ARTICLE IN PRESS JAD-04525; No of Pages 10 Journal of Affective Disorders xxx (2010) xxx–xxx Contents lists available at ScienceDirect Journal of Affective Disorders j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j a d Research report The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders Philip Spinhoven a,b,⁎, Bernet M. Elzinga a, Jacqueline G.F.M. Hovens b, Karin Roelofs a, Frans G. Zitman b, Patricia van Oppen c, Brenda W.J.H. Penninx b,c,d a b c d Institute of Psychology, Leiden University, Leiden, The Netherlands Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands Department of Psychiatry/EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands Department of Psychiatry, University Medical Center Groningen, Groningen, The Netherlands a r t i c l e i n f o Article history: Received 5 October 2009 Received in revised form 24 February 2010 Accepted 24 February 2010 Available online xxxx Keywords: Anxiety Depression Trauma Life events Neuroticism Emotional neglect a b s t r a c t Background: Although several studies have shown that life adversities play an important role in the etiology and maintenance of both depressive and anxiety disorders, little is known about the relative specificity of several types of life adversities to different forms of depressive and anxiety disorder and the concurrent role of neuroticism. Few studies have investigated whether clustering of life adversities or comorbidity of psychiatric disorders critically influence these relationships. Methods: Using data from the Netherlands Study of Depression and Anxiety (NESDA), we analyzed the association of childhood adversities and negative life experiences across the lifespan with lifetime DSM-IV-based diagnoses of depression or anxiety among 2288 participants with at least one affective disorder. Results: Controlling for comorbidity and clustering of adversities the association of childhood adversity with affective disorders was greater than that of negative life events across the life span with affective disorders. Among childhood adversities, emotional neglect was specifically associated with depressive disorder, dysthymia, and social phobia. Persons with a history of emotional neglect and sexual abuse were more likely to develop more than one lifetime affective disorder. Neuroticism and current affective disorder did not affect the adversity– disorder relationships found. Limitations: Using a retrospective study design, causal interpretations of the relationships found are not warranted. Conclusions: Emotional neglect seems to be differentially related to depression, dysthymia and social phobia. This knowledge may help to reduce underestimation of the impact of emotional abuse and lead to better recognition and treatment to prevent long-term disorders. © 2010 Elsevier B.V. All rights reserved. 1. Introduction In understanding the causative mechanisms of depression and anxiety, it is important to acknowledge that there is a ⁎ Corresponding author. Leiden University, Institute of Psychology, Wassenaarseweg 52, 2333 AK Leiden, The Netherlands. Tel.: +31 71 5273377; fax: + 31 71 5274678. E-mail address: [email protected] (P. Spinhoven). pervasive lifetime and current comorbidity among DSM anxiety and depressive disorders (Kessler et al., 1994; Merikangas et al., 1996). Consistent with the large overlap between depression and anxiety, these disorders have a number of risk factors in common, of which adverse life events occurring in either childhood or adulthood are one of the key factors. So far, however, little is known about the general and specific contributions of these variables in depression and anxiety. 0165-0327/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2010.02.132 Please cite this article as: Spinhoven, P., et al., The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders, J. Affect. Disord. (2010), doi:10.1016/j.jad.2010.02.132 ARTICLE IN PRESS 2 P. Spinhoven et al. / Journal of Affective Disorders xxx (2010) xxx–xxx The role of childhood adversities in the etiology and maintenance of affective disorders has been repeatedly demonstrated in community studies (e.g. Kessler et al., 1997). Childhood adversities are associated with a higher risk of both onset of major depression and anxiety disorders (Kessler et al., 1997; Paolucci et al., 2001; Putman, 2003; Alloy et al., 2006). We recently also confirmed that childhood trauma – although more strongly associated to current depressive disorders – was also a significant risk factor for the presence of current anxiety disorders (Hovens et al., in press). Several community studies found that also negative life events in adulthood are associated with the onset of major depressive episodes, with first episodes being more likely to be immediately preceded by stressful life events than recurrent ones (Post, 1992; Kendler et al., 2004). Although less extensively studied, adverse life events have also been related to the onset of anxiety disorders (e.g., Brown and Harris, 1993; Kendler et al., 2003). Although most studies have described the impact of adverse life events predisposing individuals to develop both depressive and anxiety disorders, few studies examined the relative specificity of different forms of childhood adversities to these diagnoses concomitantly (Gibb et al., 2003, 2007; Harkness and Wildes, 2002; Levitan et al., 2003). A hypothesis articulated by Aaron Beck (1976) is that events related to loss might specifically result in depression, whereas others have suggested that threatening events such as sexual and physical abuse might be more related to anxiety (Brown and Harris, 1993). More specifically, Rose and Abramson (1992) proposed that emotional abuse is more likely to contribute to the development of a cognitive vulnerability to depression than either childhood physical or sexual abuse due to the fact that in case of emotional abuse the depressive cognitions are directly supplied to the child by the abuser. The limited empirical studies available partially support this theory and have shown that childhood emotional abuse is differentially related to depressive disorder (Gibb et al., 2003, 2007), depressive symptoms (Gibb and Abela, 2008; Wright et al., 2009) and social phobia (Gibb et al., 2003, 2007). Another major risk factor for the development of depression and anxiety is neuroticism. Neuroticism is one of the major temperamental basic personality traits, that appears to be stable over time during adulthood and to a large extent genetically determined (Watson et al., 2005). High levels of neuroticism are associated with increased risk for major depression and other affective disorders (Clark et al., 1994). Two models have been proposed on the relation between neuroticism and adverse life events. In the first model, adversity and neuroticism contribute independently to the vulnerability of depressive disorders, whereas in the second model it is assumed that besides increasing the overall risk of illness, higher levels of neuroticism also increase the impact of adversities (Kendler et al., 2004). Moreover, neuroticism may also be associated with a greater likelihood of exposure to adverse life events (e.g., Magnus et al., 1993), while negative life events may also have a moderate effect on neuroticism (e.g. Middeldorp et al., 2008). Limited research has examined the relationships between specific adverse life events, both in early life and adulthood and the onset of depressive and anxiety disorders, while investigating the role of neuroticism concurrently. Up till now most studies focused on only a single adult psychiatric disorder, in most cases unipolar depression, while investigating only a limited number of single adversities. Moreover, most studies did not assess current psychopathology at time of assessment of adversities and consequently report or memory bias associated with current psychopathology cannot be ruled out (McNally, 2003). The present study controlled for clustering of life adversities, psychiatric comorbidity, as well as possible bias in recall associated with current psychopathology (see Kessler et al., 1997; Alloy et al., 2006, for these methodological issues). More specifically, the goals of the present study were: (a) to compare prevalence rates of perceived childhood adversities before the age of 16 years and negative life events across the life span between controls and participants with any lifetime affective disorder; (b) to determine the relative specificity of different types of adversities to depressive versus anxiety disorders and comorbidity of depressive and anxiety disorders; and (c) to examine whether neuroticism modulates or moderates the adversity–disorder relationships. 2. Methods 2.1. Participants The data for the present study were drawn from the Netherlands Study of Depression and Anxiety (NESDA), an ongoing 8-year longitudinal cohort study aimed at examining the long-term course of depressive and anxiety disorders in different health care settings and phases of illness. A total of 2981 respondents were recruited from primary care, specialized mental health care and the community, including controls, respondents with subthreshold symptoms, and those with an anxiety and/or depressive disorder (Penninx et al., 2008). All 2981 respondents were administered a baseline assessment, which lasted on average 4 h and included assessment of psychopathology, demographic and personal characteristics, psychosocial functioning, and biomarkers. Further details about NESDA are provided elsewhere (Penninx et al., 2008). A general inclusion criterion was an age of 18 through 65 years. Excluded were patients with a primary clinical diagnosis of a psychiatric disorder not subject of NESDA which could largely affect course trajectory: psychotic disorder, obsessive compulsive disorder, bipolar disorder, or severe addiction disorder (requiring care in specialized addiction clinics). A second exclusion criterion was not being fluent in Dutch. In the total sample, 2288 participants had at least one lifetime anxiety or depressive disorder. The control group consisted of 498 screen negative primary care patients without a current or lifetime anxiety or depressive diagnosis (current minor depression included) or a current or lifetime alcohol abuse or dependence. The study protocol was approved centrally by the Ethical Review Board of the VU Medical Centre Amsterdam and subsequently by local review boards of each participating centre/institute. After full verbal and written information about the study, written informed consent was obtained from all participants. Please cite this article as: Spinhoven, P., et al., The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders, J. Affect. Disord. (2010), doi:10.1016/j.jad.2010.02.132 ARTICLE IN PRESS P. Spinhoven et al. / Journal of Affective Disorders xxx (2010) xxx–xxx 2.2. Measures 2.2.1. Depressive and anxiety disorders The diagnoses of depressive (Dysthymia and Major Depressive Disorder) and anxiety disorders (Generalized Anxiety Disorder, Social Phobia, Panic disorder with or without Agoraphobia and Agoraphobia) were established with the Composite International Diagnostic Interview (CIDI) (WHO lifetime version 2.1; Dutch version, Ter Smitten et al., 1998), which classifies diagnoses according to the DSM-IV criteria (American Psychiatric Association, 1994). The CIDI is used worldwide and WHO field research has found high interrater reliability (Wittchen et al., 1991), high test–retest reliability (Wacker et al., 2006), and high validity for depressive and anxiety disorders (Wittchen, 1994; Wittchen et al., 1989). Specially trained clinical research staff conducted the CIDI interview. 2.2.2. Neuroticism Neuroticism was measured with the NEO Five-Factor Inventory (NEO-FFI) (Costa and McCrae, 1992, 1995; Dutch version, Hoekstra et al., 1996). Cronbach's alpha for the subscale of Neuroticism, composed of 12 items, in the present study was .75. 2.2.3. Childhood adversities Childhood life events and childhood traumas were assessed retrospectively using a semi-structured childhood trauma interview, previously used in the Netherlands Mental Health Survey and Incidence Study (NEMSIS) (de Graaf et al., 2004a,b). In this interview, respondents were asked whether they had experienced before the age of 16 years one of the following types of trauma: emotional neglect, psychological, physical and/or sexual abuse. Emotional neglect was described as: ‘Nobody ever listened to you at home, your problems were ignored, you had the feeling not being able to find any attention or support from your parents’. Psychological abuse was described as: ‘You were verbally abused, unjustly punished, your brothers and sisters were favored — but no bodily harm was done’. Physical abuse was defined as: ‘Being kicked, hit with or without an object, or being physically maltreated in any other way’. Sexual abuse was defined as: ‘Being touched sexually by anyone against your will, or being forced to touch anyone sexually’. After an affirmative answer to these probing questions more specific details on the frequency of these events and the perpetrators involved were asked for. Frequency of occurrence was recorded as: never, once, sometimes, regularly, often, or very often. Additional questions regarding important negative childhood life events prior to age 16 were asked including divorce of parents, being placed in a child home or juvenile prison, being raised in a foster family or regularly running away from home. For sake of comparison with the scoring of negative life events by the LTE-Q (see below) childhood adversities were scored dichotomously as absent (i.e. never happened) or present (i.e. happened once, sometimes, regularly, often or very often). 2.2.4. Negative life events across the life span Twelve negative life events were assessed using the List of Threatening Events Questionnaire (LTE-Q; Brugha et al., 1985; Brugha and Cragg, 1990). These events reflect the 3 presence of life stressors across the life span until the year preceding the baseline assessment such as serious illness and injury, death of close friend or relative, unemployment, major financial loss, and loss of important relationships. The LTE-Q has good test–retest reliability (kappa = .78 to 1.0 on all categories except “something you valued was lost or stolen,” where kappa = .24), high agreement between participant and informant ratings (kappa = .7 to .9), as well as good agreement with interview-based ratings (sensitivity = .89; specificity = .74; Brugha and Cragg, 1990). 2.3. Statistical methods First, differences in prevalence rates of adversities between controls and participants with any lifetime affective disorder were analyzed with logistic regression analyses with the association expressed as an odds ratio (OR). When certain life adversities were reported by at least 10% of the participants with a lifetime affective disorder, they were retained for further analysis. In order to analyze the relative specificity of different adversities to different anxiety and depressive diagnoses, we predicted the presence or absence of a particular diagnosis on the basis of adversities within the total sample of participants with lifetime affective disorders (Gibb et al., 2007). A benefit of this analysis is that it includes a built-in psychiatric control group. To guard against multicollinearity, the Variance Inflation Factor (VIF) score for each variable in each predictor model was examined. We used the arbitrary but stringent rules of thumb cut-off criterion of 2.5 for deciding when a given independent variable displays “too much” multicollinearity (O'Brien, 2007). Following this, multivariate associations (ORs) of adversities with individual anxiety and depressive diagnoses, controlling for demographic variables (i.e., age, gender and education level) (Model 1), comorbid disorders (Model 2) and comorbid disorders plus clustering of life adversities (Model 3) were calculated with logistic regression analyses. In addition, in order to analyze the effect of adversities on comorbidity, the estimated number of affective disorders on the basis of adversities was calculated with Generalized Estimating Equations (GEE) while controlling for demographic variables and other adversities. GEE for logistic regression is suitable for analyzing non-independent clustered data (Hanley et al., 2003), such as caseness of an individual within a cluster of various anxiety and depressive diagnostic categories, while controlling for covariates and therefore suitable to analyze the association of the prevalence of any disorder with adversities. In addition, neuroticism and current affective disorder were forced into separate GEE prediction models in order to investigate whether adversities independently predict prevalence estimates of anxiety and depressive disorders over and above these variables. Moreover, it was investigated whether neuroticism or current affective disorder moderated the association of adversities with the prevalence of anxiety and depressive disorders. In separate GEE analyses controlling for demographic characteristics and each life adversity, these possible moderator variables and 17 dummy variables representing the interaction of these moderator variable with each of the adversities were entered simultaneously. The resulting model was reduced by removing non-significant Please cite this article as: Spinhoven, P., et al., The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders, J. Affect. Disord. (2010), doi:10.1016/j.jad.2010.02.132 ARTICLE IN PRESS 4 P. Spinhoven et al. / Journal of Affective Disorders xxx (2010) xxx–xxx interaction terms (i.e. p b .01) one at a time, after which the model was rerun. For the GEE analyses it was necessary to use categorical scores for neuroticism and split the continuous scores for neuroticism into three categories using the (approximate) 33 and 66 percentile. These analyses were repeated with respect to specific anxiety and depressive disorders using logistic regression analysis while also controlling for comorbidity among disorders. For sake of comparison with the scoring of more discrete negative life events by the LTE-Q, we firstly analyzed childhood adversities likewise scored dichotomously as absent (i.e. never happened) or present (i.e. happened once, sometimes, regularly, often or very often) (see above). However, it could be argued that the impact of childhood adversities on affective disorders depends on the chronicity of these adversities. Consequently, we also assessed whether there exist any dose–response relationships between specific childhood adversities and affective disorders by analyzing frequency of childhood adversities besides presence of childhood trauma using GEE. Analyses were carried out by SPSS (version 16.0). A relatively strict significance level of .01 was used for all comparisons. Although setting alpha smaller than the usual .05 level decreases our power to detect small effects, a stricter level is needed for controlling the family wise error rate when multiple comparisons are made. Given our large sample of participants, the statistical power was sufficient for detecting moderate to large effects, which are clinically more relevant. All tests were two-tailed. 3. Results 3.1. Demographic and clinical characteristics Complete data on personality traits, childhood adversities and negative life events were available for 2288 of the 2328 participants with at least one lifetime anxiety or depressive disorder (98.3%). The number of lifetime affective disorders was 2.33 (SD = 1.18) with only 30.6% of the participant having (had) only one anxiety or depressive disorder. At the time of testing 616 participants (26.9%) were in remission and had no current 6-month anxiety or depressive disorder. 3.2. Prevalence of childhood adversities and negative life events The prevalences of reported childhood adversities and negative life events in controls and participants with at least one lifetime affective disorder are shown in Table 1. Participants with lifetime affective disorders reported a significantly higher prevalence for most of the childhood adversities and negative life events across the life span compared to controls. Although 92 of the 136 point-biserial correlations (67.6%) among adversities were significant at p b .01 (data not shown), only 4 of the 136 associations had a medium to large effect size (of at least r = .30): emotional neglect was associated with both psychological (r = .57) and physical abuse (r = .39), psychological abuse with physical abuse (r = .53) and being fired from a job with looked for job without result (r = .42). In accordance with these results, the Table 1 Bivariate associations (odds ratio's) of childhood adversities and negative life events with presence of at least one lifetime anxiety and depressive disorder. Variables Controls (n = 498) n Childhood adversity to age 16 Divorce parents Placed in a childhome a Placed in juvenile prison a Raised in foster family a Regularly ran away from home a Emotional neglect Psychological abuse Physical abuse Sexual abuse LTE-Q Seriously ill, wounded or victim of violence Seriously ill, wounded or victim of violence of family member Parent, child, brother or sister died Friend or family member died Separation of partner A friendship with close friend or family member ended Serious problem with close friend, family member or neighbor Became unemployed or looked for a job without result Fired from job Serious financial problems Contact with police or justice by misdemeanor Something worthwhile or money was stolen or lost Any disorder (CIDI) (n = 2288) Odds ratio % n % 56 13 1 19 11 94 56 32 63 11.2 2.6 .2 3.8 2.2 18.9 11.2 6.4 12.7 303 98 8 78 117 1033 667 368 471 13.2 4.3 .3 3.4 5.1 45.1 29.2 16.1 20.6 1.205 1.669 1.744 .890 2.386 ⁎⁎ 3.538 ⁎⁎⁎ 3.248 ⁎⁎⁎ 2.791 ⁎⁎⁎ 1.790 ⁎⁎⁎ 167 350 296 332 180 152 102 104 75 50 65 182 33.5 70.3 59.4 66.7 36.1 30.5 20.5 20.9 15.1 10.0 13.1 36.5 910 1481 1196 1428 1200 970 719 653 505 509 324 741 39.8 64.7 52.3 62.4 52.4 42.4 31.4 28.5 22.1 22.2 14.2 32.4 1.309 ⁎⁎ .776 ⁎ .747 ⁎⁎ .830 1.949 ⁎⁎⁎ 1.675 ⁎⁎⁎ 1.779 ⁎⁎⁎ 1.513 ⁎⁎⁎ 1.597 ⁎⁎⁎ 2.564 ⁎⁎⁎ 1.099 .832 Note: CIDI = Composite Interview Diagnostic Instrument; LTE-Q = List of Threatening Events Questionnaire. ⁎ p b .05. ⁎⁎ p b .01. ⁎⁎⁎ p b .001. a These events were not further analyzed because it was reported by less than 10% of the participants with an affective disorder. Please cite this article as: Spinhoven, P., et al., The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders, J. Affect. Disord. (2010), doi:10.1016/j.jad.2010.02.132 ARTICLE IN PRESS P. Spinhoven et al. / Journal of Affective Disorders xxx (2010) xxx–xxx VIF for each adversity varied from 1.04 to 1.82 and was far below our cut-off criterion of 2.5. 3.3. Adversity–disorder relationships, controlling for demographic variables As a first step, we analyzed the associations (odds ratio's (ORs)) of childhood adversities and negative life events across the life span with lifetime anxiety and/or depressive disorders controlling for demographic variables with GEE and logistic regression analysis among participants with at least one lifetime depressive or anxiety disorder (Model 1) (see Table 2). The ORs of 10 out of the 17 life adversities were statistically significant as predictor of the number of affective disorders (p b .01). The ORs of 4 out of the 5 childhood adversities (i.e., emotional neglect, psychological, physical and sexual abuse) were statistically significant as predictor of both the presence of any depressive and the presence of any anxiety disorder. Moreover, having been seriously ill, wounded or a victim of violence and serious financial problems predicted the presence of any depressive disorder. Logistic regressions analyses showed that the consistency of ORs of childhood adversities with individual depressive and anxiety disorders (53.3% of the 30 ORs is statistically significant) is greater than of negative life events (18.0% of the 72 ORs is statistically significant). 3.4. Adversity–disorder relationships, controlling for demographic variables, comorbid disorders and other life adversities As a second step, we used GEE and logistic regression analyses to determine the associations (ORs) of childhood adversities and negative life events with lifetime anxiety and depressive diagnoses, controlling for demographic variables and comorbid disorders (Model 2). Although 69.4% of the participants had comorbid psychiatric disorders, there were no multicollinearity problems since the VIF values for each predictor varied from 1.04 to 1.13 and were far below our stringent cut-off criterion of 2.5. After statistically controlling for comorbidity of any anxiety disorder, it appeared that emotional neglect and psychological, physical and sexual abuse were still predictive of any lifetime depressive disorder and in addition that controlling for any depressive disorder these same childhood traumas were also predictive of any lifetime anxiety disorder (data not shown). Next, we also statistically controlled for other life adversities using GEE and logistic regression analyses (Model 3) (see Table 3). After introducing control for overlap among adversities, the ORs of only 2 of the 10 individual adversities predictive of the number of affective disorders in Model 1 remained statistically significant: emotional neglect (OR = 1.223, p b .001) and sexual abuse (OR = 1.122, p b .001). Moreover, emotional neglect proved to be the only significant predictor of any depressive disorder (OR = 2.043, p b .001) and any anxiety disorder (OR = 1.573, p b .001). Further exploration of the ORs for the individual anxiety and depressive diagnoses shows that the majority of the ORs for individual adversities are greatly attenuated. Compared to the results of Model 1, only 5 of the previously 29 significant ORs remained statistically significant predictors of an individual anxiety or depressive disorder. The overall effect as found with GEE appears to be mainly due to the association of emotional neglect with dysthymia (OR = 1.493, 5 p b .001), major depression (OR = 1.627, p b .001), and social phobia (OR = 1.473, p b .001) and the association of sexual abuse with dysthymia (OR = 1.545, p b .001). 3.5. Effect of neuroticism on adversity–disorder relationships Because neuroticism may be associated with a greater likelihood of exposure to adverse life events, the association of this variable with perceived childhood adversities and negative life events was analyzed with point-biserial correlation coefficients. Neuroticism showed a small to moderate positive association with the following three childhood traumas: emotional neglect (r = .220, p b .001), psychological (r = .172, p b .001) and physical abuse (r = .148, p b .001), but had an association smaller than r = .10 with all other adversities indicating that neuroticism as a putative moderator variable was only weakly associated with the predictor variables for life adversities providing a potentially clearly interpretable interaction term (Baron and Kenny, 1986). Next, we performed a GEE to analyze whether neuroticism moderated the relationship of childhood adversities and negative life events with lifetime anxiety and depressive diagnoses. In addition to the demographic variables as covariates and all the individual life adversities as predictor variables, 17 dummy variables representing the interaction of neuroticism with each of the adversities were entered simultaneously. The resulting model with 37 terms was subsequently reduced by firstly removing non-significant interaction terms (i.e. p b .01) one at a time, after which the model was rerun. None of the interaction terms proved to be predictive of the number of anxiety and depressive disorders. In the final model neuroticism was a strong predictor of the number of affective disorders. Compared to participants with low neuroticism, the OR for participants with medium neuroticism to have more than one affective disorders was 1.37 (p b .001) and for participants with high neuroticism 1.84 (p b .001). Of note is that in the final prediction model controlling for demographic variables, neuroticism and all other adversities, the ORs for both emotional neglect (OR = 1.13, p b .001) and sexual abuse (OR = 1.12, p b .001) remained statistically significant, but the OR for a family member being ill, wounded, or victim of violence now also became significant. In separate logistic regression analyses of each individual anxiety and depressive disorder, controlling for demographic characteristics, comorbid anxiety and depressive disorders, adversities and neuroticism, also none of the interaction terms proved to be predictive, while neuroticism predicted each of the depressive and anxiety disorders (OR's varying between 1.232 (p b .01) for agoraphobia to 1.844 (p b .001) for social phobia) (data not shown). 3.5.1. The effect of current affective disorder on adversity– disorder relationships Next, we performed a similar GEE to analyze whether current affective disorder moderated the relationship of childhood adversities and negative life events with lifetime anxiety and depressive diagnoses. In addition to the demographic variables as covariates and all the individual life adversities as predictor variables, 17 dummy variables representing the interaction of current affective disorder with each of the adversities were entered simultaneously. The resulting model with 37 terms was subsequently reduced by Please cite this article as: Spinhoven, P., et al., The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders, J. Affect. Disord. (2010), doi:10.1016/j.jad.2010.02.132 6 Lifetime disorders (CIDI) Childhood adversity to age 16 Divorce parents Emotional neglect Psychological abuse Physical abuse Sexual abuse LTE-Q Seriously ill, wounded or victim of violence Seriously ill, wounded or victim of violence of family member Parent, child, brother or sister died Friend or family member died Separation of partner A friendship with close friend or family member ended Serious problem with close friend, family member or neighbor Became unemployed or looked for a job without result Fired from job Serious financial problems Contact with police or justice by misdemeanor Something worthwhile or money was stolen or lost Dysthymia Depression GAD Social phobia Panic disorder Agoraphobia Any depressive disorder Any anxiety disorder Number of disorders (n = 648) (n = 1887) (n = 763) (n = 892) (n = 860) (n = 281) (n = 1935) (n = 1738) (n = 2288) 1.459 ⁎⁎ 2.281 ⁎⁎⁎ 2.111 ⁎⁎⁎ 1.962 ⁎⁎⁎ 2.109 ⁎⁎⁎ .998 1.907 ⁎⁎⁎ 1.938 ⁎⁎⁎ 1.615 ⁎⁎ 1.524 ⁎⁎ 1.215 1.521 ⁎⁎⁎ 1.476 ⁎⁎⁎ 1.417 ⁎⁎ 1.310 ⁎ 1.006 1.593 ⁎⁎⁎ 1.412 ⁎⁎⁎ 1.286 ⁎ 1.422 ⁎⁎⁎ .973 1.136 1.210 ⁎ 1.377 ⁎⁎ 1.236 ⁎ 1.223 1.341 ⁎ 1.215 1.147 1.161 1.009 2.121 ⁎⁎⁎ 2.102 ⁎⁎⁎ 1.664 ⁎⁎ 1.478 ⁎⁎ 1.151 1.600 ⁎⁎⁎ 1.569 ⁎⁎⁎ 1.499 ⁎⁎ 1.489 ⁎⁎ 1.052 1.329 ⁎⁎⁎ 1.300 ⁎⁎⁎ 1.257 ⁎⁎⁎ 1.234 ⁎⁎⁎ 1.528 ⁎⁎⁎ 1.216 1.358 ⁎⁎ 1.244 1.318 ⁎⁎ 1.026 1.209 ⁎ 1.177 1.144 1.110 .996 1.078 1.405 ⁎⁎ 1.210 1.171 1.243 ⁎ 1.143 ⁎⁎⁎ 1.096 ⁎⁎ 1.246 .889 1.247 ⁎ 1.317 ⁎⁎ 1.366 ⁎⁎ 1.468 ⁎⁎ 1.003 1.227 1.270 ⁎ 1.283 ⁎ 1.154 .928 1.210 ⁎ 1.168 1.339 ⁎⁎ 1.044 1.023 1.138 1.337 ⁎⁎⁎ .993 .996 1.094 1.064 1.222 ⁎ 1.088 .974 1.224 .942 .984 1.077 1.340 ⁎ .918 1.301 ⁎ 1.225 1.209 1.103 .995 1.065 1.272 ⁎ 1.131 1.098 ⁎⁎ 1.030 1.079 ⁎ 1.131 ⁎⁎⁎ 1.101 ⁎⁎ 1.635 ⁎⁎⁎ 1.496 ⁎⁎⁎ 1.440 ⁎⁎⁎ .971 1.156 1.460 ⁎⁎ .808 1.259 1.289 ⁎⁎ 1.132 1.202 .994 .947 1.223 1.121 1.135 1.204 1.202 1.261 ⁎ 1.076 .992 1.214 .991 .947 .950 .975 1.081 1.170 1.060 1.286 1.536 ⁎⁎ .903 1.315 ⁎ 1.213 1.145 1.070 1.331 .845 1.060 1.097 ⁎ 1.123 ⁎⁎⁎ 1.014 1.027 1.003 1.268 ⁎ Note: CIDI = Composite Interview Diagnostic Instrument; GAD = Generalized Anxiety Disorder; LTE-Q = List of Threatening Events Questionnaire. ⁎ p b .05. ⁎⁎ p b .01. ⁎⁎⁎ p b .001. ARTICLE IN PRESS Variables P. Spinhoven et al. / Journal of Affective Disorders xxx (2010) xxx–xxx Please cite this article as: Spinhoven, P., et al., The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders, J. Affect. Disord. (2010), doi:10.1016/j.jad.2010.02.132 Table 2 Multivariate associations (expressed in odds ratios) of childhood adversities and negative life events with different lifetime anxiety and depressive diagnoses, controlling for age, gender and education among subjects with at least one lifetime depressive or anxiety disorder (n = 2288) (Model 1). Lifetime disorders (CIDI) Childhood adversity to age 16 Divorce parents Emotional neglect Psychological abuse Physical abuse Sexual abuse LTE-Q Seriously ill, wounded or victim of violence Seriously ill, wounded or victim of violence of family member Parent, child, brother or sister died Friend or family member died Separation of partner A friendship with close friend or family member ended Serious problem with close friend, family member or neighbor Became unemployed or looked for a job without result Fired from job Serious financial problems Contact with police or justice by misdemeanor Something worthwhile or money was stolen or lost Dysthymia Depression GAD Social phobia Panic disorder Agoraphobia Any depressive disorder Any anxiety disorder Number of disorders (n = 648) (n = 1887) (n = 763) (n = 892) (n = 860) (n = 281) (n = 1935) (n = 1738) (n = 2288) 1.183 1.49*** 1.196 1.065 1.54*** .766 1.627*** 1.260 .970 1.175 1.039 1.176 1.091 1.005 1.003 .855 1.473*** 1.087 .865 1.198 .947 .993 1.045 1.342 1.155 1.089 1.355 1.095 1.140 1.154 .773 2.043*** 1.534* .851 1.277 .918 1.573*** 1.332 .998 1.346* .958 1.223*** 1.098* 1.018 1.122*** 1.188 1.131 1.209 1.215 1.173 .957 1.100 1.165 1.024 1.112 1.003 1.139 1.286 1.307* 1.146 1.306* 1.081* 1.081* 1.102 .845 .993 1.005 1.059 1.338* .999 1.094 1.128 1.057 1.117 .935 1.116 .992 1.23* .991 .986 1.026 1.260* .827 .960 1.166 .980 1.148 .990 .932 1.303 .934 1.000 1.051 1.298 .836 1.146 1.115 1.018 1.096 .924 1.004 1.188 .969 1.067 1.008 1.023 1.061 1.018 1.330* 1.146 1.079 .819 1.146 .739* 1.126 1.270 .698* 1.095 1.132 .929 1.010 .918 .845 1.093 .945 1.008 1.076 .965 .893 1.263 .992 1.227 .705*** .865 1.090 .930 1.066 1.030 .829 1.226 1.307 .771 1.071 1.068 1.080 .975 1.243 .773* .977 1.055 1.042 .947 .973 Note: *p b .05; ***p b .001; CIDI = Composite Interview Diagnostic Instrument; GAD = Generalized Anxiety Disorder; LTE-Q = List of Threatening Events Questionnaire. a Controlling for other disorders took only place in predicting individual diagnoses and not in predicting number of diagnoses using GEE. ARTICLE IN PRESS Variables P. Spinhoven et al. / Journal of Affective Disorders xxx (2010) xxx–xxx Please cite this article as: Spinhoven, P., et al., The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders, J. Affect. Disord. (2010), doi:10.1016/j.jad.2010.02.132 Table 3 Multivariate associations (expressed in odds ratio's) of childhood adversities and negative life events with different lifetime anxiety and depressive diagnoses, controlling for age, gender and education, other adversities and comorbid disorders a among subjects with at least one lifetime depressive or anxiety disorder (n = 2288) (Model 3). 7 ARTICLE IN PRESS 8 P. Spinhoven et al. / Journal of Affective Disorders xxx (2010) xxx–xxx firstly removing non-significant interaction terms (i.e. p b .01) one at a time, after which the model was rerun. None of the interaction terms for current disorder X adversity were predictive of the estimated number of lifetime anxiety and depressive disorders, suggesting that current symptomatology does not significantly affect adversity–disorder relationships and that the adversity–disorder relationships are consistent for current disorders as well as remitted lifetime disorders. In the final prediction model controlling for demographic variables and other adversities, besides current affective disorder only emotional neglect (OR = 1.19, p b .001) and sexual abuse (OR = 1.11, p b .01) reached the αi level of p b .01. In separate logistic regression analyses of each individual anxiety and depressive disorder, while controlling for demographic characteristics, comorbid anxiety and depressive disorders, adversities and current affective disorder, also none of the interaction terms proved to be predictive (data not shown). 3.5.2. The effect of frequency of childhood trauma on adversity– disorder relationships Finally, we assessed whether analyzing frequency (instead of presence) of childhood trauma would critically affect outcome. To this end trauma scores were categorized from 0 to 2 (0 ‘never happened’, 1 ‘happened once’ or ‘sometimes’, 2 ‘happened regularly’, ‘often’ or ‘very often’). Performing a GEE analysis controlling for demographic variables and other adversities (i.e. divorce of parents and the twelve negative life events on the LTE-Q), of the four childhood traumas investigated only regular or (very) frequent emotional neglect (OR = 1.24, p b .001) and sexual abuse (OR = 1.21, p b .01) reached the αi level of p b .01, while incidental or infrequent emotional neglect (OR = 1.16) and sexual abuse (OR = 1.10) were no longer statistically significant (p b .05). Moreover, in analyzing frequency instead of presence of psychological and physical abuse, these childhood traumas again proved to be unrelated to number of affective disorders while controlling for demographic variables and other adversities. 4. Discussion 4.1. Specificity of different types of adversities to depressive and anxiety disorders A main goal of this study was to examine the relative specificity of particular childhood adversities and negative life events across the life span to different depressive and anxiety disorders. Our study demonstrates that the prevalence of perceived adversities in childhood and adulthood was higher in persons with at least one lifetime affective disorder compared to controls. Among persons with a lifetime affective disorder, different types of childhood trauma and the majority of the negative life events were associated with each of the affective disorders and with a higher comorbidity of affective disorders. However, this overall picture changed after statistically controlling for comorbidity of affective disorders and clustering of life adversities in our study sample. Our most important findings are the following: First, the association of childhood adversities with affective disorders appears to be greater than the association of negative life events across the life span with affective disorders. Secondly, childhood traumas are found to be characteristic of both any lifetime depressive disorders and any lifetime anxiety disorders, although the strength of the association of childhood traumas with depressive disorders seems somewhat stronger than with anxiety disorders. Thirdly, in particular emotional neglect was specifically related to dysthymia, major depressive disorder and social phobia. Fourthly, participants with a history of emotional neglect and to a lesser extent sexual abuse are more likely to develop more than one lifetime affective disorder. These results support previous notions that negative experiences during childhood in particular may contribute to vulnerability for developing various types of affective disorders across the life span (Beck, 1976; Bowlby, 1973, 1980; Heim and Nemeroff, 2001). However, the magnitude of the attenuated associations is relatively small (ORs of around 1.5). In particular childhood emotional neglect, which is more closely associated with loss than with danger/threat, showed a differential relationship with dysthymia, depressive disorder, but also social phobia. Of note is that this association was greatly reduced after correction for other childhood adversities, because neglect proved to be strongly related with psychological abuse in particular. These findings are consistent with previous literature indicating that emotional neglect/abuse is specifically related to depressive disorder (Gibb et al., 2003, 2007) and depressive symptoms (Gibb and Abela, 2008; Wright et al., 2009), but also with social phobia (Gibb et al., 2003, 2007). Emotional neglect and abuse both constitute forms of psychological maltreatment in nurturing relationships between children and their caregivers characterized by patterns of harmful interactions, requiring no threatening physical contact with the child as in sexual and physical abuse (Glaser, 2002). In contrast with several authors (e.g., Brown and Harris, 1993), childhood traumas characterized by danger/threat such as physical and sexual abuse were not differential predictors of anxiety disorders. Although both types of childhood trauma were related to either depressive and anxiety disorders, the associations with anxiety disorders disappeared after clustering with other adverse life events were taken into account. Given, the high intercorrelations among childhood neglect and trauma, we speculate that the associations of sexual and physical abuse with anxiety disorders are largely due to the cooccurrence with emotional neglect/abuse. It could be argued that the association of childhood adversities with affective disorders primarily reflects chronic conditions whereas the association with negative life events across the life span reflects more discrete events. In accordance with previous studies (e.g. Bulik et al., 2001; Hovens et al., in press; Kessler et al., 1997; MacMillan et al., 2001; Wiersma et al., 2008) we indeed found a dose–response relationship between neglect and sexual abuse and number of affective disorders suggesting that the greater association of childhood adversity versus negative life events with affective disorders may be due to differences in the chronicity of the adversities (chronic versus episodic) rather than to differences in the timing of stressor exposure (childhood versus later life). 4.2. Effect of neuroticism on adversity–disorder relationships A further aim of the present study was to examine whether neuroticism or current psychopathology moderate the Please cite this article as: Spinhoven, P., et al., The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders, J. Affect. Disord. (2010), doi:10.1016/j.jad.2010.02.132 ARTICLE IN PRESS P. Spinhoven et al. / Journal of Affective Disorders xxx (2010) xxx–xxx adversity–disorder relationships. Although including neuroticism in our predictions attenuated the significant association of childhood trauma with affective disorders, it did not remove it. Childhood trauma appears to be independently associated with affective disorders even after accounting for the overlap with neuroticism. Moreover, no evidence was found that neuroticism moderated the association of childhood trauma with one of the anxiety or depressive disorders. So, we failed to replicate previous study results in depressive disorder (e.g. Kendler et al., 2004) consistent with a model, which assumes that neuroticism moderates adversity–disorder relationships and consequently that higher levels of neuroticism will also increase the impact of adversities. Our data on the presence or absence of adversity, however, might be too crude and imprecise to allow for detections of differences depending on level and context of stress. Moreover, we were able to study the effect of current affective state on the assessment of lifetime affective disorders and adversities, because a substantial part of our study participants were remitted at the time of assessment. We found no indications for memory distortion or inflation (McNally, 2003) associated with psychopathology as current affective state did not significantly moderate the association of child trauma with lifetime affective disorder indicating that the association is consistent for current disorders as well as remitted lifetime disorders. These results concur with previous studies showing that adults' recall of in particular specific childhood events such as neglect and abuse is relatively accurate and not critically affected by mood state (for a review, see Brewin et al., 1993). 9 grained analyses of context, severity and in particular temporal order; and (e) the absence of systematic assessments for posttraumatic stress disorder (PTSD). Although adversity is an important predictor of a great many other disorders than PTSD, the association of childhood adversity with any anxiety disorder may have been underestimated in the present study because sexual and physical abuse may result in PTSD as an anxiety disorder, while the experience of neglect and emotional abuse is not sufficient for fulfilling criterion A of the DSM-IV diagnosis of PTSD and is also more strongly related to dysthymia and depression. 4.4. Theoretical and clinical implications A fruitful area for further research is studying mechanisms underlying specific adversities–affective disorders relationships with a greater emphasis on emotional abuse and neglect. Both types of trauma have been the least studied of all types of childhood trauma, however the most prevalent and possibly the ones with the highest impact on the further development of the child (Teicher et al., 2006; Egeland, 2009; Gilbert et al., 2009). Further research into a negative cognitive style (for a review, see Alloy et al., 2006) and the development of emotion dysregulation (e.g., Maughan and Cicchetti, 2002) could help to elucidate adversity–disorders relationships. Moreover, informing parents, teachers, health care workers and the general public about the possible detrimental impact of emotional abuse may help to reduce underestimation of the impact of emotional neglect/abuse, which might lead to better recognition and more adequate interventions to prevent long-term disorders. 4.3. Study strengths and limitations Some strengths as well as study limitations need to be acknowledged. Strengths of this study include: (a) a large control group to compare rates of perceived childhood adversities and negative life events; (b) a large sample of participants with a lifetime depressive and/or anxiety disorder from different recruitment settings that could be used as a built-in psychiatric control group; (c) use of a structured diagnostic interview to assess a wide range of depressive and anxiety disorders; (d) statistically controlling for comorbidity of affective disorders in examining the association of adversity with various types of affective disorders; (e) examining different forms of childhood adversity and negative life events concomitantly with statistical controls for their overlap; and (f) examining neuroticism and current affective disorder as a possible moderator variable. Some limitations of the present study also have to be acknowledged: (a) using a retrospective study design, causal interpretations of the relationships found are not warranted; (b) reliance upon retrospective reports in the assessment of childhood adversity and negative life events without objective collaboration of their occurrence; (c) assessment of childhood adversity via interview whereas negative life events across the life span were assessed via questionnaire. Because interview assessments are generally considered more reliable than checklist questionnaires this difference in assessment methodology may have resulted in a stronger association of childhood adversity versus negative life eve with affective disorders; (d) no detailed timing of negative life experiences across the life span which precluded more fine- Role of funding source The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-Mw, grant number 10-000-1002) and is supported by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Scientific Institute for Quality of Healthcare (IQ healthcare), Netherlands Institute for Health Services Research (NIVEL) and Netherlands Institute of Mental Health and Addiction (Trimbos). 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