Double Jeopardy:
When ADDICTION and
MENTAL ILLNESS Coexist
Nora D. Volkow, M.D.
Director
Director
National
National Institute
Institute on
on Drug
Drug Abuse
Abuse
Prevalence of Drug
Disorders
(other than nicotine)
Prevalence of Nicotine
Addiction
100
40
80
30
Percent
25
20
15
10
60
40
Conway et al., J Clin Psychiatry, February 2006.
sion
0
Depres
ia a
r
r
ia
e
ty
b
e
b
n
i
e
d
o
d
a
i
o
o
r
i
b
r
ph ho
nx
so essi
so
ph
an
ic
i
a
i
l
a
A
r
P
D
M
d
or
ub
go ial
y D epr
d
g
t
p
ze
o
A
e
c
i
l
D
i
A
l
o
t
o
a
S
ra
nx
M
w/
ou
er
e
/
A
y
n
c
e
en
ni
cw
An Any
G
i
a
G
n
P
Pa
phreni
a
0
Schizo
5
l publi
c
20
Genera
Percent
35
Why we can not afford to further ignore
substance abuse in patients with mental illness
•
Overlapping developmental, environmental and
genetic vulnerabilities
• Drugs can trigger mental disorders in those that are
vulnerable and can exacerbate their course
•
Patients with mental illness are at greater risk for
substance abuse
•
Drugs contribute significantly to the morbidity and
mortality of patients with mental illness
Age at
Which
Marijuana
Use Is
First Initiated
Age
of Onset
of Brain
Disorders
80
70
Drug Abuse and Addiction
60
Drug Abuse
50 10 – 13
40
Obsessive-Compulsive Disorders
Years
30
20
10
0
Child
<12
Teen
12-17
Young Adult
18-25
Adult
>25
Source: Gfroerer, JC et al., SMA 02-3711, OA, SAMHSA – Data from National Survey of Drug Use and Health.
Developed from Time Magazine, January 20, 2003, p. 82
The brain undergoes major changes from
childhood through adulthood
Amygdalar Innervation of Prefrontal Cortex
Preweanling (P16)
(childhood)
Postweanling (P25)
(adolescence)
Postweanling (P65)
(adult)
`
Cunningham,
Cunningham, M.G.
M.G. et
et al,J
al,J Comparative
Comparative Neurology,
Neurology, 453:116-130,
453:116-130, 2002.
2002.
adolescent
Amygdala
adult
Prefrontal
When Reading Emotion Adults Rely More on the Frontal Cortex
While Teens Rely More on the Amygdala Deborah Yurgelon-Todd 2000.
Stressful Events Increase the Risks for some of
the Mental Illnesses and for Drug Disorders
35
10
30
Odds ratio
% s Depression
Individuals with the short
allele of the 5HT gene
25
20
15
10
8
6
4
2
5
0
Ever Addicted
0
1
2
3
4
Stressful events
Caspi et al., Science 301: 386-389 2003.
0
0 1 2 3 4 5
Adverse Childhood Experiences
PEDIATRICS 111: 564-572, 2003 (n=8603)
NRG1
BDNF
Neuroplasticity
Owen, M. J. et al. Schizophr Bull 2007 0:sbm053v1-1; doi:10.1093/schbul/sbm053
Why we can not afford to further ignore
substance abuse in patients with mental illness
•
Overlapping developmental, environmental and
genetic vulnerabilities
• Drugs can trigger mental disorders in those that are
vulnerable and can exacerbate their course
•
Patients with mental illness are at greater risk for
substance abuse
•
Drugs contribute significantly to the morbidity and
mortality of patients with mental illness
Molecular Targets for Drugs of Abuse Appear Early in
Gestation and Are Involved in Fetal Brain Development
NICOTINIC
NICOTINIC RECEPTORS
RECEPTORS
Postnatal 7
ADULT
CANNABINOID
CANNABINOID RECEPTORS
RECEPTORS
Postnatal 7
GENSAT
ADULT GENSAT
Drug Stimulation of these Receptors is Likely to Affect Development
% with schizophreniform
disorder at age 26
Adolescent Cannabis Use Effects
Adult Psychosis in Individuals with
Variations in the COMT Gene
20
no adolescent cannabis use
adolescent cannabis use
15
10
5
0
Met/Met
Val/Met
COMT genotype
Val/Val
Source: Caspi, A. et al. Biol. Psychiatry, 57: 1117-1127; 2005.
Why we can not afford to further ignore
substance abuse in patients with mental illness
•
Overlapping developmental, environmental and
genetic vulnerabilities
• Drugs can trigger mental disorders in those that are
vulnerable and can exacerbate their course
•
Patients with mental illness are at greater risk for
substance abuse
•
Drugs contribute significantly to the morbidity and
mortality of patients with mental illness
Depression Ratings for Baseline &
Weeks 1 & 2 of A Quit Attempt in
Depressed and Non-Depressed Women Smokers
Non-Depressed
Depressed
Source: Pomerleau, CS et al., Journal of Addictive Diseases, 20(10, pp. 73-80, 2001.
O
H
N
Cl
11
HN
CH3
C6 H5
11
H3 CO2C
MAO A
H
Cl
DA
MAO A
DA transporters
DA
MAO B
DA
DA
H
CONHCH2
DA
MAO B
11
H3 C
*
CH3
N
D
D
HO
11
O CH3
Cl
Cl
signal
OH
H
O
HO
HO
OH
18
F
N
C2 H5
DA receptors
Brain MAO Is Reduced by
30-40% in Smokers
MAO
MAO B
B (basal
(basal ganglia)
ganglia)
MAO
MAO A
MAO B
Brain
Brain MAO
MAO B
B&
& Smoking
Smoking Status
Status
0.3
0.2
0.1
0
non-smoker
nonnonsmokers
smokers
smokers
smokers
smoker
Fowler, J.S., Volkow, N.D., Wang, G-J., Pappas, N. et al., Nature 379, pp. 733-736, February 2, 1996.
Fowler, J.S., Volkow, N.D., Wang, G-J., Pappas, N. et al., PNAS 93, pp. 14065-14069, November 1996.
former
former L-deprenyl
L-deprenyl
smokers
smokers
Comorbidity with Mental Illness
i.e > 80% Schizophrenics Smoke
Schizophrenics have Fewer α7
AChR in Hippocampus
mRNA Levels of α7 AChR are Lower in
Schizophrenics
1.6
control
subjects
1.4
α7/β-actin
1.2
schizophrenic
patients
1.0
0.8
0.6
0.4
0.2
0.0
Controls
Medicated
Non-medicated
Perl, O et al., FASEB J, 17, pp. 1948-1950, 2003.
Freedman et al, Biol Psychiat 38, 22-33, 1995
nicotine normalizes a sensory gating abnormality
defect, found in most schizophrenics
Why we can not afford to further ignore
substance abuse in patients with mental illness
•
Overlapping developmental, environmental and
genetic vulnerabilities
• Drugs can trigger mental disorders in those that are
vulnerable and can exacerbate their course
•
Patients with mental illness are at greater risk for
substance abuse
•
Drugs contribute significantly to the morbidity and
mortality of patients with mental illness
Schizophrenic
Sibling
Standardized Incidence
3.0
2.5
2.0
1.5
1.0
0.5
0.0
Lung
Pharynx
Lichtermann et al Arch Gen Psychiatry 2001
Risks of Death by Injury Compared to Medicaid
Patients with Medical Treatment Only
aged 18-64 in 1997-1998
Odds Ratio
10
Dickey, B. et al., J of Behavioral Health Services and Research, 2004.
8
6
SUD only
Other mental + SUD
Other mental
Psychosis + SUD
0
Psychosis
60% of injury deaths were by poisoning
4
(prescription
drugs, over the counter, controlled
substances
and street drugs).
2
Comorbid Conditions Present A Variety of
Unique Treatment Challenges
Learning more about the similarities and
differences in their neurobiological, genetic and
environmental underpinnings will lead to more targeted
and effective treatment strategies