophilic statin treatment influences
the inverse association between moderately intense physical activity and depression among
adults diagnosed with CVD and among adults without any CVD. The relationship between
moderately intense physical activity and depression among long term users of lipophilic
statins has not been systematically studied in the general US population. Adjustment of
estimates for potential confounding by the presence of medical conditions such as CVD,
cancer, metabolic syndrome or arthritis is critical in such studies. We hypothesized that
long term lipophilic statin treatment differs from long term hydrophilic statin treatment in
their relationship to the anti-depressive effects of physical activity, after controlling for
age, body mass index, and medical conditions. No NHANES study has thus far studied
depression with respect to the long term duration of lipophilic statin treatment in CVDstratified adults.
Due to the growing number of statin users, understanding whether prolonged
lipophilic statin treatments modifies the anti-depressive effect of exercise is important.
Lipid regulators and anti-depressants were the top two therapeutic classes of medications
by the number of prescriptions, according to National Prescription Audit in December of
2010 and then again in November 201469.
Levin et al. suggested that the impact of statin medications on the brain depends
on the lipophilicity of the medications and their distribution coefficients 70. The “bloodbrain barrier permeability of medications affected their ability to act on the central
15
nervous system. The blood brain permeability of a medication was found to be related to
its octanol/water partition coefficient and its molecular weight.” The distribution
coefficient (log Doctanol/water) was defined as the logarithm of the ratio of the lipid octanol
solute concentration in all forms (ionized and unionized) divided by the water aqueous
solute concentration in all forms (ionized and unionized). This was equivalent to the log
of the sum of concentration of all forms (ionized and unionized) in lipid minus the log of
the sum of concentration of all forms (ionized and unionized) in water. The blood-brain
barrier trans-membrane permeability coefficients71, and the distribution coefficients of
various statins in the following pages came from published derived data of
pharmacological publication72.
log Doctanol/water = Log( [solute]ionized,octanol + [solute]unionized,octanol )
-
Log( [solute]ionized,water + [solute]unionized,water )
16
The blood-brain barrier (BBB) trans-membrane permeability coefficients (Ptrans)
in the unit of μL/min/[cm2] of various statins were published by citations 68, 69, 70.
Lovastatin has the highest (8.32 μL/min/[cm2]) blood-brain barrier trans-membrane
permeability coefficient Ptrans value; its Log D min and Log D max values are 1.55 and
3.91, respectively68, 69, 70. Simvastatin has the second highest blood-brain barrier transmembrane permeability coefficient Ptrans value (4.76 μL/min/[cm2]), with corresponding
Log D min, Log D max values as 1.88 and 4.4, respectively68, 69, 70. Pitavastatin has the
Ptrans value of 1.62, with Log D min value of 1.5, and Log D max value of 1.5 68, 69, 70.
Atorvastatin has the lowest trans-membrane permeability coefficient Ptrans value (1.35
μL/min/[cm2]) among all the lipophilic statin, with Log D min, Log D max values as 1,
1.25, respectively68, 69, 70. Fluvastatin has Ptrans value of 0.09, Log D min value of 1, Log
D max value of 1.2568, 69, 70. Pravastatin has Ptrans value of 0.0755, Log D min value of 1, and Log D max value of -0.47 68, 69, 70. Rosuvastatin has Ptrans value of 0.03775, Log
D min value of -0.5, and Log D max value of -0.25 68, 69, 70. As published by Levin et al,
the lipophilic statins have higher blood-brain barrier trans-membrane permeability than
the hydrophilic statins.
Long term treatment and usage of lipophilic statins with high blood brain barrier
permeability could play a role in modifying the inverse association between physical
activity and depression among adults without diagnosed cardiovascular diseases, as well
as adults with diagnosed cardiovascular diseases. Based on the pharmacological literature,
long term hydrophilic statin treatment would yield different results from long term
lipophilic statin treatment.
17
Chapter 2: Methods
2.1 Study Design and Participants
The study design was cross-sectional and the dataset consisted of aggregated
biennial survey data of de-identified US civilian adult participants. The National Health
and Nutrition Examination Survey (NHANES) datasets used in our analyses were collected
biennially, 1999-2012. Nationally representative data NHANES data reported by adults
aged 18-80 years were used to investigate the relationship between muscle strengthening
exercise, moderately intense physical activity and the severity of depressive symptoms, as
well as to study the role of different types of statin. Sampling methods of NHANES were
designed to produce nationally representative data that accurately reflect the noninstitutionalized US civilian population. This study utilized secondary datasets available in
the public domain. This study was exempted from the review process of the Institutional
Review Board at The Ohio State University Medical Center because the datasets were
publicly available and the adult participants were de-identified. Table 1 illustrates the
NHANES data available on depression, muscle strengthening activity, and physical
activity data from 1999-2000 to 2011-2012. No imputation was performed for missing data
throughout all analyses. Complete case analysis was consistently utilized in all analyses.
18
In order to examine the research question of muscle strengthening activity and
depression while controlling for aerobic activity, we pooled NHANES data from 19992000 to 2005-2006. The final sample contained 7354 adults (consisting of 3935 women
and 3419 men), of which a subset contained 5459 adults under fifty years of age (containing
2445 men and 3014 women). Different sets of biennial data were pooled to address
different research questions due to limitation imposed by data availability from survey
structure modification over the decade. These samples included adults with valid and nonmissing muscle strengthening activity, depression, demographic (age, gender, BMI), and
medical conditions data. Although there were a total number of 41,474 adults during 19992006, most of them had missing physical activity or missing depression data. Only 7890
adults had completed either the face-to-face depression interviews (1999 to 2004) or the
self-reported PHQ9 depression survey (2005-2006). The requirement of non-missing data
in physical activity, demographics and medical conditions further restricted the sample size
to the 7354 adults with muscle strengthening data.
For the research question concerning “moderate intensity activity” and depression,
as well as the role of lipophilic statin, the NHANES data from the 1999-2000 to 2011-2012
biennial cycles were combined in order to maximize the number of adults in the final
sample. Pooling the decade of data was absolutely necessary due to (i) missing data, (ii)
redesigned survey structures, and (iii) the low number of men with valid non-missing more
severe depression data and exercise data. Moderately intense physical activity is the only
physical activity measurement with sufficiently non-missing depression data and nonmissing medication data during 1999-2012. By combining data across the years, the sample
19
sizes were increased so that sub-cell sizes were sufficiently large for statistical analyses.
The final sample contained 10,460 adults (consisting of 5,843 women and 4,617 men) with
valid and non-missing data. Even after pooling data across the decade, the number of men
taking a hydrophilic statin remained low thereby limiting statistical analysis.
Selection bias did not appear to impact the final sample of muscle strengthening
activity analysis. The prevalence of muscle strengthening activity in our final analytic
samples was similar to the prevalence of muscle strengthening activity in the entire sample
of individuals. In the final sample of 5459 adults under 50 years of age with muscle
strengthening data, the prevalence of muscle strengthening was 32%. In the larger sample
of 7890 adults under 50 years of age, the prevalence of muscle strengthening activity was
30%. The proportion of adults performing “muscle strengthening activities” in the final
sample was similar to that of the larger sample of adults under 50 years of age.
Selection bias also did not appear to impact the study of moderately intense physical
activity and statin use. The prevalence of moderately intense physical activity was similar
among the various samples of women at different durations of statin treatment. In women
free of CVD, the percentages of women who exercised at moderate intensity in a typical
month were 57.1%, 56.6%, 57.4% for the durations of lipophilic statin treatment at 100
days, 400 days, and 800 days, respectively. In women with CVD, the percentages of
women who exercised at moderate intensity in a typical month hovered around 37.7% for
the duration of lipophilic statin treatment lasting up to and beyond two years. Among
women taking hydrophilic statin medications, the percentages of women who exercised at
moderate intensity in a typical month were stable at around 51% for the duration of
20
hydrophilic statin treatment up to and beyond two years. Regardless of the type of statin or
the CVD health status of the women, the proportion of women who exercised at moderate
intensity were similar across various time points within that group of women (stratified by
the lipophilicity of statin and by CVD status). Selection bias was not found because the
distributions of physical activity were similar across strata.
Table 1. Data availability in biennial NHANES, 1999-2000 to 2011-2012
20112012
Depression Instrument
instrument
PHQ9
modality
survey
Muscle strengthening activity (MSA)
no MSA
PAQ_G
MSA
none
Individual Activity
none
20092010
20072008
20052006
20032004
20012002
19992000
PHQ9
survey
PHQ9
survey
PHQ9
survey
WHO
interview
WHO
interview
WHO
interview
Exists
none
none
Exists
none
none
n/a
Exists
Exists
n/a
Exists
Exists
n/a
Exists
Exists
n/a
Exists
Exists
2.2 Assessment of Depression
During 1999-2006, depression severity was assessed using either personal
interviews or validated surveys. A long format of depression data was used in 1999-2004,
whereas a shortened format of depression data was implemented in and after 2005. During
1999-2000, 2001-2002, and 2003-2004, depression was assessed in person by trained
personnel during face-to-face private interviews in mobile examination centers (MEC)
across the USA. These depression data were recorded using the World Health Organization
Composite International Diagnostic Interview (CIQD) structure. During these three
biennial cycles, depressive symptoms were stored using the in-person interview data
21
structure of the WHO Composite International Diagnostic Interview (CIQD) questionnaire.
The depression survey was redesigned during 2005-2006. In and after 2005, depressive
symptoms were self-reported using the validated nine-item Patient Health Questionnaire
(PHQ9) survey. Depression was assessed using the 9 items survey known as the Patient
Health Questionnaire (PHQ or PHQ9).
Different sets of depression data were pooled to address different research
questions. The sample for muscle strengthening analysis (1999-2006) contained
individuals who participated in the long WHO depression interviews (from 1999 to 2004)
and individuals who completed the self-reported validated PHQ9 short survey (from 2005
to 2006). For the analysis of moderate intensity physical activity and duration of lipophilic
statins (1999-2012), the sample contained adults who participated in the WHO depression
interviews (from 1999 to 2004) and adults who completed the self-reported PHQ9 survey
(from 2005 to 2012).
In order to obtain sufficiently large sample cell sizes for analysis, we pooled the
CIQD depression data and the PHQ9 depression data. To merge data from various years,
we translated the CIQD personal interview data to the same scale as the PHQ9 survey data
by mapping corresponding items of these two instruments. We created a novel mapping
technique to convert depression data from the face-to-face WHO (World Health
Organization) Composite International Diagnostic Interview (CIQD) format into the selfreported depression Patient Health Questionnaire-9 (PHQ9) survey format. Combining
multiple years of data increased the sample sizes of various special interest subgroups. The
sample for the initial muscle strengthening research question contained 7,354 adults over
22
the age of 18 (consisting of 3,419 men and 3,995 women), who either participated in faceto-face depression interviews or completed the self-reported PHQ9 depression survey. To
further understand muscle strengthening activity in the younger generations, we examined
a subset of adults under the age of 50 consisting of 5,459 adults (2,445 men and 3,014
women). The sample for the “moderate intensity activity” analyses consisted of 10,460
adults (5,843 women and 4,617 men) at least eighteen years old. The sample for statin
analyses included 5,843 women and 4,552 men.
We created the following conversion method to translate the face-to-face clinical
assessment of depression to the subsequent self-reported assessment of depression. During
the 1999, 2001, and 2003 biennial NHANES, private in-person face-to-face interviews
took place in the mobile examination centers (MEC). Trained personnel of the MEC used
the Composite International Diagnostic Interview (CIQD) for depression containing over
112 questions. During the 2005, 2007, 2009, 2011 biennial NHANES surveys, the
assessment of depression was converted from interview format to “Patient Health
Questionnaire (PHQ9) survey format. The PHQ9 contained nine validated items that were
consistent with the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) signs
and symptoms for depression.”
Table 2 describes the computation of the frequency and binary values of each PHQ9
item from the in-person face-to-face interview data prefixed by “CIQD.” For example, the
first row or the first PHQ9 question was true if any of the in-person survey items CIQD006
or CIQD008 or CIQD030 or CIQD031 were true. The frequency of the first PHQ9 item (on
a scale of 0 to 3) was based on CIQD009 frequency and CIQD010 duration. The ordering
23
of the in-person CIQD interview question in each row carried no specific meaning. Each
row of Table 2 corresponds to a PHQ9 item, explaining how each PHQ9 item can be
computed from values stored in the corresponding CIQD interview questions.
Table 2. Mapping binary and frequency data from in person WHO interviews to PHQ9
survey
PHQ1
In-Person
In-Person
In-Person
In-Person
In-Person
Questions
Frequency
Duration
Questions
Questions
Questions
Questions
CIQD009
CIQD010
CIQD006
CIQD008
CIQD030
CIQD031
CIQD028
CIQD003
PHQ2
CIQD002
SED duration
CIQD001
PHQ3
CIQD026
n/a
CIQD025
CIQD027
PHQ4
CIQD015
CIQD016
CIQD005
CIQD012
PHQ5
# positives
n/a
CIQD019
CIQD020
CIQD022
CIQD023
PHQ6
CIQD036
n/a
CIQD036
CIQD037
CIQD040
CIQD041
PHQ7
# positives
n/a
CIQD043
CIQD044
CIQD045
CIQD046
PHQ8
# positives
n/a
CIQD032
CIQD033
CIQD034
CIQD035
PHQ9
# positives
n/a
CIQD047
CIQD048
CIQD049
CIQD050
096 <=
(1<=CIQD099
(1<=CIQD103
(1<=CIQD106=
360)
<=300)
<= 320)
=365)
CIQD042
(1<=CIQD
PHQ10
CIQD095
n/a
(CIQDPC)
Table 3 shows the specific language of the questions, and the details of how WHO
the in-person interview questions were mapped to each of the nine items of the PHQ9
survey. Detailed information of all the interview questions prefixed by CIQD are published
in the CDC NHANES website. If each row had at least one true “in-person question”, then
24
that corresponding PHQ9 item was true. The WHO frequency value was then subsequently
converted into the validated PHQ9 scale of 0 (not at all), 1 (several days), 2 (more than half
days), and 3 (nearly every day). If the frequency value stored “the number of positive
responses of in-person questions”, then the total number of affirmative responses to all
WHO “in-person questions” were used to compute how frequently (on a scale of 0, 1, 2, 3)
such PHQ9 item took place. For clarity, the subscript of PHQ9 was dropped in tables with
algebraic formulae and in the next paragraph.
The actual values in the 9 PHQ data fields were computed based on the frequency,
duration, and in-person question of the corresponding WHO interview responses. For the
first item of the survey (PHQ1), if frequency was "About Half the Days" or "Less than Half
the Days" and duration was "Less than half the days", then the PHQ1 scale frequency was
coded as 1. If frequency was "About Half the Days" and duration was “All Day Long” or
“Most of the day” or "About half the days", then the PHQ scale frequency was coded as 2.
If frequency was "Every Day" or "Nearly Every Day" or "Most Days", then the PHQ scale
frequency was coded as 3. Similarly, PHQ2 frequency was computed from frequency
CIQD2 and duration CIQD3. For PHQ3, the PHQ scale frequency was coded as 1 if
frequency trouble sleeping (CIQ026) was “less often”; the PHQ scale frequency was coded
as 2 if frequency trouble sleeping (CIQ026) was “nearly every night”; the PHQ scale
frequency was coded as 3 if frequency trouble sleeping (CIQ026) was “every night”. If all
the “in-person questions” were missing values for that specific PHQ item, then that PHQ
value was set to missing value. The order in which in-person interview question were listed
in Table 3 had no special meaning. All of the in-person interview questions were equally
25
important in computing the corresponding PHQ depression value, regardless of their
ordering. For some PHQ items, the frequency data were sufficient to convert WHO values
into the self-reported PHQ scale; for other PHQ items, the frequency and duration data
provided the information necessary to convert interview survey data into the PHQ scale.
Table 3. Details of mapping from in person WHO interviews to PHQ9 surveys
Yrs
1999
to
2004
1999
to
2004
1999
to
2004
1999
to
2004
1999
to
2004
1999
to
2004
1999
to
2004
1999
to
2004
1999
to
2004
PHQ9 description
WHO
CIQD006
CIQD008
CIQD030
CIQD031
1. Little interest or pleasure in
doing things
2. Feeling down, depressed, or
hopeless
CIQD001
3. Trouble falling or staying
asleep, or sleeping too much
CIQD025
CIQD027
CIQD028
CIQD005
CIQD012
4. Feeling tired or having little
energy
CIQD019
CIQD022
5. Poor appetite or overeating
CIQD036
CIQD043
CIQD044
CIQD045
CIQD046
CIQD032
CIQD033
CIQD034
CIQD035
CIQD047
CIQD048
CIQD049
CIQD050
6 Feeling bad about yourself or
that you are a failure or have let
yourself or your family down
7 Trouble concentrating on things,
such as reading the newspaper or
watching television
8 Moving or speaking so slowly
that other people could have
noticed. Or the opposite being so
fidgety or restless that you have
been moving around a lot more
than usual
9 Thoughts that you would be
better off dead, or of hurting
yourself
Continued
26
Table 3: continued
1<=CIQD096
<= 360 or
1<=CIQD099
<=300 or
1<=CIQD103
<=320 or
1<=
CIQD106<=365
or CIQDPC==1
1<=CIQD096
<= 365 or
1<=CIQD099
<=200 or
1<=CIQD103
<=365 or
1<=
CIQD106<=365
or CIQDPC==1
1<=CIQD096
<= 365 or
1<=CIQD099
<=265 or
1<=CIQD103
<=280 or
1<=
CIQD106<=365
or CIQDPC==1
Only
1999
to
2000
Only
2001
to
2002
Only
2003
to
2004
Only 1999-2000
(10) If you checked off
any problems, how
difficult have these
problems made it for you
to do your work, take care
of things at home, or get
along with other people?
have these problems
made it for you to do your
work, take care of things
at home, or get along with
other people?
Only 2001-2002
(10) If you checked off
any problems, how
difficult have these
problems made it for you
to do your work, take care
of things at home, or get
along with other people?
have these problems
made it for you to do your
work, take care of things
at home, or get along with
other people?
Only 2003-2004
(10) If you checked off
any problems, how
difficult have these
problems made it for you
to do your work, take care
of things at home, or get
along with other people?
have these problems
made it for you to do your
work, take care of things
at home, or get along with
other people?
From 1999 to 2003, the minimum and maximum values of certain data items were
time-variant and based on the year of publication in NHANES, as shown in the colored
boxes of Table 4. Although the overall mapping from WHO to PHQ9 was similar among
27
the various biennial years, the specific limiting values of certain fields varied by year, as
illustrated by the colored areas of Table 3. These colored boxes highlight the differences
in the delimiting values from year to year. The mapping from the WHO interview data to
the PHQ9 survey data takes into account these differences in limiting values, because the
actual limiting values of NHANES fields were modified depending on the year of data
collection.
Table 4. Time-varying field limitations
Yrs
1999
to
2004
1999
to
2004
1999
to
2004
1999
to
2004
1999
to
2004
1999
to
2004
1999
to
2004
1999
to
2004
1999
to
2004
PHQ9 description
WHO
CIQD006
CIQD008
CIQD030
CIQD031
1. Little interest or pleasure in
doing things
2. Feeling down, depressed, or
hopeless
CIQD001
3. Trouble falling or staying
asleep, or sleeping too much
CIQD025
CIQD027
CIQD028
CIQD005
CIQD012
4. Feeling tired or having little
energy
CIQD019
CIQD022
5. Poor appetite or overeating
CIQD036
CIQD043
CIQD044
CIQD045
CIQD046
CIQD032
CIQD033
CIQD034
CIQD035
CIQD047
CIQD048
CIQD049
CIQD050
6 Feeling bad about yourself or
that you are a failure or have let
yourself or your family down
7 Trouble concentrating on things,
such as reading the newspaper or
watching television
8 Moving or speaking so slowly
that other people could have
noticed. Or the opposite being so
fidgety or restless that you have
been moving around a lot more
than usual
9 Thoughts that you would be
better off dead, or of hurting
yourself
Continued
28
Table 4: continued
1<=CIQD096
<= 360 or
1<=CIQD099
<=300 or
1<=CIQD103
<=320 or
1<=
CIQD106<=365
or CIQDPC==1
1<=CIQD096
<= 365 or
1<=CIQD099
<=200 or
1<=CIQD103
<=365 or
1<=
CIQD106<=365
or CIQDPC==1
1<=CIQD096
<= 365 or
1<=CIQD099
<=265 or
1<=CIQD103
<=280 or
1<=
CIQD106<=365
or CIQDPC==1
Only
1999
to
2000
Only
2001
to
2002
Only
2003
to
2004
Only 1999-2000
(10) If you checked off
any problems, how
difficult have these
problems made it for you
to do your work, take care
of things at home, or get
along with other people?
have these problems
made it for you to do your
work, take care of things
at home, or get along with
other people?
Only 2001-2002
(10) If you checked off
any problems, how
difficult have these
problems made it for you
to do your work, take care
of things at home, or get
along with other people?
have these problems
made it for you to do your
work, take care of things
at home, or get along with
other people?
Only 2003-2004
(10) If you checked off
any problems, how
difficult have these
problems made it for you
to do your work, take care
of things at home, or get
along with other people?
have these problems
made it for you to do your
work, take care of things
at home, or get along with
other people?
After mapping the WHO depression interview data (1999 to 2003) into the PHQ9
format, the converted WHO interview data were then combined with the PHQ9 survey
data (2005). The total possible PHQ9 depressive scores ranged from 0 to 27, because each
29
of the nine PHQ9 questions spanned the possible values from zero to three. Each of the 9
questions in the validated PHQ9 survey had a scale of 0, 1, 2, and 3. Depression scores
were stratified using previously established clinical cut-points of 5, 10, 15, and 20, using
the guidelines proposed by Kroenke73: absence of depression (0–4), mild depression (5–
9), dysthymia or chronic persistent depressive disorder (10–14), moderate or moderatelysevere depression (15–19), major depression (20–27) 74. To create sufficiently large subcell counts for statistical analyses, the presence or absence of depression was
dichotomized at the PHQ9 threshold value of 10. All “refused to answer” responses to
PHQ9 questions were classified as missing values and they were removed from the
analysis using “complete case analysis.” No imputation was performed for missing data
throughout all analyses.
2.3 Assessment of muscle strengthening activity and aerobic activity (1999-2006)
Data on muscle strengthening activity were self-reported and available only from
1999-2000 to 2005-2006 in NHANES. No ‘muscle strengthening activity’ data were
available in and after 2007 due to modifications of the physical activity survey. The
aggregated data for muscle strengthening activity was assessed using the question coded
PAD440, which asked the participants about their muscle strengthening activity. Muscle
strengthening activity was assessed as a binary variable by asking whether the participants
performed “any physical activity designed to strengthen muscles such as lifting weights,
push-ups or sit-ups, over the past 30 days” 75, and by asking what specific leisure time
strength training activity they performed over the past 30 days76. Participants were asked
30
to include all muscle strengthening activity within the past 30 days. Many participants of
the final sample had missing muscle strengthening data values in the individual physical
activity files, but all participants of the final sample had non-missing valid self-reported
aggregated muscle strengthening data. Therefore, aggregated muscle strengthening data
were used.
Aerobic activity data were assessed using both aggregated physical activity data
files and individual physical activity data files, from 1999-2000 to 2005-2006. Aerobic
activity energy expenditure was computed as the sum of (i) the aerobic energy expenditure
from aggregated physical activity files and (ii) the aerobic energy expenditure from
individual physical activity files.
Aggregated aerobic activities were assessed by asking the participants whether they
“walked or biked over the past 30 days”. Self-reported aggregated physical activity
information contained the binary responses which described whether the participant
walked or biked or expended aerobic physical energy over a specific time period. In the
aggregated physical activity files (PAQ files), the frequency field “PAQ050Q” contained
the number of times walked or bicycled per day/week/month (converted to per month), and
the duration field “PAD080” contained the number of minutes performing such aerobic
activities per day (converted to hours per day). The intensity of aerobic activity energy
expenditure was conservatively estimated at 3 MET (Metabolic Equivalent of Task) in the
unit of kcal per kg per hour. The aerobic energy expenditure of self-reported aggregated
aerobics activity of walking or biking was computed as the product of intensity in MET,
converted frequency PAQ050Q, and converted duration PAD080.
31
Self-reported individual activity data consisted of the duration, frequency, intensity
MET (metabolic equivalent of task), and description of each physical activity such as
aerobic activities (dancing, swimming, etc.), and anaerobic activities (sit-ups or weightlifting)77. For all the aerobic activities found in the individual activity data file, the
corresponding frequency, duration, and intensity of each aerobic activity were multiplied
to compute the energy expenditure per kilogram body weight per month. The total aerobic
energy expenditure was calculated for each participant as the summation of energy
expenditures across all reported aerobic activities78.
For the separate categorical analysis of depression and the type of exercise
(anaerobic muscle strengthening activity versus aerobic) using the NHANES 1999-2006
data, we used the 2008 Physical Activity Guidelines for Americans (PAGA) published by
the U.S. Department of Health and Human Services to identify adults who met or exceeded
the recommended level of aerobic exercise (150 minutes per week of moderate intensity
exercise or 75 minutes per week of vigorous exercise or equivalent combinations of
moderate and rigorous exercise)79. The following four groups of adults included: (i) the
reference group, (ii) the aerobic only group that met or exceeded PAGA aerobics but lacked
muscle strengthening activity, (iii) the group that completed muscle strengthening activity
but did not meet PAGA aerobics guidelines, and (iv) the group that performed muscle
strengthening activity and aerobics activity at or above the guideline. The reference group
contained adults who did not meet the PAGA aerobics guideline and did not engage in
muscle strengthening activity.
32
2.4 Assessment of “moderately intense physical activity” using (NHANES 1999-2012)
NHANES used the phrases "moderate intensity activity", "moderate intensity
sports", “moderate intensity exercise” and "moderate activities" interchangeably to
describe physical activity or exercise performed at moderate intensity. NHANES included
all categories of “moderate intensity activities” performed for a wide range of purposes,
including but not limited to working, manual labor, commuting, fitness, exercising, and
recreation. Consistent with NHANES, the terms "moderate intensity exercise",
“moderately intense physical activity” and "moderate intensity activity" were used
synonymously to refer to the same concept of “physical activity or exercise” performed at
moderate intensity that "caused light sweating or slight to moderate increase in breathing
or heart rate for at least ten minutes continuously."
The survey for physical activity of NHANES underwent major structural
modifications in 2007. From 1999-2000 to 2005-2006, data on physical activity were
stored in two formats: (i) aggregated physical activity data files asked the participants about
their overall physical activity within specific time periods. (ii) Separate individual physical
activity data files enumerated the long list of various specific physical activity. However,
the survey was re-designed in 2007-2008 and a single source aggregated physical activity
survey was implemented that did not collect information on muscle strengthening activity
and removed the long detailed list of specific exercises and physical activities. The new
activity survey was re-designed to collect only aggregated physical activity data.
33
These physical activity survey modifications impacted the structure and format of
“moderate intensity activity” data. Although moderately intense physical activity data was
available during NHANES 1999-2012, the detailed data format for moderately intense
physical activity changed in and after 2007. Moderately intense physical activity data were
available in a long dual format (aggregated and individual) during the 1999-2006 cycles
and then in a shortened single format (aggregated) during subsequent 2007-2012 cycles.
Moderate intensity physical activity was based upon both aggregated activity and
individual activity between 1999 and 2006. An aggregate measure of moderately intense
physical activity was determined by the question coded PAD320. It asked “Over the past
30 days, did you do any moderate activity for at least 10 minutes that caused light sweating,
slight to moderate increase in breathing or heart rate? Moderately intense physical activity
examples included brisk walking, golf and dancing.” Due to the wording of these questions,
we do not know whether the moderately intense physical activity applied to stretching,
flexibility exercises, muscle strengthening, or aerobic activity. In the individual activity
data files from 1999-2006, participants reported their leisure time activity but many leisure
time activity fields contained missing values. Individual activity files provided the data for
the metabolic equivalent, frequency and duration of a long list of leisure time activities.
To assess “moderately intense physical activity” from 2007 to 2012, participants
were asked: “in a typical week, whether they walked, or bicycled, or engaged in moderate
intensity physical activity (e.g. brisk walking or carrying light loads) that caused small
increase in breathing or heart rate for at least 10 minutes continuously, for work or
recreation.” In and after 2007, participants were not asked to report individual physical
34
activity. Unlike the prior years, there was no question about the duration, frequency,
metabolic equivalent of task (MET) for a long list of various leisure time physical activity.
Moderately intense physical activity data before 2007 were than pooled with those after
2007 to maximize sub cell sizes. In the merged data set, the unit of month was the
conservative unit of time for “moderately intense physical activity” or “moderate intensity
activity.”
2.5 Assessment of Medical Conditions
Medical condition files stored the self-reported health condition and medical
history of the participants. From 1999 to 2012, the data formats of medical condition files
were similar but they contained slight variations in topics that did not directly relate to our
research. For example, gluten-free diet information was available only in 2009-2010 and
2011-2012 but unavailable in prior years. Lead poisoning test questions were asked before
and during 2003-2004. In and after 2005-2006, the medical condition survey did not ask
about the length of time since last lead poisoning test. Despite these minor differences, all
the medical condition surveys asked about major diseases, family history of diseases, and
disablement conditions. Medical condition data were designed to monitor the time trend of
major disease burden in US population.
Cancer of multiple varieties, CVD, and arthritis were the major diseases and
medical condition data of interest in our research. Using the NHANES data schema, CVD
included “congestive heart failure, coronary heart disease, angina/angina pectoris,
myocardial infarction, stroke” (ischemic or hemorrhagic stroke). The varieties of cancer in
35
the survey included “bladder cancer, blood cancer, bone cancer, brain cancer, breast
cancer, cervical cancer, colon cancer, esophageal cancer, gallbladder cancer, kidney
cancer, larynx windpipe cancer, leukemia cancer, liver cancer, lung cancer,
lymphoma/Hodgkin's disease cancer, melanoma cancer, mouth/tongue/lip cancer, nervous
system cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, nonmelanoma Skin cancer, skin cancer, soft tissue (muscle or fat) cancer, stomach cancer,
testicular cancer, thyroid cancer, and uterine cancer”. However, there were insufficient
number of adults diagnosed with many of these listed cancer. Only data of the cancer of
breast, cervical, uterine, prostate, colon, rectum, non-melanoma skin, and all skin cancer
could be included in sub group stratification analyses.
Rheumatoid Arthritis and Osteoarthritis were adjusted as medical conditions in the
regression analyses. Rheumatoid Arthritis was coded as the value of 1 in MCQ190 from
1999-2000 to 2007-2008, as the value of 1 in MCQ191 in 2009-2010, and as the value of
2 in MCQ195 from 2011-2012. Osteoarthritis was coded as the value of 2 in MCQ190
from 1999-2000 to 2007-2008, as the value of 2 in MCQ191 in 2009-2010, and as the value
of 1 in MCQ195 from 2011-2012. Our research of exercise and depression, and of its
interaction with prolonged lipophilic statin treatment, had adjusted medical conditions such
as cancer, cardiovascular disease, and arthritis.
2.6 Assessment of prescription medication treatment and duration
The formats of medication data were similar across the years. All the participants
indicated whether they took medication within the past month. Each participant
36
enumerated all their medications and the total number of prescription medicines. For each
medication, the generic drug code and the numbers of days taking that medication (or
duration) were recorded. The FDA Food and Drug Administration codes were stored in
earlier surveys (NHANES 1999-2000 and 2001-2002) but not available in later surveys.
Statins were classified by lipophilicity into two groups, the lipophilic statin and the
hydrophilic statin group. Lipophilic statins included the simvastatin, lovastatin,
atorvastatin, pitavastatin, and cerivastatin. The hydro-philic statins category included
fluvastatin, pravastatin, and rosuvastatin.
The class of corticosteroid medication consisted of prednisone, prednisolone,
cortisone, hydro-cortisone, methylprednisolone, Triamcinolone, dexamethasone, and
betamethasone. Cortisone included cortisone, cortisone acetate, fludrocortisone acetate.
Hydro-cortisone included hydrocortisone, hydrocortisone acetate, hydrocortisone valerate,
hydrocortisone with neomycin sulfate. Prednisolone included prednisolone, prednisolone
acetate, prednisolone acetate with sulfacetamide sodium, prednisolone sodium phosphate.
Methylprednisolone included methylprednisolone and methylprednisolone acetate. The
duration of each of the corticosteroid treatment was stored for all users.
2.7 Assessment of metabolic risk factor, metabolic syndrome and covariates
Clinical and laboratory measurements were categorized using established
guidelines. The National Cholesterol Education Program (NCEP) Third Adult Treatment
Panel (ATP III) 2001 definition80 of “metabolic syndrome” requires that any 3 of the 5
factors are present (abdominal obesity, high triglycerides, low HDL cholesterol, high blood
37
pressure, and elevated fasting glucose). The abdominal adiposity risk factor is defined as
waist circumference >40" in men and > 35" in women. The triglycerides risk factor is met
if triglyceride level ≥150mg/dL. The HDL cholesterol risk factor is defined as <40mg/dL
in men and <50mg/dL in women. The blood pressure risk factor is present when systolic
blood pressure ≥130mHg or diastolic blood pressure ≥85 mmHg. The fasting glucose risk
factor is met when glucose ≥110 mg/dL is present or diabetes is diagnosed.
NHANES provided continuous variables for metabolic syndrome and metabolic
risk factor. Continuous metabolic risk factor variables were converted into clinical risk
categorical variables. The demographic data source contained age, ethnicity, and gender
data. NHANES “trained health technicians to measure the waist circumference and to
collect body measurement data." Body mass index, height and weight data were stored in
the “body measures” data files. NHANES measured "triglycerides enzymatically in
serum using a series of coupled reactions." Serum cholesterol and HDL cholesterol were
available in aggregated files from 1999-2004, and were available in separate files in and
after 2005. Systolic and diastolic blood pressure were measured repeatedly by MEC
examiners. “After resting quietly in a sitting position for five minutes and determining the
maximum inflation level, three consecutive blood pressure readings are obtained. If a
blood pressure measurement is interrupted or incomplete, a fourth attempt may be
made81.” Up to 4 repeated measurements of blood pressure were taken for the participant
by trained personnel. NHANES measured the "fasting plasma glucose of participants in
the morning examination session only", using enzyme hexokinase method in laboratories.
38
Chapter 3 Data Analysis
All statistical analyses were stratified by gender and performed using STATA
software. The analyses of men were done separately from the analyses of women. Gender
was stratified and not adjusted, because the prevalence of depression in women had been
known to consistently exceed the prevalence of depression in men. Separating the statistical
analyses by gender helped to better illuminate the research questions of physical activity
and depression.
All depression data were converted into and stored as PHQ9 depression data. The
PHQ9 depression scores were categorized using the established clinical PHQ9 cut-off points
(5, 10, 15, and 20). These cut-off points have been validated to represent previously defined
depression severity. We used the published cut-off points of PHQ9 in order to comply with
clinically meaningful classification of depressive symptoms82. For sufficiently large cell
size count in subgroup statistical analyses, the presence of depression was also
dichotomized at the value of 10. A PHQ9 value equal or great than 10 indicated depression
while a PHQ9 value less than 10 was the reference group of none or mild depression. The
four severity levels of depression were used to investigate the existence of trend of the
severity level of depression; multinomial analyses could be used in subgroup analyses with
sufficient number of adults. Dichotomization of PHQ9 depression and binary logistic
regression were used when there were insufficient number of adults in subgroup analyses.
39
3.1 Muscle strengthening activity
A total of 7354 adults (3935 women and 3419 men) over the age of 18 had valid
non-missing “muscle strengthening activity” data, of which a subset of 5459 adults (3014
women and 2445 men) were under the age of 50. To investigate muscle strengthening
activity using NHANES 1999-2006 data, gender-stratified logistic regression models and
multinomial logistic regression models were used to estimate the adjusted odds ratios of
depression associated with anaerobic muscle strengthening activity and to compute the
corresponding 95% confidence intervals, while adjusting for aerobic activity energy
expenditure. Aerobic activity was a confounder for the association between depression and
muscle strengthening activity. Controlling for total aerobic activity was necessary to
delineate the independent association between muscle strengthening activity and
depression severity.
Logistic regression was used to analyze the odds ratio of anaerobic muscle
strengthening activity associated with depression (PHQ9  10), while adjusting for a
continuous covariate of aerobic energy expenditure measured in kilocalories per kilogram
of body weight per unit time. Other covariates were age, ethnicity, body mass index BMI,
and medical conditions including arthritis, any kind of cancer, and any kind of CVD. The
odds of muscle strengthening activity were compared between the depressed adults with
the non-depressed adults.
Multinomial logistic regression models were used to estimate the adjusted odds
ratios of mild depression (PHQ9 from 5 to 9), chronic low dysthymia depression (PHQ9
from 10 to 14), moderate depression (PHQ9 from 15 to 19), and major depression (PHQ9
40

20) associated with anaerobic muscle strengthening activity, while adjusting for a
continuous aerobic energy expenditure. Trend tests were performed to investigate whether
the dose response trend was significant, and whether the odds ratios of progressively worse
severity of depression exhibited significant declining patterns.
3.2 Moderately intense physical activity
There were 10460 adults (5843 women and 4617 men) with non-missing and valid
“moderately intense physical activity” and depression data. The odds of depression
associated with moderately intense physical activity were analyzed using binary or
multinomial logistic regression models (1999-2012) in men and women. In various strata
of age, gender, diseases (arthritis, CVD, cancer), multinomial logistic regression models
were used to compute the odds ratios of depression severity associated with moderately
intense physical activity, while controlling for age, BMI, medical condition such as CVD,
cancer, arthritis, corticosteroid, statins, total cholesterol, and HDL. Among various strata
of adults who had arthritis, cancer (of the breast, cervix, uterine, prostate, colon rectum,
non-melanoma, melanoma, or skin), or CVD, or metabolic syndromes, distinct and
separate multinomial logistic regression models were used to compute the adjusted odds
ratios of “moderate intensity activity” among adults with various severity level of
depression (mild, dysthymia, moderate, major depression). Trend tests investigated
whether the odds ratios of depression associated with moderately intense physical activity
had exhibited significant dose-response trends.
41
3.3 Metabolic risk factor, metabolic syndrome, and medical conditions
Subgroup multinomial logistic regression were performed to estimate the odds of
depression (i.e. the severity level of depression) associated with either anaerobic muscle
strengthening activity or associated with moderately intense physical activity. These
subgroups included adults diagnosed with arthritis, cancer (of the breast, cervix, uterine,
prostate, colon rectum, non-melanoma, melanoma, or skin), or cardiovascular conditions
(congestive heart failure, coronary heart disease, angina pectoris, myocardial infarction,
ischemic stroke, hemorrhagic stroke), or metabolic syndrome.
Logistic regression was used to estimate the odds ratios of depression associated
with different types of exercises: anaerobic muscle strengthening exercise, aerobic
exercise, and the combined regimen of both anaerobic and aerobic exercise. All adults were
partitioned into four groups: (i) the reference group of individuals that did not meet the
recommended threshold for aerobic exercise and did not perform muscle strengthening
activity, (ii) individuals that met or exceeded the aerobic recommendation but did not
perform strength training, (iii) the strength training group that did not meet the aerobic
recommendation, and (iv) the group that met the aerobic recommendation and also
performed strength training. Gender-specific odds ratios were also adjusted for age,
ethnicity, BMI, and the presence of disabling medical conditions including any kind of
CVD, any type of cancer, and arthritis.
Using the NCEP criteria of metabolic syndromes in separate analyses, multiple
separate t tests were used to compare the adults with metabolic syndromes (at least 3 risk
factors) to the adults without metabolic syndromes (less than 3 risk factors) in the
42
prevalence of depression severity, muscle strengthening activity, and moderately intense
physical activity. Among adults with metabolic syndromes or metabolic risk factor, logistic
regression was used to examine the relationship between moderately intense physical
activity and depression severity, as well as anaerobic muscle strengthening activity and
depression.
For the association between statin use and depression using NHANES 1999-2012
data, analysis of variance (ANOVA) and adjusted logistic regression models were used to
examine statin medication data and depression stratified by gender. Using logistic
regression models with stratification by gender and CVD, the adjusted odds ratios of
depression were estimated for lipophilic statins (Simvastatin, Lovastatin, Cerivastatin,
Atorvastatin, Pitavastatin), hydrophilic statins (Fluvastatin, Pravastatin, Rosuvastatin), and
corticosteroids, while controlling for physical activity, age, body mass index, total
cholesterol, high density lipoprotein cholesterol, and medical conditions such as arthritis,
cancer. Logistic regression models were used to compute and to plot the time series graphs
of the odds ratios of depression associated with moderate intensity exercise, within various
strata of CVD, lipophilic and hydrophilic medications. The stratification by gender and
cardiovascular disease delineated the association between depression and moderate
intensity exercise over the time durations of lipophilic statin treatment.
43
Chapter 4 Results: muscle strengthening activity and depression, 1999 to 2006
Anaerobic muscle strengthening activity showed a significant independent inverse
association with depression, even after adjusting for aerobic activity. In all age categories
(< 50 years old, and  18 years old), the prevalence of depression was higher in women
than men, and muscle strengthening activity was more popular in men than women. Among
women over the age of 18 and men over 18 years of age, the odds of dichotomized
depression (PHQ9  10) was inversely and significantly associated with muscle
strengthening activity. These inverse associations between muscle strengthening activity
and depression (PHQ9  10) were significant in men over 18 years old, in women over 18
years old, in women under 50 years old, but not in men under 50 years old. The odds ratios
of muscle strengthening activity associated with the severity level of depression (mild,
dysthymia, moderate and major depression) demonstrated a consistent and significant
declining trend in both men and women. Muscle strengthening activity was inversely
associated with the severity level of depression, while adjusting for aerobic activity, age,
body mass index, and medical conditions such as CVD, arthritis, and cancer.
Among adults under 50 years old, men had higher prevalence of muscle
strengthening activity, higher aerobic energy expenditure (kilocalories/kilogram body
mass /month), lower prevalence of depression, lower prevalence of obesity, and lower
prevalence of medical conditions (including arthritis, cancer, CVD) than women. The
44
sample of adults under fifty contained 5,459 adults (consisting of 3,014 women and 2,445
men) under the age of 50 (Table 5). The age distribution (about half under 30 years old,
and about one-third from 30 to 40 years old) and ethnicity distribution (about 40% white
and 22% African American) were similar among men and women. However, more
women were “classified as obese” than men (33.6% versus 28%) and more women
reported a medical history of arthritis, cancer or CVD than men (11.7% versus 7.5%).
Women under 50 were less likely to report muscle strengthening activity than men
(26.5% versus 41%, with t-test p<0.0001); furthermore, women had a higher prevalence
of dichotomized depression (8.8% versus 5.7% with PHQ9 score of 10 or more, p<0.001).
Using clinically established depression levels defined by Kroenke83, the prevalence levels
of mild, (chronic persistent) dysthymia and merged moderate-major depression among
women were 10.9%, 6.2%, and 2.8%, respectively whereas the corresponding levels
among men were 9%, 4.1%, and 1.6% (p<0.001). Men had lower prevalence of all
severity levels of depression than women.
The gender differences in all adults over 18 years of age were similar to the gender
differences in adults under 50 years old with the exception of cardiovascular medical
condition. In adults over 18 years old, men had higher prevalence of CVD than women; in
contrast, among adults under 50 years old, men had lower prevalence of CVD than women.
In all the adults over 18 years old, men had higher prevalence of muscle strengthening
activity, higher aerobic energy expenditure, higher prevalence of CVD, lower prevalence
of depression, lower prevalence of obesity, lower prevalence of arthritis and cancer than
women, even though both men and women had similar age and ethnicity distributions. The
45
entire sample of adults over the age of 18 years old consisted of 7,354 adults, including
3,935 women and 3,419 men (Table 6). Men and women had similar distribution of age
and ethnicity. More women (35.3%) were identified “as obese” than men (28.6%). More
women had a medical history of arthritis (18% versus 15%), cancer (5.5% versus 4.6%)
than men, whereas more men had a medical history of CVD (7.8% versus 5.2%) than
women. More men reported muscle strengthening activity than women (35.3% versus
24.8%). Women had higher prevalence of mild depression (12.3%), chronic persistent
dysthymia (5.7%) and merged moderate-major depression (2.6%) than men (p<0.01). In
men, the prevalence of mild depression, chronic persistent dysthymia and merged
moderate-major depression were 9.4%, 4%, 1.6% respectively. Similarly, the prevalence
of dichotomized depression (PHQ9  10) were higher in women than men (8.4% women
versus 5.7% men, with p<0.01). All severity levels of depression were more common in
women and muscle strengthening activity was more popular in men.
We hypothesized that the inverse dose-response between the severity levels of
depression and anaerobic muscle strengthening activity would be evident in all age
categories, as well as in both men and women. Gender, age, and aerobic activity were
included in regression models as potential confounders. To delineate the linkage between
depression severity and predominantly anaerobic muscle strengthening activity, separate
logistic or multinomial analyses were stratified by gender and adjusted for aerobic activity.
46
Table 5. Descriptive statistics of adults < 50 years of age: NHANES 1999-2006
Characteristics
Female (n=3014)
Age (years)
under 30
30 to under 40
40 to under 50
1569
1069
376
(52.0%)
(35.5%)
(12.5%)
1179
902
364
(48.2%)
(36.9%)
(14.9%)
2748
1971
740
(50.3%)
(36.1%)
(13.6%)
59
1941
1014
(2.0%)
(64.4%)
(33.6%)
57
1716
672
(2%)
(70%)
(28%)
116
3657
1686
(2%)
(67%)
(31%)
1296
661
1057
(43%)
(22%)
(35%)
1022
578
845
(41.8%)
(23.6%)
(34.6%)
2318
1239
1902
(42.5%)
(22.7%)
(34.8%)
230
74
48
2662
(7.6%)
(2.5%)
(1.6%)
(88.3%)
136
18
30
2261
(5.6%)
(0.7%)
(1.2%)
(92.5%)
366
92
78
4923
(6.7%)
(1.7%)
(1.4%)
(90.2%)
800
2214
(26.5%)
(73.5%)
1003
1442
(41%)
(59%)
1803
3656
(33%)
(67%)
(64 to 75) 122.7
(113 to 132)
93.5
BMI (kg/(m2))
Missing
Not obese (BMI < 30)
Obese (BMI ≥ 30)
Ethnicity
Non-Hispanic White
African American
Other
Medical conditions
Arthritis
Cancer
Cardiovascular diseases
No major disease
Muscle Strengthening
Activity (MSA)
MSA
no MSA
(mean, range)
Aerobic activity
(kcal/kg/month)a
Depression
0 to 4 None
5 to 9 Mild
10 to 14 Dysthymia
15+ Moderate & Major
Dichotomized PHQ9
Total (n=5459)
2418
329
187
80
(80.1%)
(10.9%)
(6.2%)
(2.8%)
2085
221
100
39
(85.3%)
(9%)
(4.1%)
(1.6%)
4503
550
287
119
(82.5%)
(10%)
(5.3%)
(2.2%)
267
(8.8%)
139
(5.7%)
406
(7.4%)
2747
(91.2%)
(PHQ9 < 10 )
Means for aerobic energy expenditure.
2306
(94.3%)
5043
(92.6%)
(PHQ9 ≥ 10 )
a
69.8
Male (n=2445)
47
Table 6. Descriptive statistics for all adults  18 years old: NHANES 1999-2006
Characteristics
Age (years)
under 30
30 to under 40
40 + plus
Female
(n=3935)
Male
(n=3419)
Total
(n=7354)
1569
1069
1297
(39.9%)
(27.1%)
(33%)
1179
902
1338
(34.5%)
(26.4%)
(39.1%)
2748
1971
2635
(37.4%)
(26.8%)
(35.8%)
71
2476
1388
(1.8%)
(62.9%)
(35.3%)
74
2366
979
(2.1%)
(69.2%)
(28.6%)
145
4842
2367
(2%)
(65.8%)
(35.2%)
1829
870
1236
(46.5%)
(22.1%)
(31.4%)
1612
789
1018
(47.1%)
(23.1%)
(29.8%)
3441
1659
2254
(46.8%)
(22.6%)
(30.6%)
707
215
206
2807
(18%)
(5.5%)
(5.2%)
(71.3%)
514
157
267
2481
(15%)
(4.6%)
(7.8%)
(72.6%)
1221
372
473
5288
(16.6%)
(5.1%)
(6.4%)
(71.9%)
978
2957
(24.8%)
(75.2%)
1208
2211
(35.3%)
(64.7%)
2186
5168
(29.7%)
(70.3%)
63.3 (59 to 67)
105.2 (98 to 112)
82.8
3120
485
226
104
(79.4%)
(12.3%)
(5.7%)
(2.6%)
2903
320
139
57
(85%)
(9.4%)
(4%)
(1.6%)
6023
805
365
161
(81.9%)
(10.9%)
(5%)
(2.2%)
330
(8.4%)
196
(5.7%)
526
(7.2%)
3605
(91.6%)
(PHQ9 < 10 )
a
Means for aerobic energy expenditure.
3223
(94.3%)
6828
(92.8%)
BMI (kg/(m2))
Missing
Not obese (BMI < 30)
Obese (BMI ≥ 30)
Ethnicity
Non-Hispanic White
African American
Other
Medical conditions
Arthritis
Cancer
Cardiovascular diseases
No major disease
Muscle Strengthening
Activity (MSA)
MSA
no MSA
(mean, range)
Aerobic activity
(kcal/kg/month) a
Depression
0 to 4 None
5 to 9 Mild
10 to 14 Dysthymia
15+ Moderate & Major
Dichotomized Depression
(PHQ9 ≥ 10 )
48
In the subgroups of men and women under 50 years of age, there were inverse
associations between depression (PHQ9  10) and anaerobic muscle strengthening activity,
after adjusting for aerobic activity energy expenditure, age, body mass index (BMI), and
diagnosed medical conditions including arthritis, CVD, cancer (Table 7). Odds ratios were
statistically significant for women and approached significance in men. In the fully
adjusted model, depressed women (PHQ9  10) had significantly lower odds of anaerobic
muscle strengthening activity (OR=0.58, 95% CI = 0.41 to 0.82) than non- depressed
women. The corresponding point estimate for men was suggestive of an inverse association
but did not reach statistical significance (OR=0.79, 95% CI=0.54 to 1.1). Both crude and
adjusted models yielded similar estimates of the odds ratios of anaerobic muscle
strengthening activity.
For both men and women over the age of 18, depression (PHQ9  10) was
significantly and inversely associated with muscle strengthening activity, after adjusting
for aerobic energy expenditure, age, BMI, and diagnosed arthritis, CVD, cancer, as
supported by the results of logistic regression models in (Table 8). In the fully adjusted
model, depressed women had a significantly lower odds of performing anaerobic muscle
strengthening activity than non-depressed women (OR=0.59, 95% CI = 0.43 to 0.8). In
men over 18 years old, anaerobic muscle strengthening activity was inversely associated
with depression (OR=0.66, 95% CI=0.47 to 0.93). Crude and adjusted models produced
similar results, supporting the conclusion that depression (PHQ9  10) was inversely
associated with anaerobic muscle strengthening activity.
49
Table 7. Gender-stratified Odds ratios of depression (PHQ9≥10) associated with muscle
strengthening activity for adults under 50 years of age: NHANES 1999-2006
Nondepressed
Depressed
Adjusted
Odds
Ratios*
(OR)
None
1997
217
1
Reference
Yes
750
50
0.58
(0.41,
Muscle strengthening
activity in adults <50
years old
OR 95% CI
Women (n=3014)
0.82)
Men (n=2445)
None
1352
90
1
Reference
Yes
954
49
0.79
(0.54,
1.1)
* Adjusted for age, aerobic energy expenditure, BMI, ethnicity, and medical condition
(CVD, cancer, arthritis).
Table 8. Gender-stratified Odds ratios of depression (PHQ9≥10) associated with muscle
strengthening activity for all adults  18 years of age: NHANES 1999-2006
Adjusted
Muscle strengthening NonOdds
OR
activity in all adults
depressed Depressed Ratios*
95% CI
(OR)
Women (n=3935)
None
2670
272
1
Reference
Yes
935
58
0.59
(0.43,
0.8)
Men (n=3419)
None
2051
140
1
Reference
Yes
1172
56
0.66
(0.47,
0.93)
* Adjusted for age, aerobic energy expenditure, BMI, ethnicity, and medical condition
(CVD, cancer, arthritis).
50
Gender-stratified multinomial logistic regression models were used to examine the
dose response patterns between the severity level of depression (mild, dysthymia,
moderate, major depression) and anaerobic muscle strengthening activity, while adjusting
for aerobic physical activity. The odds ratios of performing muscle strengthening activity
decreased as the severity of depression level exacerbated from mild to major depression,
while adjusting for aerobic activity energy expenditure, age, BMI, ethnicity, and medical
conditions (CVD, cancer, arthritis). Adults with major depression had lower odds of
performing muscle strengthening activity than adults with mild depression.
In women, the severity level of depression was inversely related to muscle
strengthening activity (Table 9). Among women under the age of 50, the odds ratios of
mild depression, chronic dysthymia, moderate depression, and major depression associated
with muscle strengthening activity dropped through 0.99, 0.61, 0.59, to 0.26, respectively.
Similarly, in all the women who were at least 18 years of age, the odds ratios of mild
depression, chronic dysthymia, moderate depression, and major depression associated with
muscle strengthening activity declined through 0.95, 0.58, 0.65, to 0.42, respectively.
Although the point estimates supported inverse association between depression and muscle
strengthening activity, the corresponding confidence intervals were wide. Results from
non-parametric trend tests showed the significant decline of the estimated odds ratios of
depression severity associated with anaerobic muscle strengthening activity in women
under 50 years old (p<0.01) and in women over 18 years of age (p<0.01).
In men, multinomial logistic regression was used to analyze merged data that had
combined several depression severity levels due to the low number of men with moderate
51
and major depression. Depression PHQ9 score at or above 10 were merged to form a single
category of “combined Dysthymia-Moderate-Major” severity level because there were
insufficient number of men under 50 years of age with moderate and major depression. In
men at least 18 years old, the odds ratios of mild depression, and “combined DysthymiaModerate-Major” associated with muscle strengthening activity were 0.93, and 0.64,
respectively.
As the severity level of depression worsened, the dose response trend of the odds
ratios of depression associated with muscle strengthening activity was found to be
declining in all strata of age and medical conditions. This declining trend was consistent in
age-stratified women (Figure 1), age-stratified men (Figure 2), disease-stratified women
(Figure 3), and disease-stratified men (Figure 4). Adults with major depression had lower
odds ratios of performing anaerobic muscle strengthening activity than adults with mild
depression.
The results of all non-parametric trend tests are consistent across age and gender
categories. As the severity level of depression exacerbated, the odds ratios of progressively
worse depression severity associated with muscle strengthening activity were declining
significantly (p<0.01), regardless of age, gender and disease stratification. The results of
non-parametric trend tests supported the significantly declining odds ratios of depression
associated with muscle strengthening activity. In women under 50 years old, muscle
strengthening activity was inversely related to mild depression (OR=0.99), dysthymia
(OR=0.61), moderate depression (OR=0.59), and major depression (OR=0.26). In men
who were at least 18 years old, the odds ratios of muscle strengthening activity for mild
52
depression and dichotomized depression were 0.93, 0.64, respectively. The trend of the
odds ratios of muscle strengthening activity was consistently and significantly dropping
through the severity level of depression, in all gender and age strata (i.e. women aged under
50, in women aged at least 18, in men under 50, and in men aged at least 18).
The strata of adults without CVD and the strata of adults free of both CVD and
arthritis were separately analyzed to study the dose response between depression severity
and muscle strengthening activity among adults free of debilitating diseases. In women
without CVD, the odds ratios of mild, chronic dysthymia, moderate, and major depression
associated with muscle strengthening activity were declining. Similar declining trend was
found in men without CVD. The odds ratio of muscle strengthening activity associated
with depression among men free of CVD and free of arthritis were consistently lower than
that odds ratio in men free only of CVD.
Similarly, the trend of the odds ratios of depression severity associated with muscle
strengthening activity was also found to be declining in CVD stratification analyses (i.e.
strata of adults without CVD; strata of adults free of both CVD and arthritis) (Table 10).
In women without CVD, the odds ratio of “muscle strengthening activity” among women
with mild, dysthymia, moderate, major depression were 0.98, 0.61, 0.61, 0.45, respectively;
similarly, in women free of both CVD and arthritis, the odds ratio of “muscle strengthening
activity” among women with mild, dysthymia, moderate, major depression were 0.95, 0.55,
0.66, and 0.29, respectively. Although the point estimates supported inverse association
between depression and muscle strengthening activity, the confidence intervals were wide.
53
Within the same level of depression severity, men free of both CVD and arthritis
had lower odds ratios than the corresponding men without CVD alone. The odds ratios of
mild depression associated with muscle strengthening activity (OR=0.95) among men free
of both arthritis and CVD were lower than that (OR=0.98) among men without CVD alone.
The odds ratios of dysthymia associated with muscle strengthening activity (OR=0.55)
among men free of both arthritis and CVD were lower than that corresponding odds ratios
of dysthymia associated with muscle strengthening activity (OR=0.71) among men without
CVD alone. The odds ratios of combined moderate-major depression associated with
muscle strengthening activity (OR=0.6) among men free of both arthritis and CVD were
lower than that corresponding odds ratios of combined moderate-major depression
associated with muscle strengthening activity (OR=0.74) among men without CVD alone.
Men with fewer debilitating diseases or medical condition (free of both arthritis and CVD)
had lower estimated odds of depression associated with “muscle strengthening activity”
than men with more medical condition (free of CVD alone). Dose response between
depression severity and muscle strengthening activity was found to be significantly
declining in adults without CVD, as well as in adults with CVD and arthritis.
54
Table 9. Odds ratios of depression severity (mild, dysthymia, moderate, major) and muscle
strengthening activity, stratified by age and gender: NHANES 1999-2006
Muscle
strengthening
activity
Adjusted
Odds
Ratios*
(OR)
OR 95% CI
Women
None
Mild
Dysthymia
Women Aged < 50
(n=3014)
1 Reference
0.99
(0.8, 1.2)
0.61
(0.4, 0.9)
Moderate
0.59
Major
Men
(0.3, 1.1)
0.26
(0.04, 2.0)
Trend test p< 0.001, Z=-50
Men Aged < 50 (n=2445)
None
1 Reference
mild
1.02
(0.7, 1.3)
Dysthymia0.77
(0.5, 1.1)
ModerateMajor
Combined
Trend test p<0.01 , Z=-7
Adjusted
Odds
Ratios*
(OR)
OR 95% CI
All women >=18 years
(n=3935)
1 Reference
0.95
(0.8, 1.2)
0.58
(0.4, 0.8)
0.65
(0.3, 1.1)
0.42
(0.1, 1.8)
Trend test p< 0.001, Z=-56
All men >=18 years (n=3419)
1 Reference
0.93
(0.7, 1.2)
0.64
(0.4, 0.90)
Trend test p< 0.001, Z=-53
* Adjusted for age, aerobic energy expenditure, BMI, ethnicity, and medical condition
(CVD, cancer, arthritis).
55
Table 10. Odds ratios of depression severity (mild, dysthymia, moderate, major) and
muscle strengthening activity, stratified by gender, and absence of CVD/arthritis:
NHANES 1999-2006
Muscle
Adjusted Odds
strengthening Ratios* (OR)
activity
Women
None
Mild
OR 95% CI
No CVD
n=3665
1 Reference
0.98
(0.7, 1.2)
Adjusted
Odds
Ratios
(OR)**
OR 95% CI
No CVD & No Arthritis
n=3099
1
Reference
0.95
(0.73,
1.2)
Dysthymia
0.61
(0.4, 0.8)
0.55
(0.35,
0.8)
Moderate
0.61
(0.3, 1.1)
0.66
(0.34,
Major
0.45
(0.1, 2.0)
0.29
(0.03,
1.2)
Trend test non-parametric p< 0.001, Z=-51
No CVD
Men
n=3089
None
1 Reference
2.4)
Trend test p< 0.001, Z=-56
No CVD & No Arthritis
n=2714
1
Reference
mild
0.98
(0.75, 1.27)
0.95
(0.73, 1.2)
dysthymia
0.71
(0.46, 1.06)
0.55
(0.35, 0.8)
ModerateMajor
Combined
0.74
(0.39, 1.41)
0.60
(0.32, 1.1)
Trend test non-parametric p< 0.001, Z=-48
Trend test p< 0.001, Z= -47
* Adjusted for age, aerobic energy expenditure, BMI, ethnicity, and medical condition
(arthritis, cancer)
** Adjusted for age, aerobic energy expenditure, BMI, ethnicity, and cancer medical
condition
56
Figure 1. Odds ratios of depression severity associated with muscle strengthening activity
in women stratified by age: NHANES 1999-2006
Age-stratified Women: Odds ratios of depression severity among
Muscle strengthening activity
Odds Ratios of Depresison
1.20
1.00
0.80
0.60
0.40
0.20
0.00
Mild
Dysthymia
Women Aged < 50
Moderate
Major
All women >=18 years old
Figure 2. Odds ratios of depression severity associated with muscle strengthening activity
in men stratified by age: NHANES 1999-2006
Age-stratified Men: Odds ratios of depression severity among
Muscle strengthening activity
Odds Ratios of Depresison
1.2
1
0.8
0.6
0.4
0.2
0
mild
Men Aged < 50
PHQ>=10
All men >=18 years old
57
Figure 3. Odds ratios of depression severity associated with muscle strengthening activity
among women without CVD or arthritis: NHANES 1999-2006
Disease-stratified Women: Odds ratios of depression
severity among Muscle strengthening women
Odds Ratios of Depresison
1.20
1.00
0.80
0.60
0.40
0.20
0.00
Mild
Dysthymia
Women: No CVD
Moderate
Major
Women: No CVD & No Arthritis
Figure 4. Odds ratios of depression severity associated with muscle strengthening activity
among men without CVD or arthritis: NHANES 1999-2006
Disease-stratified Men: Odds ratios of depression severity among
Muscle strengthening men
Odds Ratios of Depresison
1.2
1
0.8
0.6
0.4
0.2
0
mild
Men: No CVD
dysthymia
Moderate-Major Combined
Men: No CVD & No Arthritis
58
In the next analysis, logistic regression was used to analyze the odds of depression
associated with these three types of physical activity: (i) aerobic exercise alone, (ii)
anaerobic exercise alone, and (iii) combined regimen (consisting of both aerobic and
anaerobic exercises). Adults were partitioned into four exercise groups: (i) the reference
group, (ii) the aerobic only group that met or exceeded PAGA aerobic guidelines but lacked
muscle strengthening activity, (iii) the group that completed muscle strengthening activity
but did not meet PAGA aerobic guidelines, and (iv) the group that performed both muscle
strengthening activity and aerobic activity at or above the PAGA guideline.
Depression (PHQ9  10) was inversely associated with different types of physical
activity (e.g. aerobic, anaerobic, and combined regimens) in adults under 50 years of age
as well as all adults over 18 years of age. All logistic regression models controlled for age,
body mass index, ethnicity, CVD, arthritis, and cancer. Among women under 50 years of
age, the odds ratios of depression associated with aerobic exercise, anaerobic exercise, and
the combined regimen were 0.54, 0.57, and 0.52, respectively. Among men under 50 years
of age, the odds ratios of depression associated with aerobic exercise, anaerobic exercise,
and the combined regimen were 0.64, 0.83, and 0.61 (Table 11). Although all types of
physical activity were associated with lower odds of depression, the estimations reached
statistical significance in women but not in men
Similarly, all adults over the age of 18 were partitioned into these same four
exercise groups (reference, aerobic exercise only, anaerobic muscle strengthening activity
only, and combined regimen) for the purpose of computing the odds ratios of depression
(PHQ9  10) associated with these various types of exercise. In all adult women over 18
59
years of age, the odds ratios of depression (PHQ9  10) associated with aerobic exercise,
anaerobic exercise, and the combined regimen were 0.62, 0.66, and 0.49, respectively; in
all adult men over 18 years of age, the odds ratios of depression (PHQ9  10) associated
with aerobic exercise, anaerobic exercise, and the combined regimen were 0.39, 0.79, and
0.38, respectively (Table 12), while controlling for age, body mass index, ethnicity, CVD,
arthritis, and cancer. The observed odds ratios of each type of exercise (aerobic, anaerobic,
combined regimen) were statistically significant in comparing depressed women with nondepressed women; whereas only aerobic exercise and the combined regimen showed
significance in comparing depressed men with non-depressed men.
60
Table 11. Odds ratios of depression (PHQ9 ≥ 10) by exercise types in adults under 50
years of age: NHANES 1999-2006
Types of Exercise b
Women (n=3014)
Reference
Aerobic exercise only
Muscle strengthening only
Combined regimen
# Nondepressed
(PHQ9 < 10 )
# Depressed
(PHQ9 ≥
10 )
Odds
Ratio a
(OR)
1502
495
249
501
186
31
18
32
1
0.54
0.57
0.52
(0.36, 0.79)
(0.34, 0.96)
(0.35, 0.77)
1031
321
417
537
75
15
25
24
1
0.64
0.83
0.61
(0.35, 1.1)
(0.52, 1.3)
(0.37, 1.01)
Men (n=2445)
Reference
Aerobic exercise only
Muscle strengthening only
Combined regimen
95% CI
The odds ratios a of depression were estimated by exercise types b in adults under 50 years
of age: NHANES1999-2006.
a
The gender-stratified models were adjusted for age, BMI, ethnicity, medical
condition (CVD, cancer, arthritis).
b
Adults were partitioned into 4 groups of exercise types. The group of “aerobic
exercise only” included all adults who met or exceeded the PAGA guideline for aerobic
activity. The reference group included all adults who did not perform muscle
strengthening activity and did not meet the PAGA guideline for aerobic activity.
61
Table 12. Odds ratios of depression (PHQ9 ≥ 10) by exercise types in adults  18 years of
age: NHANES 1999-2006
Types of Exercise b
Women (n=3935)
Reference
Aerobic exercise only
Muscle strengthening
only
Combined regimen
# Non#
depressed Depressed
(PHQ9 < (PHQ9 ≥
10 )
10 )
Men (n=3419)
Reference
Aerobic exercise only
Muscle strengthening
only
Combined regimen
a
Odds
Ratio
(OR) a
95% CI
2221
449
429
242
30
30
1
0.628
0.666
(0.43, 0.93)
(0.44, 0.99)
506
28
0.498
(0.33, 0.75)
1564
487
490
124
16
33
1
0.391
0.798
(0.22, 0.66)
(0.53, 1.19)
682
23
0.385
(0.23, 0.62)
The gender-stratified models were adjusted for age, BMI, ethnicity, medical
condition (CVD, cancer, arthritis).
b
Adults were partitioned into 4 groups of exercise types. The group of “aerobic
exercise only” included all adults who met or exceeded the PAGA guideline for aerobic
activity. The reference group included all adults who did not perform muscle
strengthening activity and did not meet the PAGA guideline for aerobic activity.
62
Chapter 5 Results: moderately intense physical activity and depression, 1999 to 2012
Women had higher prevalence of all severity levels of depression and a lower
level of moderately intense physical activity than men. Age distributions were similar
between men and women. For adults under 50 years of age, men reported a higher
prevalence of cancer whereas for adults over 50, women reported a higher prevalence of
cancer. Men had a higher prevalence of CVD and reported higher usage of all types of
cholesterol lowering statin medications than women.
5.1 Characteristics of all adults
The prevalence of all severity levels of depression were consistently higher in
women, while more men reported exercising at moderate intensity in a typical month
(Table 13). The prevalence of mild, dysthymia, moderate, and major depression in men
were 13.7%, 5%, 2%, and 1%, respectively, whereas the prevalence of these depression
severity levels in women were 17.8%, 7.4%, 3.7%, and 1.4%, respectively. More men were
over 50 years old than women (66.3% versus 56%). Men had a higher prevalence of cancer
(14% in men versus 11.8% in women), whereas women had a higher prevalence of arthritis
(39% in women versus 34.2% in men). Although a higher proportion of women were
classified as obese (42.5% women versus 38.6% men), the prevalence of CVD in men was
almost double the prevalence of CVD in women (20.1% versus 11.3%). Higher percentages
63
of men were taking a lipophilic statin or a hydrophilic statin than women. The distribution
of ethnicity was similar between men and women.
Table 13. Descriptive statistics of moderately intense activity and other selected
characteristics among all adults: NHANES 1999-2012
Characteristics
Age (years)
under 30
30 to 50
50+
male
(n=4617)
female
(n=5843)
Total
(n=10460)
433 9.4% 932 16.0% 1365 13.0%
1122 24.3% 1640 28.1% 2762 26.4%
3062 66.3% 3271 56.0% 6333 60.5%
BMI (kg/(m2))
Not obese (BMI < 30)
2836 61.4% 3360 57.5%
Obese (BMI ≥ 30)
1781 38.6% 2483 42.5%
Ethnicity
Non-Hispanic White
2647 57.3% 3152 53.9%
African American
865 18.7% 1181 20.2%
Other
1105 23.9% 1510 25.8%
Medical conditions (same adult may have multiple diseases)
Arthritis
1580 34.2% 2276 39.0%
Cancer
646 14.0% 689 11.8%
Cardiovascular diseases
930 20.1% 661 11.3%
No CVD, No Arthritis, No
2322 50.3% 3103 53.1%
Cancer
Moderate Intensity Activity
(MIA)
no MIA
1704 36.9% 2350 40.2%
MIA
2913 63.1% 3493 59.8%
6196 59.2%
4264 40.8%
5799 55.4%
2046 19.6%
2615 25.0%
3856
1335
1591
5425
36.9%
12.8%
15.2%
51.9%
4054 38.8%
6406 61.2%
Continued
64
Table 13: continued
Statins
Simvastatin
753 16.3%
613 10.5% 1366 13.1%
Lovastatin
159
3.4%
125
2.1%
284
2.7%
Cerivastatin
Atorvastatin
Pitavastatin
Fluvastatin
Pravastatin
Rosuvastatin
n/a
456
1
9
126
121
n/a
9.9%
0.0%
0.2%
2.7%
2.6%
n/a
399
2
4
129
125
n/a
6.8%
0.0%
0.1%
2.2%
2.1%
n/a
855
3
13
255
246
n/a
8.2%
0.0%
0.1%
2.4%
2.4%
Depression
0 to 4 None
5 to 9 Mild
10 to 14 Dysthymia
15 to 19 Moderate
20+ Major
3621 78.4% 4072 69.7% 7693 73.5%
631 13.7% 1038 17.8% 1669 16.0%
229 5.0% 434 7.4% 663 6.3%
91 2.0% 217 3.7% 308 2.9%
45 1.0%
82 1.4% 127 1.2%
5.2 Characteristics of adults under 50 years of age
Among adults under 50 years old, men were more physically active and women
had a higher prevalence of depression (Table 14). Ethnicity was similar among men and
women. In general, the characteristics of men and women under 50 years of age were
similar to that of all adults over 18 years of age, with the exception that a lower
percentage of men reported cancer than women among younger adults (1.7% men versus
5.2% women) and higher percentage of women were under the age of thirty. Although
the prevalence of mild depression (17.3% women versus 17.2% men) was similar by
gender, women had higher prevalence of dysthymia depression (8.8% women versus
6.7% men), moderate depression (4.3% women versus 2.4% men), and major depression
(1.5% women versus 1.2% men) than men. Women had a higher prevalence of cancer
65
and arthritis than men. The proportion of men using statin medications was higher than
the proportion of women using statin medications. This latter observation may be related
to the higher proportion of men with CVD. Slightly more women were classified as obese
(39.9% women versus 38.9% men). A significantly higher proportion of men reported
moderately intense physical activity than women in a typical month (68.6% men versus
42.6% women).
66
Table 14. Descriptive statistics of moderately intense activity and other selected
characteristics among adults under 50: NHANES 1999-2012
Characteristics
Age (years)
under 30
30 to 50
male
(n=1555)
female
(n=2572)
433 27.8% 932 36.2% 1365 33.1%
1122 72.2% 1640 63.8% 2762 66.9%
BMI (kg/(m2))
Not obese (BMI < 30)
950 61.1% 1547 60.1%
Obese (BMI ≥ 30)
605 38.9% 1025 39.9%
Ethnicity
Non-Hispanic White
889 57.2% 1407 54.7%
African American
257 16.5% 506 19.7%
Other
409 26.3% 659 25.6%
Medical conditions (same adult may have multiple diseases)
Arthritis
245 15.8% 420 16.3%
Cancer
27 1.7% 133 5.2%
Cardiovascular diseases
75 4.8%
87 3.4%
No CVD, No Arthritis, No
1247 80.2% 2034 79.1%
Cancer
Moderate Intensity Activity
(MIA)
no MIA
MIA
Total
(n=4127)
2497 60.5%
1630 39.5%
2296 55.6%
763 18.5%
1068 25.9%
665 16.1%
160 3.9%
162 3.9%
3281 79.5%
488 31.4% 812 19.7% 1300 31.5%
1067 68.6% 1760 42.6% 2827 68.5%
Continued
67
Table 14: continued
Statins
Simvastatin
Lovastatin
Cerivastatin
Atorvastatin
Pitavastatin
Fluvastatin
Pravastatin
Rosuvastatin
Depression
0 to 4 None
5 to 9 Mild
10 to 14 Dysthymia
15 to 19 Moderate
20+ Major
76
16
n/a
61
n/a
2
16
13
4.9%
1.0%
n/a
3.9%
n/a
0.1%
1.0%
0.8%
63
7
n/a
26
n/a
0
23
15
2.4%
0.3%
n/a
1.0%
n/a
0.0%
0.9%
0.6%
139
23
n/a
87
n/a
2
39
28
3.4%
0.6%
n/a
2.1%
n/a
0.0%
0.9%
0.7%
1128 72.5% 1753 68.2% 2881 69.8%
268 17.2% 444 17.3% 712 17.3%
104 6.7% 226 8.8% 330 8.0%
37 2.4% 110 4.3% 147 3.6%
18 1.2%
39 1.5%
57 1.4%
5.3 Characteristics of adults over 50 years of age
Among adults over the age of 50 years old, more men reported “moderate
intensity physical activity” than women while more women had depression than men
(Table 15). Adults over the age of 50 years old had similar patterns of descriptive
characteristics as the entire group of adults over the age of 18 years old. Various severity
level of depression was significantly more common in women. The prevalence of mild,
dysthymia, moderate, and major depression in women (18.2%, 6.4%, 3.3%, and 1.3%,
respectively) were consistently and significantly higher than the corresponding
prevalence of depression in men (11.9%, 4.1%, 1.8%, and 0.9%, respectively). More men
exercised at moderate intensity in a typical month than women (60.3% men versus 53%
women). More women were classified as obese (BMI  30) than men (44.6% women
68
versus 38.4% men), even though the average age and ethnicity distribution were similar
between men and women. More men had cancer (20.2% men versus 17% women), while
more women reported arthritis (56.7% women versus 43.6% men). Higher prevalence of
cardiovascular disease in men (27.9% men versus 17.5% women) was consistent with the
higher usage of cholesterol lowering statin medications in men. Lipophilic statins were
overwhelmingly more common than hydrophilic statins in both men and women. The top
3 most common statins included simvastatin (22.1% men versus 16.8% women),
atorvastatin (12.9% men versus 11.4% women), and lovastatin (4.7% men versus 3.6%
women). Pitavastatin and Fluvastatin were rarely used in men and women.
For the purpose of gender specific statistical analyses of various age strata, the
lipophilic statin category included Simvastatin, Lovastatin, Atorvastatin, whereas the
hydrophilic statin category included Pravastatin, and Rosuvastatin. Cerivastatin was
listed in NHANES database even though it was discontinued and was not in use.
Pitavastatin and Fluvastatin were the least commonly used statin medications.
69
Table 15. Descriptive statistics of moderately intense activity and other selected
characteristics among adults at least 50 years of age: NHANES 1999-2012
Characteristics
male
(n=3062)
female
(n=3271)
Age (years), mean
66.4 years
BMI (kg/(m2))
Not obese (BMI < 30)
1886 61.6% 1813 55.4% 3699 58.4%
Obese (BMI ≥ 30)
65.9 years
Total
(n=6333)
66.2 years
1176 38.4% 1458 44.6% 2634 41.6%
Ethnicity
Non-Hispanic White
1758 57.4% 1745 53.3% 3503 55.3%
African American
608 19.9%
675 20.6% 1283 20.3%
Other
696 22.7%
851 26.0% 1547 24.4%
Medical conditions (same adult may have multiple diseases)
Arthritis
Cancer
Cardiovascular diseases
No CVD, No Arthritis, No
Cancer
Moderate Intensity Activity
(MIA)
no MIA
MIA
1335 43.6% 1856 56.7% 3191 50.4%
619 20.2%
855 27.9%
556 17.0% 1175 18.6%
574 17.5% 1429 22.6%
1075 35.1% 1069 32.7% 2144 33.9%
1216 39.7% 1538 47.0% 2754 43.5%
1846 60.3% 1733 53.0% 3579 56.5%
Continued
70
Table 15: continued
Statins
Simvastatin
677 22.1%
550 16.8% 1227 19.4%
Lovastatin
143
118
Cerivastatin
n/a
Atorvastatin
Pitavastatin
4.7%
n/a
395 12.9%
1 0.0%
3.6%
n/a
n/a
373 11.4%
0.1%
261
4.1%
n/a
n/a
768 12.1%
0.0%
0.1%
3
11
Fluvastatin
7
0.2%
2
4
Pravastatin
110
3.6%
106
3.2%
216
3.4%
Rosuvastatin
Depression
108
3.5%
110
3.4%
218
3.4%
0 to 4 None
0.2%
2493 81.4% 2319 70.9% 4812 76.0%
5 to 9 Mild
363 11.9%
594 18.2%
957 15.1%
10 to 14 Dysthymia
125
4.1%
208
6.4%
333
5.3%
15 to 19 Moderate
54
1.8%
107
3.3%
161
2.5%
20+ Major
27
0.9%
43
1.3%
70
1.1%
5.4 Moderately intense physical activity and depression
Moderately intense physical activity was inversely and significantly associated
with depression (PHQ9  10) in men and women, as shown by the gender-stratified
binomial logistic regression models (Table 16). All estimates were adjusted for age, BMI,
corticosteroids, statins, total cholesterol, HDL, arthritis, cancer, CVD. Depression (PHQ9
 10)
was inversely associated with “moderately intensity activity” in women under 50
years of age (OR=0.62 with 95% CI = (0.49, 0.78)) as well as in all women over 18 years
of age (OR=0.58 with 95% CI = (0.49, 0.68)). The odds ratio of depression (PHQ9  10)
associated with “moderately intensity activity” was similar in men under 50 years of age
71
(OR=0.54 with 95% CI = 0.38, 0.76), and in all men over 18 years of age (OR=0.47 with
95% CI = 0.37, 0.58). Unadjusted and age-adjusted models yielded similar results:
“moderate intensity physical activity” was inversely and significantly associated with
depression (PHQ9  10) in men and women.
72
Table 16. Odds ratios of depression (PHQ9  10) associated with moderately intense
activity in age-stratified women and men: NHANES 1999-2012
Depression
(PHQ9  10)
Women
OR
OR 95% CI
Aged < 50, n=2572
OR
OR 95% CI
All women, n=5843
moderately
intense
activity
0.62
0.58
Men
Aged < 50, n=1555
moderately
intense
activity
0.54
(0.49,
(0.38,
0.78)
0.76)
(0.49,
0.68)
All men, n=4617
0.47
(0.37,
0.58)
* Adjusted for age, BMI, and medical condition (CVD, cancer, arthritis), corticosteroid,
statins, total cholesterol, low HDL status
In gender-stratified multinomial logistic regression models, the trend of the odds
ratios of severity levels of depression (e.g. from mild depression to major depression)
associated with moderately intense physical activity consistently and significantly
declined in men and women with adjustment for age, body mass index, medical
conditions (arthritis, cancer, CVD), corticosteroids, statins, total cholesterol, and HDL
cholesterol. For example, the odds ratio of major depression associated with moderately
intense physical activity was lower than the odds ratio of mild depression associated with
moderately intense physical activity. In men, the moderate depression and major
depression categories were merged due to the low number of men with major depression.
73
There were sufficient numbers of women in all four severity levels of depression for
analysis. Significant inverse trends in the odds ratios by severity levels of depression
were evident in all multinomial logistic analyses of adults including women under the age
of 50, men under the age of 50, women over the age of 18, and men over the age of 18.
Non-parametric trend tests were statistically significant.
Table 17. Odds ratios of depression severity (mild, dysthymia, moderate, major)
associated with moderately intense activity: NHANES 1999-2012
Depression
Severity
Adjusted
Odds
Ratios*
(OR)
OR 95% CI
Aged < 50, n=2572
Women
None
Mild
Dysthymia
Moderate
Major
Men
None
mild
dysthymia
ModerateMajor
Combined
1
Reference
0.76
(0.60 ,
0.94)
0.67
(0.49 ,
0.89)
0.48
(0.32,
0.72)
0.43
(0.22,
0.84)
Aged < 50, n= 1555
1
0.86
0.58
Reference
(0.64,
(0.38,
1.15)
0.88)
0.42
(0.24,
0.75)
Adjusted
Odds
Ratios*
(OR)
OR 95% CI
All women >=18 years old,
n=5843
1
Reference
0.80
(0.69 ,
0.92)
0.63
(0.51 ,
0.77)
0.51
(0.38 ,
0.68)
0.30
(0.18,
0.48)
All men>=18 years old,
n=4617
1
Reference
0.71
(0.59,
0.84)
0.44
(0.34,
0.59)
0.43
(0.30,
0.62)
Trend test p<0.01
* Adjusted for age, BMI, medical conditions (CVD, cancer, arthritis), medication use
(corticosteroids, statins), total cholesterol, and HDL.
74
The odds ratios of depression associated with moderately intense physical activity
decreased with each severity level of depression (mild depression > dysthymia depression
> moderate depression > major depression). Trends in the odds ratios of depression
severity associated with moderately intense activity were similar among women under 50
years old, all women over 18 years old, men under 50 years old, and all men over 18
years old (Table 17). Covariate adjustments included age, BMI, medical conditions
(CVD, cancer, and arthritis), medication use (corticosteroids, statins) total cholesterol,
and HDL cholesterol. The 95% confidence intervals of OR estimates in women and men
reflect statistical significance, with the exception of mild depression among men under 50
years old. In women under 50 years of age, the odds ratios of mild, dysthymia, moderate,
and major depression associated with “moderately intense activity” were 0.76, 0.67,0.47,
0.43, respectively, whereas in all women over 18 years of age, the odds ratios of mild,
dysthymia, moderate, and major depression associated with “moderately intense activity”
were 0.8, 0.63, 0.51, 0.3, respectively (Figure 5). The odds ratios of mild, dysthymia,
merged-moderate-major depression associated with “moderately intense activity” were
0.86, 0.58, and 0.42 respectively in men under 50 years old (Figure 6). In men, the odds
ratios for progressively worse severity levels of depression (associated with moderately
intense physical activity) were lower than the odds ratio for mild depression. These trends
significantly and consistently decline in women and men, regardless of age categories.
Results of the non-parametric trend tests for theses strata were significant (p<0.01),
supporting the beneficial association between moderately intense physical activity and
depression severity level.
75
Figure 5. Odds ratios of depression severity associated with moderately intense activity in
women: NHANES 1999-2012
Age-stratified Women: Odds ratios of depression associated
with moderate intensity activity
0.90
Odds Ratios of Depression
0.80
0.70
0.60
0.50
0.40
0.30
0.20
0.10
0.00
Mild
Dysthymia
Moderate
Women Aged < 50
Major
Women >=18 years old
* Adjusted for age, BMI, medical conditions (CVD, cancer, arthritis), use of medications
(corticosteroids, statins), total cholesterol and HDL cholesterol.
76
Figure 6. Odds ratios of depression severity associated with moderately intense activity in
men: NHANES 1999-2012
Age-stratified men: Odds ratios of depression
associated with moderate intensity activity
1.00
Odds Ratios of Depression
0.90
0.80
0.70
0.60
0.50
0.40
0.30
0.20
0.10
0.00
mild
dysthymia
Men Aged < 50
Moderate-Major
Combined
Men >=18 years old
* Adjusted for age, BMI, medical conditions (CVD, cancer, and arthritis), use of
medications (corticosteroids, statins), total cholesterol and HDL cholesterol.
77
Chapter 6 CVD, physical activity, depression
6.1 Moderately intense physical activity and depression in CVD strata
Among adults diagnosed with cardiovascular diseases (CVD), moderately intense
physical activity was found to be inversely associated with depression. Cardiovascular
diseases included congestive heart failure, coronary heart disease, angina pectoris,
myocardial infarction, ischemic stroke, and hemorrhagic stroke. The results were similar
in crude and adjusted multinomial logistic regression models controlling for medication
use (corticosteroids, statins), total cholesterol, HDL, age, BMI, and other medical
conditions.
The trend of the severity level of depression associated with moderately intense
physical activity declined significantly among adults diagnosed with CVD as well as
among adults without CVD. Analyses were completed for gender-stratified groups: (i)
adults with CVD, (ii) adults without CVD, and (iii) adults without CVD or arthritis
(Table 18). In women with CVD, the odds ratios of mild, dysthymia, moderate, and
major depression associated with moderately intense physical activity were 1.0, 0.82,
0.37, and 0.21, respectively. In men with CVD, the odds ratios of mild, dysthymia, and
combined moderate-major-depression associated with moderately intense physical
activity were 0.49, 0.29, and 0.20, respectively. For adults with CVD, all estimations of
odds ratios were significant except for women with mild depression or dysthymia. These
78
trends were similar in the adults without CVD, as well as the adults without CVD or
arthritis. For adults with CVD, all the confidence intervals were significant except for
women with mild depression or dysthymia.
In women without CVD or arthritis, the odds ratios of mild, dysthymia, and
combined moderate-major-depression associated with moderately intense physical
activity were 0.74, 0.63, 0.62, and 0.29, respectively. Similarly in men without CVD or
arthritis, the odds ratios of mild, dysthymia, and combined moderate-major-depression
associated with “moderate intensity activity” were 0.83, 0.53, and 0.54, respectively. For
adults without CVD and without arthritis, all the confidence intervals were significant
except for men with mild depression. As the severity level of depression worsened (e.g.
from mild depression to major depression), the odds ratios of depression associated with
“moderate intensity activity” decreased. In particular, the odds ratios of mild depression
associated with “moderate intensity activity” were the highest; the odds ratios of
moderate and major depression associated with “moderate intensity activity” were the
lowest.
79
Table 18. Odds ratios of depression severity associated with moderately intense activity
in adults stratified by cardiovascular disease: NHANES 1999-2012
Statinsadjusted
OR
OR 95% CI
CVD,
n=661
Women
None
1
Ref
Mild
1
(0.66,
Dysthymia 0.82 (0.44,
Moderate 0.37 (0.18,
Major
0.21 (0.07,
Men
None
mild
1.50)
1.51)
0.75)
0.60)
CVD,
n=930
1
Ref
0.49 (0.33, 0.72)
No CVD,
n=3687
1
Ref
0.78 (0.63, 0.95)
OR
95%
OR
CI
No CVD
& No Arthritis,
n=3363
1
Ref
0.74
(0.61, 0.91)
0.63
(0.46, 0.84)
0.62
(0.40, 0.96)
0.29
(0.14, 0.59)
No CVD
& No Arthritis,
n=2561
1
Ref
0.83
(0.64, 1.07)
OR
1
0.77
0.61
0.55
0.33
OR 95% CI
No CVD,
n=5182
Ref
(0.66,
(0.49,
(0.39,
(0.19,
0.90)
0.76)
0.75)
0.57)
Dysthymia 0.29 (0.15,
0.56)
0.49
(0.36,
0.67)
0.53
(0.35,
0.77)
ModerateMajor
Combined
0.43)
0.58
(0.38,
0.89)
0.54
(0.32,
0.92)
0.2
(0.09,
Trend test p<0.01
* adjusted for total cholesterol, HDL, age, BMI, cancer, medication use (statins,
corticosteroids); stratified by CVD status and arthritis status
80
The inverse association between “moderate intensity activity” and depression
severity were particularly beneficial among men with CVD. Men with CVD had lower
odds ratios of comparable severity levels of depression associated with “moderate
intensity activity” than women with CVD. Additionally, men with CVD had lower odds
ratio of depression associated with “moderate intensity activity” than men without CVD.
The CVD category included congestive heart failure, coronary heart disease, angina
pectoris, myocardial infarction, and stroke. The men with CVD had lower odds ratio of
mild depression associated with “moderate intensity activity” than women (OR=0.49 men
versus OR=1.0 women). Men with diagnosed CVD also had lower odds ratios of
dysthymia associated with “moderate intensity activity” than women (OR=0.29 for men
versus OR=0.82 for women). A similar pattern was noted in comparing men with CVD to
men without CVD. The odds ratio of mild depression associated with “moderate intensity
activity” in men with CVD (OR=0.49) was lower than the odds ratio of mild depression
associated with “moderate intensity activity” in men without CVD (OR=0.78). The odds
ratio of dysthymia associated with “moderate intensity activity” in men with CVD
(OR=0.29) was also lower than the odds ratio of dysthymia associated with “moderate
intensity activity” among men without CVD (OR=0.49). The odds ratio of combined
moderate-major depression associated with “moderate intensity activity” in men with
CVD (OR=0.20) was similarly lower than the odds ratio of combined moderate-major
depression associated with “moderate intensity activity” in men without CVD
(OR=0.58). The odds ratios of depression severity associated with “moderate intensity
81
activity” exhibited declining patterns in women (Figure 7) and men (Figure 8) with and
without cardiovascular disease.
Figure 7. Adjusted Odds ratios of depression severity (mild, dysthymia, moderate, major
depression) associated with moderately intense activity in women with and without CVD:
NHANES 1999-2012
Women: Disease-stratified Odds ratios (OR) of
depression associated with moderate intensity activity,
NHANES 1999 to 2012
Odds Ratios of Depression
1.2
1
0.8
0.6
0.4
0.2
0
Mild
Dysthymia
Moderate
Major
Women with CVD
Women: No CVD
Women: No CVD & No Arthritis
* Adjusted for age, body mass index, cancer, medication use (statins, corticosteroids),
total cholesterol, HDL cholesterol.
82
Figure 8. Adjusted Odds ratios of depression severity (mild, dysthymia, moderate, major
depression) associated with moderately intense activity in men with and without CVD:
NHANES 1999-2012
Odds Ratios of Depression
0.9
Men: Disease-stratified Odds ratios (OR) of depression
associated with moderate intensity activity
0.8
0.7
men with CVD
0.6
Men: No CVD
0.5
Men: No CVD & No Arthritis
0.4
0.3
0.2
0.1
0
* Adjusted for age, body mass index, cancer, medication use (statins, corticosteroids),
total cholesterol, HDL cholesterol.
83
6.2 Results of unadjusted analyses of statins
Depression, physical activity, and cholesterol level were compared among
different groups of statin users and non-users (i.e. no statin treatment, hydrophilic statin,
and lipophilic statin treatment) in unadjusted gender- and age-stratified analyses. Men
and women were stratified at the age of 50 and analyzed separately. There was not a
separate category of adults using both lipophilic statins and hydrophilic statins because of
the very low number of adults taking both types of statins. For example, only three
women were taking both lipophilic and hydrophilic statin medications. The statin
categories included non-users, lipophilic statin users, and hydrophilic statin users.
Women taking statin had higher prevalence of depression (PHQ9  10) than
women not taking statins. The proportions of adults reporting moderately intense physical
activity were similar across various categories of statin users and non-users. The group of
adults over 50 years old had lower prevalence odds of depression associated with
“moderate intensity activity” than the group of adults under 50 years old. In women, the
prevalence of depression (PHQ9  10) in statins-users were significantly higher than
women not using statins, in both age categories. In women under 50 years of age, the
prevalence estimates of depression in non-statin users, users of a hydrophilic statin and
users of a lipophilic statin were 14.3%, 29%, 24%, respectively. In women at and over 50
years of age, these prevalence estimates of depression were 10.7%, 13%, 11.4%,
respectively (Table 19). For women under 50 years old, means of total cholesterol and
LDL cholesterol and frequencies of physical activity were not significantly different
between statin-users and non-users; however, HDL cholesterol was significantly lower
84
among female statin-users. For women at least 50 years of age, women using a statin had
lower total cholesterol, lower LDL cholesterol, and lower HDL cholesterol than those
women not using statins, whereas the prevalence estimates of moderately intense physical
activity were similar across groups using lipophilic statins, hydrophilic statins or not
using statins.
The group of men over 50 years of age exhibited significant differences in
characteristics across the various statin categories, whereas the group of men under 50
years old did not demonstrate significant differences in characteristics across the various
statin categories. The prevalence of exercise at moderate intensity was similar across all
categories of statin users and non-users in the group of men under 50 years old and the
group of men at least 50 years old. In men over 50 years old, men who were not taking
statin medications had significantly higher levels of total cholesterol, HDL cholesterol
and LDL cholesterol, and a higher prevalence of depression. In men over 50 years old,
the prevalence of depression in non-users of statins, hydrophilic statins users and
lipophilic statin users were 7%, 4%, and 5%, respectively. Among men under 50 years
old, levels of total cholesterol, HDL cholesterol, and LDL cholesterol were similar and
not significantly different across all statin categories (Table 20). In men under 50 years of
age, the prevalence of depression did not differ significantly across different categories of
statin users and non-users.
85
Table 19. Characteristics by statin categories in women: NHANES 1999-2012
Women aged  50
Women aged < 50
Hydrophilic
No
statin
statin
only
Total
Cholesterol
(mg/dL)
HDL
(mg/dL)
LDL
(mg/dL)
Lipophilic
statin anova
only p
Hydrophilic
No
statin
statin
only
Lipophilic
statin anova
only p
193.3
193.3
200
0.21
213.4
190.8
186.4
0.01
53.5
50.4
48.9
0.04
58.3
56.1
56.9
0.04
110.7
127
111
0.1
118
102
101
0.11
68%
66%
57%
0.53
54%
48%
51%
0.06
%depressed
PHQ9  10
14% 29.0% 24.0% <0.01 10.7%
* Physical activity at moderate intensity in a typical month
13.0%
11.4%
<
0.01
% exercise*
86
Table 20. Characteristics by statin categories in men: NHANES 1999-2012
Men aged < 50
Men aged  50
Hydrophilic
No
statin
statin
only
Lipophilic
statin anova
only p
No
statin
Hydrophilic
statin
only
194.7
195.1
189.9
0.36
185.8
169.4
168.4
0.01
43.8
40.3
43.5
0.44
48.4
46.1
48.1
0.02
117.8
120.9
107.5
0.07
108
96.7
91.2
0.01
68.0%
84.0%
67.0%
0.17
60%
57%
61%
0.73
%depressed
PHQ9 10
10.4%
9.0% 10.5%
0.9
7%
* Physical activity at moderate intensity in a typical month
4%
5%
0.01
Total
Cholesterol
(mg/dL)
HDL
(mg/dL)
LDL
(mg/dL)
%exercise*
Lipophilic
statin anova
only p
More men were taking statins than women (35.24% men versus 23.91% women)
and lipophilic statins were more popular than hydrophilic statins among both women and
men (Table 21). The category of lipophilic statins included Simvastatin, Lovastatin,
Cerivastatin, Atorvastatin, Pitavastatin). The category of hydrophilic statins (Fluvastatin,
Pravastatin, Rosuvastatin). The most commonly taken lipophilic statin was Simvastatin,
and the second most popular lipophilic statin was Atorvastatin. Over five times more
adults took Simvastatin than Lovastatin. The unadjusted analysis included only adults
with non-missing and valid data in the fields of depression, physical activity,
medications, and demographics. In men, the top 3 most commonly taken statins were
87
Simvastatin (16.3%), Atorvastatin (9.95%), and Lovastatin (3.45%). In women, the most
common statins were Simvastatin (10.49%), Atorvastatin (6.83%), Pravastatin (2.21%),
and Lovastatin (2.14%), and Rosuvastatin (2.14%). Although NHANES listed
Cerivastatin in the medication database, Cerivastatin was discontinued and withdrawn
from the world market due to its adverse side effect of rhabdomyolysis and kidney
failure. No adults in this dataset used Cerivastatin. Very few adults reported using
Pitavastatin and Fluvastatin. In men, lipophilic statins were more commonly used than
hydrophilic statin (29.6% lipophilic versus 5.5% hydrophilic statin among men). In
women, lipophilic statins were more commonly used than hydrophilic statin (25.6%
lipophilic versus 5.8% hydrophilic statin among women). The prevalence of lipophilic
statin usage exceeded the prevalence of hydrophilic statin usage in both men and women.
The prevalence of statin usage in men was higher than the prevalence of statin usage in
women.
88
Table 21. Distribution of various statin medication usage among men and women with
valid depression, demographics, and physical activity data: NHANES1999-2012
No Statin
Men (N=4617)
Women (N=5843)
2992 64.80%
4446 76.09%
Lipophilic
statins:
Simvastatin
Lovastatin
Cerivastatin*
Atorvastatin
Pitavastatin
753 16.13%
159 3.44%
Withdrawn discontinued
456 9.88%
1 0.02%
613 10.49%
125 2.14%
399
2
6.83%
0.03%
Hydrophilic statins:
Fluvastatin
Pravastatin
9
126
4
129
0.07%
2.21%
0.19%
2.73%
Rosuvastatin
121 2.62%
125 2.14%
* Cerivastatin was listed in NHANES but it has been withdrawn from the market.
89
6.3 Results of adjusted analyses of statins
In binomial logistic regression analyses that adjusted for statins, moderately
intense physical activity was significantly and inversely associated with depression
(PHQ9  10) in both men and women. The beneficial inverse associations between
moderately intense physical activity and depression (PHQ9  10) were consistently found
in all four adult age groups, while controlling for use of lipophilic statin and hydrophilic
statins: in women without CVD (OR=0.59 with 95% CI= 0.50, 0.71), in women with
CVD (OR=0.52 with 95% CI= 0.33, 0.82), in men without CVD (OR=0.56 with 95%
CI= 0.43, 0.72), and in men with CVD (OR=0.29 with 95% CI= 0.18, 0.48). Other
biomarkers, demographic parameters, and medical conditions were not consistently
related to depression in these four CVD-stratified age groups. Medical conditions such as
arthritis and cancer were not consistently associated with worsened odds of depression
associated with “moderate intensity activity”. Body Mass Index and HDL cholesterol
were not significantly related to depression in women with CVD and men with CVD.
Moderately intense physical activity was significantly, consistently, and inversely
associated with depression, while controlling for age, BMI, waist circumference, use of
lipophilic or hydrophilic statins, total cholesterol, HDL cholesterol, corticosteroids,
arthritis, and cancer.
In women without CVD, the category of lipophilic statin use was associated with
an increased odds ratio of depression (PHQ9  10) (OR= 1.33 with 95% CI=1.02, 1.73)
with adjustment for age, body mass index, waist circumference, HDL, total cholesterol,
medical conditions and moderately intense physical activity. In women with CVD, none
90
of the medication were significantly associated with depression (PHQ9  10) in binomial
logistic regression models (Table 22). Total cholesterol exceeding 200mg/dL was
associated with higher odds of depression in women with CVD (OR=1.69) and women
without CVD (OR=1.23).
Table 22. Odds ratios of depression (PHQ9  10) associated with use of statins in women
with and without CVD diagnoses: NHANES 1999-2012*
Women,
stratified by
CVD
Number
Lipophilic
Statin
Hydrophilic
Statin
Corticosteroid
Total
Cholesterol
( 200mg/dL)
Poor HDL
(<50 mg/dL)
Moderate
intensity
activity
Odds
Ratio (OR)
of
OR 95% CI,
Depression women free of
PHQ9  10
CVD
# non-CVD women, n=5182
Odds Ratio
(OR) of
OR 95% CI,
Depression
women w/
PHQ9  10
CVD
# women with CVD, n=661
1.33
(1.02, 1.73)
1.01
(0.61, 1.66)
1.37
1.53
(0.83, 2.12)
(0.94, 2.49)
1.6
2.17
(0.80, 3.21)
(0.79, 5.97)
1.23
(1.02, 1.48)
1.69
(1.08, 2.64)
1.45
(1.21, 1.74)
1.27
(0.81, 1.97)
0.59
(0.50, 0.71)
0.52
(0.33, 0.82)
* Estimates are adjusted for age, waist circumference, BMI, HDL cholesterol, total
cholesterol, medical conditions (arthritis, cancer), corticosteroid use and moderately
intense physical activity
91
In men without CVD and in men with CVD, lipophilic statin was not associated
with depression (PHQ9  10). In men with CVD, hydrophilic statin was not significantly
associated with depression but was associated with lower odds of depression (OR=0.34
with 95%CI = (0.12, 0.95)), as shown by the results of binomial logistic regression
(Table 23). Moderate intensity physical exercise was consistently, significantly and
beneficially associated with lowered prevalence odds of depression (PHQ9  10) in men
without CVD (OR=0.56) and in men with CVD (OR=0.29). In men, total cholesterol
level ( 200mg/dL) and HDL (<40mg/dL) were not significantly related to depression.
Unlike women, total cholesterol exceeding 200mg/dL was not associated with higher
odds of depression in men with CVD and in men without CVD.
92
Table 23. Odds ratios of depression (PHQ9  10) associated with use of statins in men
with and without CVD diagnoses: NHANES 1999-2012*
Men,
stratified by
CVD
N
Lipophilic
Statin
Hydrophilic
Statin
Corticosteroid
Odds
Odds Ratio
Ratio
(OR) of
OR 95% CI,
(OR) of
depression men free of depression
OR 95% CI,
PHQ  10
CVD
PHQ  10
men w/ CVD
# non-CVD men, n=3687 # men with CVD, n=930
0.78
(0.54, 1.12)
0.72
(0.41, 1.24)
0.34
1.24
(0.12, 0.95)
(0.55, 2.78)
0.78
0.58
(0.33, 1.82)
(0.13, 2.69)
Total
Cholesterol
( 200mg/dL)
1.07
(0.82, 1.39)
1.31
(0.75, 2.28)
Poor HDL
(<40 mg/dL)
1.16
(0.88, 1.53)
1.33
(0.82, 2.16)
Moderate
intensity
activity
0.56
(0.43, 0.72)
0.29
(0.18, 0.48)
* Estimates are adjusted for age, waist circumference BMI, HDL cholesterol, total
cholesterol, medical conditions (arthritis, cancer), corticosteroid use and moderately
intense physical activity.
93
6.4 Duration of statins
In women, longer duration of lipophilic statins treatment was associated with
higher odds ratios of depression (in comparing women who exercised at moderate
intensity with women who did not), whereas longer duration of hydrophilic statin
treatment did not alter the anti-depressive associations with “moderate intensity activity”.
The odds ratios of depression (PHQ9  10) associated with moderately intense physical
activity were plotted over the duration of statin treatment (Figure 9) for these three
groups of women: (i) the subgroup of women free of CVD who were taking lipophilic
statin; (ii) subgroup of women diagnosed with CVD taking lipophilic statin; and (iii)
subgroup of women taking hydrophilic statin adjusting for CVD. In women with CVD
who received lipophilic statin treatment, the odds ratios of depression associated with
moderately intense physical activity increased with the duration of treatment at the fastest
pace. In women without diagnosed CVD who received lipophilic statin treatment, the
odds ratios of depression associated with moderately intense physical activity increased
at a slower pace with duration of treatment. In contrast, among women taking hydrophilic
statin, the odds ratios of depression associated with moderately intense physical activity
fluctuated instead of worsening over time.
Lipophilicity of statins and the presence of cardiovascular conditions appeared to
play a role in the trends in the odds ratio of depression (PHQ9  10) associated with
“moderate intensity activity” over the duration of statin treatment. In women with CVD,
using a lipophilic statin for over 550 days elevated the odds ratios of depression (PHQ9 
10) associated with “moderate intensity activity” from 0.6 to 0.91 (Figure 10). In women
94
without CVD, the odds ratios of depression associated with “moderate intensity activity”
rose from 0.6 to 0.89 among women who were using a lipophilic statin for over 800 days
(Figure 11). In women taking a hydrophilic statin, odds ratios did not exhibit a trend with
duration of use but rather fluctuated about OR=0.60 even after adjusting for the presence
of cardiovascular disease (Figure 12). In women taking a hydrophilic statin, the odds
ratios of depression associated with moderately intense physical activity remained
relatively constant (between 0.68 and 0.57) as the duration of hydrophilic statin usage
increased to two years and beyond, while adjusting for cardiovascular disease.
Among men without any CVD who were taking a lipophilic statin, the odds ratios
of depression associated with “moderate intensity activity” increased from 0.57 to 0.86 as
the duration of statin treatment reached 750 days (Figure 13). There were statistically
insufficient number of men taking hydrophilic statin who also had non-missing valid
depression data and physical activity data. Therefore, the men taking a hydrophilic statin
were combined with the men taking a lipophilic statin in the subsequent analysis of
hydrophilic statin, while adjusting for CVD. Incorporating hydrophilic statin into the
CVD-adjusted analysis of men taking any stain resulted in the stagnating odds ratio of
depression associated with “moderate intensity activity” over the duration of any statin
treatment. Among men taking either hydrophilic or lipophilic statin, the trend of the odds
ratio of depression associated with “moderate intensity activity” fluctuated without
obvious trend, while adjusting for CVD (Figure 14).
The confidence bands of these odds ratios were wide in these figures due to the
insufficient number of adults taking a statin at various time points. The confidence
95
intervals of the odds ratios of depression associated with “moderate intensity activity” at
various time points of statin usage were not narrow. The limited number of adults taking
a statin who had non-missing depression and physical activity data were not large enough
to create narrow confidence intervals in these figures.
Physical activity did not appear to contribute to the observed differences in the odds
ratios of depression associated with “moderate intensity activity” with increasing duration
of lipophilic versus hydrophilic statin use. Among both women and men stratified by CVD
and lipophilicity of statins, the observed proportions of adults who exercised at moderate
intensity were similar across the duration of statin treatment. Among women with CVD
and taking a lipophilic statin, the proportion exercising at moderate intensity for at least
ten minutes per month (~37%) remained roughly the same over the duration of statin
treatment. Among women without CVD taking a lipophilic statin, the proportion exercising
at moderate intensity for at least ten minutes per month (~57%) also stayed at the same
level over the duration of statin treatment. Among women taking a hydrophilic statin and
adjusted for CVD, the proportion of women exercising at moderate intensity for at least
ten minutes per month was found to stay at similar level over the duration of statin
treatment.
96
Figure 9. Comparing the trends of odds ratios of depression associated with “moderate
intensity activity” over duration of statin treatment, among women in different strata of
CVD using a lipophilic/hydrophilic statin: NHANES 1999-2012*
*adjusting for age, body mass index, ethnicity, total cholesterol, HDL, arthritis,
cancer, corticosteroid: NHANES 1999-2012
97
Figure 10. Lipophilic statin treatment in women with CVD: NHANES 1999-2012
Odds ratios of depression (associated with moderately intense physical activity) were
plotted over the duration of lipophilic statin treatment among CVD stratified women.
Figure 11. Lipophilic statin treatment in women free of CVD: NHANES 1999-2012
98
Figure 12. Hydrophilic statin in CVD-adjusted women: NHANES 1999-2012
In women taking a hydrophilic statin, the odds ratios of depression (associated with
moderately intense physical activity) were plotted over the duration of hydrophilic statin
while adjusting for CVD.
99
Figure 13. Lipophilic statin treatment in men free of CVD: NHANES 1999-2012
*adjusting for age, BMI, ethnicity, Total Cholesterol, HDL, arthritis, cancer, and
corticosteroid: NHANES 1999-2012
Figure 14. Any statin treatment in men adjusting for CVD: NHANES 1999-2012
*adjusting for age, BMI, ethnicity, Total Cholesterol, HDL, arthritis, cancer, CVD, and
corticosteroid: NHANES 1999-2012
100
6.5 Muscle strengthening activity and depression in CVD strata
Among adults with CVD, the odds ratios of depression (PHQ9  10) associated
with “muscle strengthening activity” were lower in adults who performed muscle
strengthening activity, even after adjustments for aerobic activities. The odds ratios of
more severe depression associated with muscle strengthening activity were lower than the
odds ratios of mild depression associated with muscle strengthening activity. Among
women with CVD, the odds ratios of mild and dichotomized depression associated with
muscle strengthening activity were 0.4, 0.33, respectively, after adjusting for aerobic
activity, age and body mass index. Among men with CVD, the odds ratios of mild and
dichotomized depression associated with muscle strengthening activity were 0.53, 0.42,
respectively, while adjusting for age, body mass index, aerobic activity. While these
estimations of odds ratios supported the inverse association, the small sample sizes (215
women diagnosed with CVD and 157 men diagnosed with CVD) and low sub cell sizes
contributed to the wide confidence intervals. Due to the limited availability of muscle
strengthening data and the fewer number of adults engaging in muscle strengthening
activity, all cardiovascular diseases were merged to include “congestive heart failure,
coronary heart disease, angina pectoris, myocardial infarction, and stroke.” These
medical conditions were enumerated in the list of NHANES medical condition file.
Although the estimated “aerobic activity-adjusted” odds ratios supported the inverse
association between depression and anaerobic muscle strengthening activity among
adults diagnosed with CVD, the corresponding confidence intervals were wide and did
not reach statistical significance.
101
Table 24. Odds ratios of depression associated with muscle strengthening activity in
adults diagnosed with CVD: NHANES 1999 to 2006
OR
OR 95% CI
Women with CVD*
Women
None
Mild
PHQ  10
1
Ref
0.53
(0.15, 2.0)
0.33
(0.07, 1.5)
Trend test p<0.01
Men with CVD*
Men
None
mild
PHQ  10
1
Ref
0.48
(0.16, 1.4)
0.38
(0.10, 1.3)
Trend test p<0.01
OR
OR 95% CI
Women with CVD**
(n=199)
1
Ref
0.4
(0.10, 1.5)
0.33
(0.07, 1.6)
Trend test p<0.01
Men with CVD**
(n=256)
1
Ref
0.53
(0.17, 1.6)
0.42
(0.11, 1.5)
Trend test p<0.01
* adjusting for age, BMI;
** adjusting for age, BMI, aerobic activity
Out of 267 men with CVD, 256 men with CVD had valid BMI.
Out of 206 women with CVD, 199 women with CVD had valid BMI.
102
Chapter 7 Metabolic risk factor, metabolic syndrome, physical activity, depression
The metabolic syndrome is a “constellation of metabolic disturbances that
increase the risk of cardiovascular disease and type 2 diabetes84.” Adults with metabolic
syndrome are 3 times more likely to have a myocardial infarction or stroke and 2 times
more likely to die from such disease when compared to adults without metabolic
syndrome85. Among adults without prior diagnosis of diabetes mellitus, the presence of
metabolic syndrome drastically increases the risk of developing new onset diabetes86.
Metabolic syndrome carries a high risk for developing cardiovascular diseases and
diabetes.
The National Cholesterol Education Program (NCEP) Third Adult Treatment
Panel (ATP III) 2001 definition87 of “metabolic syndrome” requires that any 3 of the 5
factors are present (abdominal obesity, high triglycerides, low HDL cholesterol, high
blood pressure, and elevated fasting glucose). The abdominal adiposity risk factor is
defined as waist circumference >40" in men and > 35" in women. The triglycerides risk
factor is met if triglyceride level ≥150mg/dL. The HDL cholesterol risk factor is defined
as <40mg/dL in men and <50mg/dL in women. The blood pressure risk factor is present
when systolic blood pressure ≥130mHg or diastolic blood pressure ≥85 mmHg. The risk
factor of fasting glucose is met when glucose ≥110 mg/dL or diagnosis of diabetes is
present.
103
Separate analyses were performed for men and women with metabolic syndrome
using the NCEP criteria. Women with metabolic syndrome had a significantly higher
prevalence of depression and lower prevalence of “moderate intensity activity” than
women without metabolic syndrome. However, men with metabolic syndrome did not
have significantly different prevalence of depression and prevalence of “moderate
intensity activity” from men without metabolic syndrome.
The prevalence of muscle strengthening activity among women without metabolic
syndrome was significantly higher than that prevalence among women with metabolic
syndrome (29.6% versus 17.8%, p<0.01). The prevalence of depression was significantly
higher among women with metabolic syndrome than women without metabolic syndrome
(17.3% versus 11.3%, p<0.01).
In contrast, man with and without metabolic syndrome had similar prevalence of
“moderate intensity activity” (60.9% versus 63.7%, p=0.11) and depression (7.6% versus
8.0%, p=0.6). Using the NCEP definition of metabolic syndrome, the prevalence of
“moderate intensity activity” and the prevalence of depression did not significantly differ
between the men with metabolic syndrome and the men without metabolic syndrome.
However, the men with metabolic syndrome have significantly lower prevalence of
muscle strengthening activity than men without metabolic syndrome (22.2% versus 33%,
p<0.01). The patterns of differences between the men with metabolic syndrome and the
men without metabolic syndrome were distinct from the patterns in women.
104
Table 25. Exercise and depression among adults with and without metabolic syndrome
(as defined by NCEP criteria): NHANES 1999 to 2006 for muscle strengthening activity;
NHANES 1999 to 2012 for moderate intensity activity
No
Metabolic
Syndrome
Metabolic
Syndrome
% muscle
strengthening
activity
29.6%
17.8%
<0.001
% exercising
at moderate
intensity
activity
62.4%
49.6%
<0.001
28.9%
11.3%
4.7%
35.7%
17.3%
6.9%
<0.01
<0.01
0.002
No
Metabolic
Syndrome
Metabolic
Syndrome
% muscle
strengthening
activity
33.0%
22.2%
<0.001
% exercising
at moderate
intensity
activity
63.7%
60.9%
0.11
21.1%
8.0%
3.0%
23.2%
7.6%
2.9%
0.16
0.6
0.86
Women
Depression
PHQ≥5
PHQ≥10
PHQ≥15
Men
Depression
PHQ≥5
PHQ≥10
PHQ≥15
p
p
105
7.1 Muscle strengthening activity, depression and the Metabolic Syndrome
Among adults with metabolic syndrome or its risk factors, the association
between depression and “muscle strengthening activity” was examined while adjusting
for aerobic physical activity (NHANES 1999-2006). The fully adjusted models controlled
for age, BMI, ethnicity, CVD, cancer, arthritis, and aerobic activity. Results from the
reduced age-adjusted models were similar to the results from the fully adjusted model.
In women, large waist circumference was the only risk factor that showed a
significant inverse association (OR=0.61) between depression and “muscle strengthening
activity.” Other point estimates supported the inverse association but had wider
confidence intervals that did not reach statistical significance (Table 26).
In men with metabolic syndrome, the odds ratios for depression and muscle
strengthening activity were highly variable and none of the estimates were statistically
significant (Table 27). The lower prevalence of depression in men and the smaller subcell size contributed to the wide confidence intervals. There was an insufficient number
of men with glucose level 110 mg/dL for analysis.
106
Table 26. Odds ratios of depression* associated with muscle strengthening activity in
subgroups of women with metabolic syndrome or its risk factors: NHANES 1999-2006
Women
Subgroup of women
with
Any 1 risk factor:
Waist
circumference
High Triglycerides
Low HD
High blood pressure
# women
in
subgroup
OR
95%
OR** CI
OR
95%
OR*** CI
2240
507
1396
724
0.61
0.71
0.85
0.55
(0.38,
(0.2,
(0.54,
(0.25,
0.94)
2.4)
1.3)
1.2)
0.59
0.82
0.86
0.5
(0.38,
(0.28,
(0.56,
(0.23,
0.91)
2.4)
1.3)
1.08)
Glucose100mg/dL
Glucose  110mg/dL
430
178
0.76
1.06
(0.29, 1.9)
(0.2, 4.0)
0.9
0.9
(0.39, 2.08)
(0.2, 3.6)
Any 2 risk factors
1557
0.67
(0.39,
1.1)
0.66
(0.39, 1.1)
Metabolic
Syndrome,
any 3 risk factors
NCEP (PHQ5)
456
0.72
(0.36,
1.4)
0.7
(0.36, 1.3)
Metabolic
Syndrome,
any 3 risk factors
NCEP (PHQ10)
444
0.94
(0.36,
2.4)
0.89
(0.36, 2.2)
* Outcome is PHQ10 except otherwise stated
** Adjusted for age, BMI, ethnicity and conditions (CVD, cancer, arthritis), aerobic
activity
*** Adjusted for age
107
Table 27. Odds ratios of depression* (PHQ10) associated with muscle strengthening
activity in subgroups of men with metabolic syndrome or its risk factors: NHANES
1999-2006
Men:
Subgroup of men
with
Any 1 risk factor:
Waist
circumference
High Triglycerides
Low HD
High blood pressure
Glucose100mg/dL
Glucose110mg/dL
Any 2 risk factors
OR
95%
# men in
subgroup OR** CI
OR
95%
OR*** CI
1195
487
1009
1017
649
142
1141
0.65 (0.37, 1.1)
0.64
1.60
(0.8, 3.4)
1.60
0.69 (0.36, 1.2)
0.71
0.92 (0.52, 1.2)
0.96
0.54 (0.22, 1.3)
0.55
omitted insufficient data
0.74
(0.41, 1.3)
0.71
(0.37,
(0.8,
(0.39,
(0.56,
(0.23,
1.1)
3.2)
1.2)
1.6)
1.2)
(0.4,
1.2)
Metabolic
Syndrome,
any 3 risk factors
NCEP (PHQ5)
443
0.88
(0.48,
1.6)
0.85
(0.47,
1.5)
Metabolic
Syndrome,
any 3 risk factors
NCEP (PHQ10)
431
0.69
(0.28,
1.7)
0.66
(0.27,
1.5)
* Outcome is PHQ10 except otherwise stated
** Adjusted for age, BMI, ethnicity, CVD, cancer, arthritis, aerobic activity
*** Adjusted for age
108
7.2 Moderately intense physical activity and depression
Among adults with metabolic syndrome as defined by NCEP criteria, the severity
level of depression was found to be inversely associated with “moderately intense
physical activity.” The adjusted model controlled for age, BMI, and medical condition
(CVD, cancer, arthritis). Results of the crude age-adjusted model were similar to the
results of the fully adjusted model. In women with metabolic syndrome (at least 3 risk
factors were present), the odds ratios of mild, dysthymia, moderate, and major depression
associated with “moderate intensity activity” were 0.79, 0.72, 0.44, and 0.52,
respectively. In men with metabolic syndrome (at least 3 risk factors were present), the
odds ratios of mild, dysthymia, moderate, and major depression associated with
“moderate intensity activity” also declined steadily: 0.73, 0.5, 0.49, 0.4, respectively.
Although these point estimations of odds ratios were below one and supported the inverse
association, many of the confidence intervals were wide and did not reach statistical
significance.
In both men and women, results of separate non-parametric trend tests showed
significant declines in the odds ratios of depression severity associated with moderate
intensity physical activity. Declining trends of the odds ratios of depression associated
with “moderate intensity activity” were consistently observed in age-adjusted models and
fully adjusted models in both men and women.
Results from separate analyses of men and women with metabolic risk factor
supported the inverse dose response between the severity level of depression and
“moderately intense physical activity.” Subgroups of men and women with each specific
109
risk factors (large waist circumference, high triglyceride, low HDL cholesterol, high
blood pressure, elevated fasting glucose) were analyzed separately and the results
consistently supported the inverse association between depression and “moderately
intense activity.”
Table 28. Odds Ratios of depression severity associated with “moderate intensity
activity” in adults with NCEP metabolic syndrome: NHANES 1999-2012
Women (n=1196)
None
Mild
Dysthymia
Moderate
Major
Trend test p<0.05
Men (n= 978)
None
Mild
Dysthymia
Moderate
Major
Trend test p<0.01
OR*
OR
95%
CI
1
0.79
Ref
(0.6, 1.03)
1
0.76
Ref
(0.59, 0.98)
0.72
0.44
0.52
(0.5, 1.04)
(0.2, 0.73)
(0.23, 1.2)
0.71
0.43
0.45
(0.5, 1.01)
(0.25, 0.7)
(0.2, 1.01)
1
0.73
0.5
0.49
0.40
Ref
(0.54,
(0.29,
(0.22,
(0.11,
1
0.73
0.47
0.45
0.40
Ref
(0.54,
(0.28,
(0.2,
(0.12,
OR**
0.99)
0.81)
1.08)
1.3)
* Adjusted for age, BMI, CVD, cancer, arthritis
** Adjusted for age
110
OR 95% CI
0.98)
0.78)
1.01)
1.3)
Table 29. Odds Ratios (OR) of depression severity associated with “moderate intensity
activity” among women with waist circumference  35" and men with waist
circumference  40": NHANES 1999-2012
OR*
OR 95% CI
OR**
OR 95% CI
Women (n=3906)
None
Mild
1
0.81
Ref
(0.7, 0.9)
1
0.79
Ref
(0.6, 0.9)
Dysthymia
0.62
(0.5, 0.75)
0.6
(0.5, 0.7)
Moderate
Major
0.50
0.42
(0.38, 0.66)
(0.26, 0.66)
0.47
0.39
(0.36, 0.62)
(0.25, 0.62)
Men (n=2486)
None
mild
1
0.71
Ref
(0.59, 0.86)
1
0.68
Ref
(0.57, 0.82)
PHQ  10
0.49
(0.38, 0.63)
0.45
(0.35, 0.58)
Trend test p<0.01
Trend test p<0.01
* Adjusted for age, BMI, and medical conditions (CVD, cancer, arthritis)
** Adjusted for age
Among adults with large waist circumference, “moderate intensity activity” was
inversely associated with the severity level of depression. For women with waist
circumference  35", the odds ratios of mild, dysthymia, moderate and major depression
associated with “moderate intensity activity” were 0.81, 0.62, 0.5, and 0.42, respectively.
For men with waist circumference  40", the odds ratios of mild depression and
111
depression associated with “moderate intensity activity” were 0.71 and 0.49, respectively.
These downward trends were significant in both adjusted and reduced models.
Table 30. Odds Ratios (OR) of depression severity associated with “moderate intensity
activity” among adults with high Triglycerides 150 mg/dL: NHANES 1999-2012
OR*
OR 95% CI
OR** OR 95% CI
Women (n=796)
None
Mild
Dysthymia
Moderate
Major
Trend test p<0.01
1
1.06
0.80
0.45
0.22
Ref
(0.77,
(0.52,
(0.24,
(0.06,
1.47)
1.2)
0.84)
0.82)
1
1.03
0.75
0.4
0.18
Ref
(0.75,
(0.5,
(0.22,
(0.06,
Men (n=773)
None
mild
PHQ  10
Trend test p<0.01
1
0.80
0.49
Ref
(0.59, 1.08)
(0.33, 0.74)
1
0.81
0.47
Ref
(0.59, 1.08)
(0.32, 0.7)
1.4)
1.1)
0.74)
0.66)
* Adjusted for age, BMI, and medical conditions (CVD, cancer, arthritis)
** Adjusted for age
Among adults with elevated triglycerides (150 mg/dL), “moderate intensity
activity” was inversely associated with the severity level of depression. For women with
elevated triglyceride, the odds ratios of mild, dysthymia, moderate and major depression
associated with “moderate intensity activity” were 1.06, 0.8, 0.45, and 0.22, respectively.
For men with elevated triglyceride, the odds ratios of mild depression and depression
associated with “moderate intensity activity” were 0.8 and 0.49, respectively. Confidence
112
intervals were wide for mild depression and narrower for moderate and major depression.
Among adults with high triglycerides, the inverse dose-responses between “moderate
intensity activity” and depression were found in both adjusted and reduced models.
113
Table 31. Odds Ratios (OR) of depression severity associated with “moderate intensity
activity” among adults with low HDL: NHANES 1999-2012
(HDL cholesterol < 50 mg/dL for women, HDL cholesterol < 40 mg/dL for men)
OR*
OR 95% CI
OR**
OR 95% CI
Women (n=2058)
None
Mild
Dysthymia
1
0.71
0.57
Ref
(0.59, 0.85)
(0.44, 0.73)
1
0.7
0.57
Ref
(0.58, 0.84)
(0.45, 0.73)
Moderate
0.43
(0.30, 0.61)
0.44
(0.32, 0.62)
Major
Trend test p<0.01
0.44
(0.25, 0.83)
0.41
(0.23, 0.75)
Men (n=1387)
None
1
Ref
1
Ref
mild
0.85 (0.68, 1.06) 0.84
(0.68, 1.05)
dysthymia
0.65 (0.46, 0.93) 0.60
(0.45, 0.85)
Moderate
0.49 (0.28, 0.85) 0.43
(0.25, 0.74)
Major
0.31 (0.12, 0.77) 0.26
(0.1, 0.66)
Trend test p<0.01
* Adjusted for age, BMI, and medical conditions (CVD, cancer, arthritis)
** Adjusted for age
Among adults low HDL cholesterol, “moderate intensity activity” was inversely
associated with the severity level of depression. For women with low HDL cholesterol,
the odds ratios of mild, dysthymia, moderate and major depression associated with
“moderate intensity activity” were 0.71, 0.57, 0.43, and 0.44, respectively. For men with
low HDL cholesterol, the odds ratios of mild, dysthymia, moderate and major depression
associated with “moderate intensity activity” were 0.85, 0.65, 0.49, and 0.31,
respectively. All estimations were significant except for men with mild depression.
Results of the age-adjusted model were similar to the results of the full model.
114
Table 32. Odds Ratios of depression severity associated with “moderate intensity
activity” among adults with high blood pressure (130/ 85): NHANES 1999-2012
OR*
OR 95% CI
OR**
OR 95% CI
Women (n=1954)
None
Mild
Dysthymia
Moderate
Major
Trend test p<0.01
1
0.75
0.60
0.56
0.32
Ref
(0.6,
(0.43,
(0.35,
(0.15,
0.92)
0.82)
0.89)
0.68)
1
0.71
0.55
0.5
0.28
Ref
(0.5,
(0.4,
(0.31,
(0.13,
Men (n=1923)
None
10 to 19
 20
Trend test p<0.01
1
0.54
0.39
Ref
(0.39, 0.73)
(0.17, 0.91)
1
0.51
0.37
Ref
(0.4, 0.7)
(0.16, 0.85)
0.87)
0.76)
0.78)
0.59)
* Adjusted for age, BMI, and medical conditions (CVD, cancer, arthritis)
** Adjusted for age
Among adults with high blood pressure, “moderate intensity activity” was
inversely associated with the severity level of depression. For women with high blood
pressure, the odds ratios of mild, dysthymia, moderate and major depression associated
with “moderate intensity activity” were 0.75, 0.6, 0.56, and 0.32, respectively. For men
with high blood pressure, “moderate intensity activity” was inversely and significantly
associated with depression. The inverse dose response between “moderate intensity
activity” and depression were consistently found in the age-adjusted model and the fullyadjusted model. All estimations were statistically significant.
115
Table 33. Odds Ratios of depression severity associated with “moderate intensity
activity” among adults with fasting glucose  100 mg/dL: NHANES 1999-2012
OR*
OR 95% CI
OR**
OR 95% CI
Women (n=1338)
None
1
Ref
1
Ref
Mild
0.74
(0.62,
0.87) 0.82
(0.64,
Dysthymia
0.63
(0.50,
0.80) 0.65
(0.54,
Moderate
0.54
(0.39,
0.74) 0.52
(0.39,
Major
0.27
(0.15,
0.46) 0.30
(0.18,
Trend test p<0.01
Men (n=1518)
None
1
Ref
1
Ref
Mild
0.67
(0.55,
0.82) 0.74
(0.64,
Dysthymia
0.45
(0.33,
0.60) 0.50
(0.40,
Moderate
0.42
(0.26,
0.68) 0.45
(0.30,
Major
0.33
(0.16,
0.65) 0.39
(0.21,
Trend test p<0.01
* Adjusted for age, BMI, and medical conditions (CVD, cancer, arthritis)
** Adjusted for age
1.05)
0.79)
0.67)
0.48)
0.85)
0.63)
0.66)
0.72)
Although the NCEP threshold for fasting glucose is 110mg/dL, we analyzed the
risk factors relevant to clinically meaningful threshold values of 100 mg/dL for
prediabetes and 125mg/dL for diabetes. Among adults with high fasting glucose 100
mg/dL, the inverse dose response between “moderate intensity activity” and depression
were found in the age-adjusted model and the fully-adjusted model. For women with high
fasting glucose 100 mg/dL, the odds ratios of mild, dysthymia, moderate and major
depression associated with “moderate intensity activity” were 0.74, 0.63, 0.54, and 0.27,
respectively. For men with high fasting glucose, the odds ratios of mild, dysthymia,
moderate and major depression associated with “moderate intensity activity” were 0.67,
116
0.45, 0.42, and 0.33, respectively. All estimations were significant and all confidence
intervals of the odds ratios excluded the null value of one.
Table 34. Odds Ratios of depression severity associated with “moderate intensity
activity” among adults with fasting glucose  125 mg/dL: NHANES 1999-2012
OR*
Women (n=407)
None
Mild
Dysthymia
Moderate
Major
Trend test p<0.01
Men (n=458)
None
mild
dysthymia
Moderate
Major
Trend test p<0.01
OR 95% CI
1
0.74
0.66
0.52
0.26
Ref
(0.61,
(0.51,
(0.36,
(0.14,
1
0.65
0.43
0.47
0.29
Ref
(0.52,
(0.29,
(0.27,
(0.13,
OR**
OR 95% CI
0.89)
0.86)
0.75)
0.47)
1
0.70
0.65
0.48
0.27
Ref
(0.61,
(0.52,
(0.36,
(0.15,
0.82)
0.81)
0.65)
0.46)
0.80)
0.61)
0.83)
0.65)
1
0.70
0.50
0.47
0.34
Ref
(0.59,
(0.38,
(0.31,
(0.17,
0.82)
0.66)
0.73)
0.70)
* Adjusted for age, BMI, and medical conditions (CVD, cancer, arthritis)
** Adjusted for age
The fasting glucose threshold of 125mg/dL was classified as diabetes. Among
women with fasting glucose  125 mg/dL, the odds ratios of mild, dysthymia, moderate
and major depression associated with “moderate intensity activity” were 0.74, 0.66, 0.52,
and 0.26, respectively. For men with fasting glucose  125 mg/dL, the odds ratios of
117
mild, dysthymia, moderate and major depression associated with “moderate intensity
activity” were 0.65, 0.43, 0.47, and 0.27, respectively. All estimations were significant
and all confidence intervals of odds ratios excluded the null value of one. Adjusting for
age only yielded similarly declining trend of odds ratios of “moderate intensity activity”
associated with depression.
Results from multinomial logistic regression models show the significant inverse
declining trends between moderately intense physical activity and the severity levels of
depression, in strata of adults with metabolic syndromes (3 risk factors) as well as in
subgroups of men and women with certain metabolic risk factor. The dose-responses
between moderately intense physical activity and depression severity were significant in
adults with large waist circumference, high blood pressure, and elevated fasting serum
glucose. Among adults with high triglycerides, or low HDL cholesterol, most of the
estimations were significant except for mild depression. Adjusting for age only in the
reduced models produced similar results. The dose-responses were significantly
declining.
118
Chapter 8 Arthritis, physical activity and depression
8.1 Moderately intense physical activity and depression in adults with Arthritis
Among adults with rheumatoid arthritis or osteoarthritis, moderately intense
physical activity was inversely associated with depression. The declining trends between
moderately intense physical activity and depression severity were significant. The odds
ratios of “moderate intensity activity” among adults with merged moderate-major
depression (PHQ9  15) were lower than that in adults with dysthymia (10<= PHQ9
<=14); similarly, the odds ratios of “moderate intensity activity” among adults with
dysthymia was lower than that in adults with mild depression (5<= PHQ9 <=9). Crude
and adjusted analyses supported the same conclusion that moderately intense physical
activity was inversely associated with depression.
In adults with rheumatoid arthritis, the dose responses between moderately
intense physical activity and depression were declining, adjusting for age, body mass
index, cancer, CVD. For women with rheumatoid arthritis, the odds ratios of mild,
dysthymia, and combined moderate-major depression associated with “moderate intensity
activity” were dropping from 0.85, 0.59, to 0.32, respectively. For men with rheumatoid
arthritis, the odds ratios of mild, dysthymia, and combined moderate-major depression
associated with “moderate intensity activity” were declining from 0.72, 0.43, to 0.41,
119
respectively. The odds ratios of mild depression associated with moderately intense
physical activity were inverse and the highest. The odds ratios of combined moderatemajor depression associated with moderately intense physical activity were the lowest. In
women, all the point estimations of the odds ratios were significant except for mild
depression in women with rheumatoid arthritis.
Similarly, in adults with osteoarthritis, moderately intense physical activity was
inversely associated with the severity level of depression, while adjusting for age, body
mass index, cancer, CVD. Among women with osteoarthritis, the odds ratios of mild,
dysthymia, and combined moderate-major depression associated with moderately intense
physical activity were 0.69, 0.51, and 0.47, respectively. Among men with osteoarthritis,
the odds of mild, dysthymia, and combined moderate-major depression associated with
moderately intense physical activity were 0.65, 0.41, and 0.38, respectively. The odds of
“moderate intensity activity” declined with the severity of depression (mild > dysthymia
> combined moderate-major depression) in comparing depressed adults with nondepressed adults. For men, all the point estimations of the odds ratios were significant,
except for mild depression in men with rheumatoid arthritis. Moderately intense physical
activity was found to be beneficially and inversely associated with the severity level of
depression.
Analysis of any type of arthritis yielded similar results. Data from adults
diagnosed with either rheumatoid arthritis or osteoarthritis supported the inverse dose
response between “moderate intensity activity” and severity level of depression. Ageadjusted and unadjusted estimations were similar. In women with either rheumatoid
120
arthritis or osteoarthritis, the odds ratios of mild, dysthymia, moderate, major depression
associated with “moderate intensity activity” were 0.83, 0.62, 0.46, and 0.28 respectively.
In men with either rheumatoid arthritis or osteoarthritis, the odds ratios of mild,
dysthymia, and combined moderate-major depression associated with “moderate intensity
activity” were 0.58, 0.35, and 0.36, respectively. All estimations of odds ratios were
significant except for women with any arthritis and mild depression. Among men and
women with any type of arthritis diagnosis, results from non-parametric trend test
showed that the trends were declining significantly.
121
Table 35. Odds Ratios of depression severity associated with “moderate intensity
activity” among adults with Rheumatoid arthritis or Osteoarthritis: NHANES 1999-2012
Women,
n=2276
Depression
severity
None
Mild
Dysthymia
ModerateMajor
Combined
Rheumatoid arthritis
OR OR 95% CI
1
0.85
0.59
0.32
Ref
(0.58, 1.2)
(0.3, 0.9)
(0.17, 0.59)
Osteoarthritis
OR OR 95% CI
1
0.69
0.52
0.47
Ref
(0.52, 0.91)
(0.34, 0.79)
(0.28, 0.8)
Trend test p<0.01
* Adjusted for age, BMI, cancer, CVD.
Men, n=1580
Depression
severity
None
Mild
Dysthymia
ModerateMajor
Combined
Rheumatoid arthritis
OR OR 95% CI
1
0.72
0.43
0.41
Ref
(0.46, 1.06)
(0.23, 0.78)
(0.21, 0.79)
Trend test p<0.01
* Adjusted for age, BMI, cancer, CVD
122
Osteoarthritis
OR OR 95% CI
1
0.65
0.41
0.38
Ref
(0.47, 0.88)
(0.25, 0.66)
(0.21, 0.67)
Figure 15. Odds ratios of depression severity associated with moderately intense activity
in adults with Rheumatoid arthritis: NHANES 1999-2012
OR of depression (PHQ>=10)
Odds ratios of depression associated with moderate intensity
activity, in adults with Rheumatoid arthritis
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Mild
Dysthymia
Moderate-Major
Combined
Women, Odds ratios of depression in women with Rheumatoid arthritis
Men, Odds ratios of depression in men with Rheumatoid arthritis
Figure 16. Odds ratios of depression severity associated with moderately intense activity
in adults with Osteoarthritis: NHANES 1999-2012
Odds ratios of depression associated with moderate intensity
activity, in adults with Osteoarthritis
OR of depression (PHQ>=10)
0.80
0.70
0.60
0.50
0.40
0.30
0.20
0.10
0.00
Mild
Dysthymia
Moderate-Major
Combined
Women, Odds ratios of depression in women with Osteoarthritis
Men, Odds ratios of depression in men with Osteoarthritis
123
Table 36. Odds ratios of depression severity associated with “moderate intensity activity”
among adults with any arthritis: NHANES 1999-2012
OR*
OR 95% CI OR** OR 95% CI OR***
OR 95% CI
arthritis, n=2276
Age-adjusted
Unadjusted
Women
None
1
Ref
1
Ref
1
Ref
Mild
0.83 (0.67, 1.02)
0.76 (0.63, 0.92)
0.81 (0.67, 0.97)
Dysthymia
0.62 (0.46, 0.84)
0.61 (0.46, 0.79)
0.76 (0.58, 0.98)
Moderate
0.46 (0.31, 0.69)
0.39 (0.27, 0.56)
0.51 (0.36, 0.71)
Major
0.28 (0.14, 0.58)
0.24 (0.13, 0.46)
0.30 (0.16, 0.56)
Trend test p<0.01
arthritis, n= 1580
Age-adjusted
Unadjusted
Men
None
1
Ref
1
Ref
1
Ref
Mild
0.58 (0.44, 0.78)
0.58 (0.45, 0.75)
0.64 (0.51, 0.82)
dysthymia
0.35 (0.22, 0.55)
0.35 (0.23, 0.51)
0.43 (0.29, 0.63)
ModerateMajor
Combined
0.36 (0.21, 0.62)
0.25 (0.16, 0.41)
0.31 (0.20, 0.49)
Trend test p<0.01
* Adjusted for corticosteroid, statins, Total cholesterol, HDL, age, BMI, medical
conditions.
** Adjusted for age
*** Unadjusted
124
8.2 Muscle strengthening activity and depression in adults with Arthritis
Among adults with rheumatoid arthritis and osteoarthritis, muscle strengthening
activity was inversely associated with depression, while controlling for aerobic activity,
age and body mass index. Both kinds of arthritis (i.e. rheumatoid arthritis and
osteoarthritis) were combined to create one combined category of arthritis in order to
create sufficiently large cell count for statistical analyses. In women with any type of
arthritis, depressed women had lower odds ratio of performing muscle strengthening
activity than non-depressed women, while adjusting for aerobic activity, age and body
mass index. In men with any type of arthritis, the odds ratios of mild-dysthymia, and
moderate-major depression associated with “muscle strengthening activity” were 0.86,
0.73, respectively, while adjusting for aerobic activity, age and body mass index.
Although the point estimations supported the inverse association between muscle
strengthening activity and depression, the corresponding confidence intervals were wide
and the results were not statistically significant.
125
Table 37. Odds ratios of depression associated with muscle strengthening activity among
adults diagnosed with any arthritis (rheumatoid arthritis or osteoarthritis): NHANES 1999
to 2006.
OR*
OR 95% CI
adjusting age, BMI
Women
(n=695)
PHQ>=10
Men
(n=501)
PHQ>=10
0.58
OR 95% CI
adjusting aerobic activity, age,
BMI
(0.26, 1.3)
OR*
OR 95% CI
adjusting age, BMI
0.46
OR**
0.89
(0.47, 1.5)
OR**
OR 95% CI
adjusting aerobic activity, age,
BMI
(0.96, 1.002)
0.49
* adjusting age, BMI
** adjusting aerobic activity, age, BMI
Out of 707 women with arthritis, 695 had valid BMI.
Out of 514 men with arthritis, 501 had valid BMI.
126
(0.21, 1.1)
Chapter 9 Cancer, physical activity and depression
Physical activity and depression in adults with cancer of the breast, cervix,
uterine, prostate, colon rectum, non-melanoma, melanoma, or skin.
9.1 Moderately intense physical activity and Cancer
Among adults diagnosed with cancer, the inverse association between “moderate
intensity activity” and depression were supported by the computed odds ratios. In men
diagnosed with cancer (of the prostate, colon rectum, non-melanoma, melanoma, or skin)
and women diagnosed with cancer (of the breast, cervix, uterine, colon rectum, nonmelanoma, melanoma, or skin), the estimated odds ratios supported this inverse
association but did not reach statistical significance. The confidence intervals were wide.
Among adults with any of these aforementioned cancer, the odds of “moderate intensity
activity” in subgroups of adults with major depression was lower than the odds in
subgroups of adults with mild depression. Multinomial logistic regression models were
used to analyze the following subgroups of medical conditions for men and women:
women with cancer, women with arthritis, and women free of all three type of diseases
(cancer, CVD and arthritis); men with cancer, men with arthritis, and men free of all three
type of diseases (cancer, CVD and arthritis). For comparison purposes, results from the
arthritis chapter was relisted in the following table. Only adults with non-missing
127
physical activity data, medical condition data, and depression data were included in the
logistic analyses.
Among adults with cancer, the trend of odds ratios of “moderate intensity
activity” associated with depression was declining. There were 689 women with cancer,
2276 women with arthritis, and 3103 women free of all three conditions (no CVD and no
arthritis and no cancer). The declining trend of progressively worsening depression (mild,
dysthymia, moderate, and major depression) in women with cancer was similar to the
trend in women with arthritis. The dose responses were plotted in the same figure for
comparison. In women with cancer, the odds ratios of mild, dysthymia, moderate, and
major depression associated with “moderate intensity activity” were 0.75, 0.66, 0.61, and
0.28, respectively. However, their confidence intervals were wide and the point
estimations did not reach statistical significance. The odds of “moderate intensity
activity” declined with the severity level of depression (mild depression > moderate
depression > major depression). These trends were consistently found in the adults with
cancer, the adults with arthritis, and the adults free of all three conditions (no CVD, no
arthritis, and no cancer). In the group of cancer patients and survivors, non-parametric
trend test found that the odds ratios of depression associated with “moderate intensity
activity” were declining significantly as the level of severity of depression worsened.
128
Table 38. Odds ratios of depression severity associated with “moderate intensity activity”
among adults with cancer or arthritis: NHANES 1999-2012
(For comparison purposes, the results from the arthritis chapter was relisted here.)
Statinsadjusted
OR
Women
None
Mild
Dysthymia
Moderate
Major
cancer, n= 689
1
Ref
0.75 (0.50, 1.12)
0.66 (0.35, 1.21)
0.61 (0.27, 1.41)
0.28 (0.06, 1.3)
Arthritis, n=2276
1
Ref
0.83 (0.67, 1.02)
0.62 (0.46, 0.84)
0.46 (0.31, 0.69)
0.28 (0.14, 0.58)
Men
None
Mild
dysthymia
cancer, n= 646
1
Ref
1 (0.80, 2.6)
0.46 (0.21, 0.98)
Arthritis, n= 1580
1
Ref
0.58 (0.44, 0.78)
0.35 (0.22, 0.55)
ModerateMajor
Combined
0.5
OR 95% CI
(0.15, 1.6)
OR
OR 95% CI
0.36
(0.21, 0.62)
OR
95%
OR
CI
No CVD & No Arthritis
& No Cancer, n=3103
1
Ref
0.74 (0.60, 0.91)
0.61 (0.43, 0.82)
0.67 (0.42, 1.06)
0.28 (0.13, 0.56)
No CVD & No Arthritis
& No Cancer, n=2322
1
Ref
0.78 (0.60, 1.02)
0.52 (0.34, 0.77)
0.57 (0.33, 1.01)
* Adjusted for total cholesterol, HDL, age, BMI, medication use (statins, corticosteroids),
medical conditions
129
Figure 17. Odds ratios of depression severity (mild, dysthymia, moderate, major)
associated with moderately intense activity among women with cancer: NHANES 19992012
Women stratified by cancer, arthritis: Odds ratios of
depression severity associated with moderate intensity activity,
NHANES 1999 to 2012
Odds Ratios of Depression
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Mild
Dysthymia
Moderate
Major
Women with cancer, n= 689
Women with arthritis, n=2276
Women: No CVD & No Arthritis & No Cancer, n=3103
* Adjusted for total cholesterol, HDL, age, BMI, medication use (statins, corticosteroids),
medical conditions
In men with cancer, moderate intensity physical activity was associated with
lower odds of mild, dysthymia, and merged-moderate-major depression. Due to the low
number of men with major depression, the pool of men with moderate depression was
merged with the men with moderate depression for the purpose of analysis. There were
130
646 men with cancer, 1580 men with arthritis, and 2322 men without any of these three
medical conditions (free of CVD, arthritis, and cancer). Among men with cancer, the
odds ratios of mild, dysthymia, and moderate-major depression associated with
“moderate intensity activity” were 1, 0.46, and 0.5, respectively; in men with arthritis, the
odds ratios of mild, dysthymia, and moderate-major depression associated with
“moderate intensity activity” were 0.58, 0.35, and 0.36, respectively. For comparison, the
trend for men without any of these three medical conditions (the men without CVD and
without arthritis and without cancer) were computed and plotted next to the trend for men
diagnosed with cancer. The odds ratios of mild depression (associated with moderately
intense activity) was consistently higher than the odds ratios of dysthymia, and mergedmoderate-major depression (associated with moderately intense activity).
131
Figure 18. Odds ratios of depression severity (mild, dysthymia, moderate, major)
associated with moderately intense activity in men with cancer: NHANES 1999-2012
Odds Ratios of Depression
Men stratified by cancer, arthritis: Odds ratios of
depression severity associated with moderate intensity
activity, NHANES 1999 to 2012
1.2
1
0.8
0.6
0.4
0.2
0
Men with cancer, n= 646
Men with arthritis, n= 1580
Men: No CVD & No Arthritis & No Cancer, n=2322
132
Among women diagnosed with breast cancer, cervical cancer, or uterine cancer,
and among men diagnosed with prostate cancer, the inverse trend between depression and
moderately intense physical activity were significantly declining. In breasts cancer
patients and survivors, the odds ratios of mild, dysthymia, and combined moderate-major
depression (associated with moderately intense activity) were 0.62, 0.63, to 0.32
respectively; in women with cervical cancer or uterine cancer, the odds of mild,
dysthymia, and combined moderate-major depression (associated with moderately
intense activity) were similarly dropping through 0.89, 0.66, 0.39 respectively. For
women with breast cancer or cervical uterine cancer, the odds ratios of combinedmoderate mild depression associated with “moderate intensity activity” was lower than
the odds ratios of mild depression associated with “moderate intensity activity.” These
point estimates did not reach statistical significance. In women with breast cancer or
cervical or uterine cancer, depressed women had lower odds of moderately intense
physical activity. Among cancer patients and cancer survivors, the odds of “moderate
intensity activity” declined as the severity of depression progressively worsened.
133
Table 39. Odds ratios of depression severity associated with “moderate intensity activity”
among women with breast, cervical, uterine cancer: NHANES 1999-2012
Women
Depression
severity
Breast cancer, n=237
Cervical & Uterine
cancer, n=203
OR OR 95% CI
OR OR 95% CI
None
Mild
Dysthymia
1
0.62
0.63
Ref
(0.3, 1.3)
(0.2, 1.9)
1
Ref
0.89 (0.42, 1.9)
0.66 (0.23, 1.8)
CombinedModerateMajor
0.32
(0.05, 2.1)
0.39 (0.13, 1.1)
Trend test p<0.01
* Adjusted for age, BMI, CVD, arthritis, total cholesterol, HDL.
134
In prostate cancer patients and survivors, depression was inversely associated
with moderately intense physical activity, even though the estimated odds ratios did not
reach statistical significance. Among men with prostate cancer, the odds of “moderate
intensity activity” associated with mild depression (OR=0.93) exceeded the odds of
“moderate intensity activity” associated with depression (PHQ9  10) (OR= 0.28). Results
of age adjusted models were similar to the results from models adjusting for total
cholesterol, HDL, age, BMI, and medical conditions (presence of CVD, arthritis). The
severity level of depression were merged because there were insufficient number of men
with prostate cancer and major depression.
Table 40. Odds ratios of depression associated with “moderate intensity activity” among
men with prostate cancer: NHANES 1999-2012
Prostate cancer,
n=250
Male cancer,
n=296
Men
Depression OR
severity
OR 95% CI OR
OR 95% CI
None
Mild
PHQ  10
Ref
1
(0.39, 2.1) 0.91
(0.1, 0.9) 0.34
Ref
(0.4, 2.01)
(0.1, 0.9)
1
0.93
0.28
* Adjusted for age, BMI, CVD, arthritis, total cholesterol, HDL
135
In colon rectal cancer patients and survivors, moderately intense physical activity
was inversely associated with mild depression (OR=0.98) and dichotomized depression
(OR=0.43) in women; as well as with mild depression (OR=0.71) and dichotomized
depression (OR=0.2) in men. In adults with colon rectal cancer, further adjustment of
total cholesterol and HDL cholesterol yielded similarly declining and inverse doseresponse between depression severity and moderately intense physical activity. The
confidence intervals were wide due to missing data and the small sample sizes. Among
women and men diagnosed with colon cancer or rectum cancer, the odds ratios of mild
depression associated with moderately intense physical activity were higher than the odds
ratios of more severe depression.
Table 41. Odds ratios of depression associated with “moderate intensity activity” among
adults with colon rectal cancer: NHANES 1999-2012
Women
None
Mild
PHQ  10
Colorectal
Cancer*, n= 57
Cancer**, n= 68
OR
1
0.98
0.43
OR 95% CI
Ref
(0.2, 5.1)
(0.04, 5)
OR
1
0.71
0.20
Colorectal
Cancer*,
n= 60
OR 95% CI
Ref
(0.13, 3.8)
(0.02, 2.2)
Men
None
Mild
PHQ  10
Colorectal
OR
1
0.99
0.36
OR 95% CI
Ref
(0.3, 4.8)
(0.05, 2.8)
OR
1
0.83
0.28
Colorectal
Cancer**,
n= 65
OR 95% CI
Ref
(0.19, 3.5)
(0.04, 2.1)
* Adjusted for age, BMI, CVD & arthritis, Total cholesterol, HDL
** Adjusted for age, BMI, CVD & arthritis.
136
In men and women with non-melanoma skin cancer, moderate intensity physical
activity was inversely associated with the severity level of depression but the estimated
odds ratios were not statistically significant. The confidence intervals of these estimations
were wide. The trend of the odds ratios of “moderate intensity activity” declined with the
severity level of depression. Among women with non-melanoma skin cancer, the odds
ratios of “moderate intensity activity” among women with mild, dysthymia, and
combined-moderate-major depression were 0.61, 0.31, and 0.08, respectively. For men
with non-melanoma skin cancer, the odds of “moderate intensity activity” among men
with mild depression, and dichotomized depression (PHQ9  10) were 0.63 and 0.10,
respectively. Adjusting for total cholesterol and HDL cholesterol yielded similar results
among adults diagnosed with non-melanoma skin cancer. Results from the nonparametric trend tests were significant.
137
Table 42. Odds ratios of depression associated with “moderate intensity activity” among
adults with non-melanoma: NHANES 1999-2012
OR
OR 95% CI
OR
OR 95% CI
Women
None
Mild
Dysthymia
Non-melanoma skin
cancer*, n=125
1
Ref
0.61
(0.2, 1.7)
0.31
(0.03, 2.7)
Non-melanoma skin
cancer**, n= 128
1
Ref
0.61
(0.2, 1.7)
0.32
(0.04, 2.4)
PHQ  15
(Combined
ModerateMajor)
0.08
0.09
Men
None
Mild
PHQ  10
Non-melanoma skin
cancer*, n=156
1
Ref
0.63
(0.1, 3.5)
0.10
(0.01, 1.1)
(0.01, 1.5)
(0.01, 1.4)
Non-melanoma skin
cancer**, n=159
1
Ref
0.55
(0.1, 2.8)
0.12
(0.01, 1.3)
* Adjusted for age, BMI, CVD & arthritis, Total cholesterol, HDL
** Adjusted for age, BMI, CVD & arthritis.
138
In adults with all type of skin cancer (including melanoma, skin cancer, nonmelanoma skin cancer, and other type of unnamed skin cancer), “moderate intensity
physical activity” was inversely associated with depression. In women with any skin
cancer, the odds of “moderate intensity activity” among women with mild, dysthymia,
and combined moderate-major depression were 0.45, 0.43, and 0.24, respectively. In men
with any skin cancer, the odds of “moderate intensity activity” among men with
depression (PHQ  10) was 0.48. The confidence intervals of the estimated odds ratios
were wide and did not reach statistical significance. The results of the reduced models
were similar. The trends of the odds ratios of depression associated with moderate
intensity physical activity were declining as the severity level of depression worsened
among both men and women with melanoma and all kind of skin cancer.
139
Table 43. Odds ratios of depression associated with “moderate intensity activity” among
adults with all skin cancer: NHANES 1999-2012
OR
Women
None
Mild
Dysthymia
PHQ  15
(Combined
ModerateMajor)
Men
None
Mild
PHQ  10
OR 95% CI
OR
OR 95% CI
All types of skin cancer,
All types of skin cancer*,
Melanoma, nonn=201
melanoma**, n=207
1
Ref
1
Ref
0.45
(0.2, 0.9)
0.46
(0.2, 0.9)
0.43
(0.1, 1.5)
0.43
(0.1, 1.5)
0.24
(0.03, 1.6)
Trend test p<0.01
Non-melanoma skin
cancer*, n=156
1
Ref
0.99
(0.4, 3)
0.48
(0.15, 1.4)
0.19
(0.03, 1.1)
Non-melanoma skin
cancer**, n=159
1
Ref
0.99
(0.36, 2.7)
0.47
(0.16, 1.4)
* Adjusted for age, BMI, CVD & arthritis, Total cholesterol, HDL
** Adjusted for age, BMI, CVD & arthritis
140
9.2 Muscle strengthening activity, Depression among Cancer patients and survivors
Among adults diagnosed with certain cancer, muscle strengthening activity was
inversely and insignificantly associated with severity level of depression, while adjusting
for aerobic physical activity, age, and body mass index. Due to the limited availability of
muscle strengthening data, various types of cancer were merged into one category of
cancer. In women with breast cancer, cervical cancer, uterine cancer, colorectal cancer,
melanoma, or any kind of skin cancer, the odds ratio of depression (PHQ9  10)
(OR=0.28) was lower than the odds ratio of mild depression (OR=0.65) associated with
“muscle strengthening activity”. In men with prostate cancer, colorectal cancer,
melanoma, or any kind of skin cancer, the odds ratios of depression (OR=0.39) was lower
than the odds ratios of mild depression (OR=0.44) associated with “muscle strengthening
activity”. The confidence intervals were wide.
141
Table 44. Odds ratios of depression associated with muscle strengthening activity among
adults diagnosed with cancer: NHANES 1999-2006
Breast, Cervical, Uterine, Colorectal, Melanoma, all skin cancer*, n=253
Women
None
Mild
PHQ  10
OR*
1
0.75
0.53
OR 95% CI
OR**
Ref
1
(0.32, 1.8)
0.65
(0.18, 1.5)
0.28
OR 95% CI
Ref
(0.23, 1.8)
(0.06, 1.3)
Prostate, Colorectal, Melanoma, all skin cancer*, n=185
Men
None
Mild
PHQ  10
OR*
1
0.40
0.37
OR 95% CI
OR**
Ref
1
(0.1, 1.4)
0.44
(0.1, 1.5)
0.39
* adjusting for age, BMI
** adjusting for age, BMI, aerobic physical activity
142
OR 95% CI
Ref
(0.12, 1.5)
(0.1, 1.6)
Chapter 10 Discussion
The present study is among the first to demonstrate the beneficial inverse
association between muscle strengthening activity and depression (PHQ9  10) in a
nationally representative US sample of adults, independent of aerobic activity energy
expenditure, key demographic variables, and relevant medical conditions. Most notably,
depressed women had lower odds of performing muscle strengthening activity than nondepressed women. The inverse association was significant in all women over 18 years old,
as well as women under 50 years old. In all the men over 18 years of age, muscle
strengthening activity was significantly and inversely related to depression (PHQ9  10).
The odds ratios of performing muscle strengthening activity associated with depression in
men under 50 years old were also suggestive of inverse associations but did not reach
statistically significance, due to the smaller number of men with depression and the lower
prevalence of depression in men.
The trend of the odds ratios of the severity levels of depression (mild, dysthymia,
moderate, major depression) associated with muscle strengthening activity declined
significantly, while adjusting for aerobic activity. The inverse dose-response between
143
muscle strengthening activity and depression was consistently found in all strata of age,
and gender. Inverse associations between depression and muscle strengthening activity
were not statistically significant among adults diagnosed with arthritis, cancer, metabolic
syndrome, or cardiovascular diseases. Furthermore, various types of exercise (anaerobic,
aerobic, and combined) were associated with similarly lower odds of depression.
Depressed adults had lower odds of meeting PAGA aerobic guidelines and reporting
muscle strengthening activity. Inverse dose responses were found between the severity
level of depression and muscle strengthening activity in both gender and age strata.
The trend of the odds ratio of “moderate intensity physical activity” associated with
the severity level of depression was found to be consistently and significantly declining in
men and women. For example, the odds ratio of major depression associated with
“moderate intensity activity” was lower than the odds ratio of dysthymia. The odds ratio
of dysthymia associated with “moderate intensity activity” was in turn less than the odds
ratio of mild depression associated with “moderate intensity activity.” The analysis of
moderately intense physical activity data utilized a different set of adults than the analysis
of muscle strengthening activity data, due to survey restructuring and data availability.
Moderately intense physical activity data were available in NHANES from 1999 to 2012,
and muscle strengthening activity data were available from 1999 to 2006.
Long term duration of lipophilic statin treatment elevated the odds ratios of
depression associated with moderately intense physical activity, among women free of
cardiovascular disease as well as women diagnosed with cardiovascular disease. In
comparison, long term duration of hydrophilic statin treatment did not alter the trend of the
144
odds ratios of depression associated with moderately intense physical activity in women,
even after adjusting for CVD.
Among adults with cardiovascular disease (congestive heart failure, coronary heart
disease, angina pectoris, myocardial infarction, ischemic or hemorrhagic stroke) or arthritis
(rheumatoid arthritis, osteoarthritis), moderate intensity physical activity was found to be
significantly and inversely associated with the severity level of depression. However,
among adults with cancer (of breast, cervix, uterine, prostate, colon rectum, or skin) or
metabolic syndrome, the inverse association between depression and “moderate intensity
activity” did not reach statistical significance. The dose-response trends between
moderately intense physical activity and depression severity declined significant.
There were several study limitations that should be acknowledged. (I) First of all,
the cross-sectional nature of the NHANES survey precluded the ability to draw definitive
inferences regarding causality in the association between muscle strengthening exercise/
moderately intense physical activity and the prevention or alleviation of depression. This
study illustrated the inverse association between muscle strengthening exercises/
moderately intense physical activity and depression, but did not establish causality. We did
not identify whether muscle strengthening exercise caused depression, or whether
depression caused the participants to perform “muscle strengthening activity”. Repeated
cross sectional nature of NHANES did not allow for the establishment of causality.
Temporal causality could not be determined because data from the cross-sectional
NHANES survey refers to the prevalence of depression rather than incidence. Future cohort
145
or time-to-event studies are needed to elucidate a causal relationship and the biological
basis behind such a relationship.
(II) Another limitation was the self-reported nature of the exercise data and the
possibility of “social desirability bias”, e.g., the tendency of survey respondents to answer
questions in a manner that will be viewed favorably by members of society. Although
muscle strengthening exercise data were self-reported, the relatively neutral and nonstigmatized nature of muscle strengthening activity reduced the likelihood of data
distortion due to social desirability bias. Participants had no apparent reasons or strong
motives to misrepresent physical activity levels during the confidential data collection
process. Prior research examining physical activity and depression has utilized selfreported survey data without evidence of bias, e.g., self-reported data on aerobic physical
activity collected in NHANES showing benefit for relief of depressive symptoms have
been previously published88, 89. Alternatively, as Dr. Fristad wrote, “the overall results
would be the same if everyone exaggerated their physical activity to the same degree.” If
the percentage of depressed people over-reporting exercise was the same as (or very similar
to) the percentage of non-depressed people over-reporting exercise, then the odds ratios
results would remain the stay.
(III) Insufficient number of adults with specific medical condition and depression
has placed restrictions on the type of research questions that can posed. Sufficiently large
number of participants with non-missing physical activity data and depression data were
necessary to address research question concerning specific disease. For example, there
were six men diagnosed with congestive heart failure and major depression; hence, this
146
data would not allow the study of “muscle strengthening activity” and major depression
among men with congestive heart failure.
(IV) Missing data restricted the type of physical activity that could be addressed
using this dataset. Due to limited data availability, among adults with certain medical
conditions, depression could only be studied with respect to “moderately intense physical
activity” but not with respect to “muscle strengthening activity”. As an example, among
adults with osteoarthritis, the study of physical activity and depression could only utilize
the “moderately intense physical activity” data but not “muscle strengthening activity”
data. There were insufficient number of participants with non-missing muscle
strengthening activity data and depression data, who were also diagnosed with
osteoarthritis. In comparison, sufficiently large number of adults diagnosed with
osteoarthritis had non-missing “moderately intense physical activity” and depression data.
Similarly, missing data and small sub cell count made it impractical to address the question
of major depression and muscle strengthening activity among men diagnosed with angina.
Overall, more participants had valid and non-missing “moderately intense physical
activity” data (from 1999 to 2012) than muscles strengthening data (from 1999 to 2006).
(V) Due to survey design, NHANES dataset contained an ambiguous measure of
“moderate intensity physical activity.” The type of physical activity referred to by
“moderate intensity physical activity” was unknown. Moderately intense physical activity
could be aerobic or anaerobic activity. In reviewing the data formats before (1999 to 2006)
and after (2007 to 2012) the survey transformation, the verbiage of the aggregated
“moderately intense physical activity” items in NHANES surveys did not specify the type
147
of physical activity (aerobics or anaerobic) of such “moderately intense physical activity.”
The wordings of the NHANES survey made it impossible to know whether the aggregated
“moderate intensity physical activity” were aerobics, anaerobic, flexibility, or balance.
(VI) The unit of time referenced by “moderate intensity physical activity” was
inconclusive due to the design of NHANES. The time units of the moderately intense
physical activity varied before and after the survey transformation in 2007. Prior to the
survey redesign in 2007, “moderate intensity physical activity” was measured within the
past month (1999 to 2006); after the restructuring of the physical activity portion of the
survey, “moderate intensity physical activity” was measured within the past week (2007 to
2012). From 1999 to 2006, the aggregated data format of moderately intense physical
activity were assessed by the PAD320 field, which inquired whether the participants
engaged in moderately intense physical activity over the past month. From 2007 to 2012,
moderately intense physical activity were assessed in the unit of “a typical week.”
Certain workaround has been devised to implement consistency of data throughout
the decade, despite the lack of uniformity in the unit of time and the ambiguity found in
the type of activity referenced by “moderate intensity activity”. In order to obtain
sufficiently large sample to study specific type of medical condition, data from multiple
biennial cycles were merged to create statistically stable sub cell size count for analyses.
The liberally interpreted unit of time for moderately intense physical activity data was
weekly, whereas the conservatively interpreted unit of time was monthly. In the analyses,
the assumed unit of moderately intense physical activity data was monthly. Someone who
exercised within the past week (2007 to 2012) could be considered as someone who
148
exercised within the past month (1999 to 2006). In the merged data, “moderate intensity
physical activity” was interpreted as monthly activity because a week is a subset of a
month.
This resolved the ambiguous unit of time issue. No assumption was made
concerning the aerobic or anaerobic nature of moderately intense physical activity. Failing
to meet the NHANES definition of “moderate intensity activity” was equivalent to “a
sedentary lifestyle”.
Anaerobic muscle strengthening activity was inversely associated with depression
in the general adult population, while controlling for aerobic activity. The odds of
performing muscle strengthening activity declined with the severity level of depression, in
comparing each level of depression with no depression (mild > dysthymia > moderate
depression or major depression). However, the inverse association between muscle
strengthening activity and depression were statistically insignificant among adults
diagnosed with arthritis, cancer, metabolic syndrome, or CVD.
The inverse association between “moderate intensity physical activity” and the
severity level of depression were statistically significant in general adult and adults
diagnosed with arthritis or CVD. Their corresponding dose response trends also declined
significantly. However, in adults diagnosed with cancer or metabolic syndrome, the inverse
association between “moderately intense physical activity” and depression did not reach
statistical significance.
The long term use of lipophilic statins appeared to modify the beneficial association
between exercise and depression. Among adults on long term treatment of hydrophilic
statins, the temporal trends remained stagnant.
149
For future direction, various national longitudinal cohort health information
databases (e.g. Iceland, Norway, Sweden, or United Kingdom) could be used to investigate
whether the most “blood brain barrier permeable” lipophilic statin lovastatin had elevated
the odds ratios of depression associated with exercise at a faster pace than the least “blood
brain barrier permeable” lipophilic statin atorvastatin. Analyses of statin treatment duration
for separate lipophilic statin medications will be made possible using longitudinal cohort
datasets and sufficiently large sample size.
The public health implication of current research for older women is profound
because depression and its comorbid chronic illness (arthritis, CVD, diabetes) were
significantly more serious in US women than men90. Regular “anaerobic muscle
strengthening activity” and aerobic exercise could benefit older women, particularly older
women with chronic diseases, because “many middle aged women with chronic diseases
were sedentary and susceptible to depression 91.” After the diagnoses of chronic disease,
most women did not increase their physical activity but remained sedentary92.
Private and public health care finance administration programs could incentivize
the implementation of “supervised exercise programs” as integral components of health
care delivery because Dontje found that “physical activity was not a routine component of
the standard management of chronic diseases.” Adding supervised exercise program
(combining “anaerobic muscle strengthening activity” and aerobic exercise) to the state
worker compensation programs could benefit both the patients and the state budget because
depression was found to be a “stronger predictor of applying for work disability than
arthritic disease or response to therapy93.”
150
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