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JAD-04525; No of Pages 10
Journal of Affective Disorders xxx (2010) xxx–xxx

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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
Institute of Psychology, Leiden University, Leiden, The Netherlands
b
Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands
c
Department of Psychiatry/EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands
d
Department of Psychiatry, University Medical Center Groningen, Groningen, The Netherlands

a r t i c l e i n f o a b s t r a c t

Article history: Background: Although several studies have shown that life adversities play an important role in
Received 5 October 2009 the etiology and maintenance of both depressive and anxiety disorders, little is known about
Received in revised form 24 February 2010 the relative specificity of several types of life adversities to different forms of depressive and
Accepted 24 February 2010
anxiety disorder and the concurrent role of neuroticism. Few studies have investigated
Available online xxxx
whether clustering of life adversities or comorbidity of psychiatric disorders critically influence
these relationships.
Keywords:
Methods: Using data from the Netherlands Study of Depression and Anxiety (NESDA), we
Anxiety
analyzed the association of childhood adversities and negative life experiences across the
Depression
Trauma lifespan with lifetime DSM-IV-based diagnoses of depression or anxiety among 2288
Life events participants with at least one affective disorder.
Neuroticism Results: Controlling for comorbidity and clustering of adversities the association of childhood
Emotional neglect 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 pervasive lifetime and current comorbidity among DSM

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: Spinhoven@FSW.LeidenUniv.NL (P. Spinhoven).
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) pro-
posed 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
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
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 investi-
gating 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 specifi-
cally, 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 dis-
orders; 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, special-
ized 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 bio-
markers. 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.
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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 con-
ducted 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 de-
scribed 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’. Psycholog-
ical 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 dichot-
omously 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
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
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 be-
tween 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” multicolli-
nearity (O'Brien, 2007). Following this, multivariate associa-
tions (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 control-
ling 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 prev-
alence 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
 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 con-
trolling 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. Partici-
pants 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 Any disorder (CIDI) Odds ratio

(n = 498) (n = 2288)

n % n %

Childhood adversity to age 16

Divorce parents 56 11.2 303 13.2 1.205
Placed in a childhome a 13 2.6 98 4.3 1.669
Placed in juvenile prison a 1 .2 8 .3 1.744
Raised in foster family a 19 3.8 78 3.4 .890
Regularly ran away from home a 11 2.2 117 5.1 2.386 ⁎⁎
Emotional neglect 94 18.9 1033 45.1 3.538 ⁎⁎⁎
Psychological abuse 56 11.2 667 29.2 3.248 ⁎⁎⁎
Physical abuse 32 6.4 368 16.1 2.791 ⁎⁎⁎
Sexual abuse 63 12.7 471 20.6 1.790 ⁎⁎⁎
LTE-Q
Seriously ill, wounded or victim of violence 167 33.5 910 39.8 1.309 ⁎⁎
Seriously ill, wounded or victim of violence of family member 350 70.3 1481 64.7 .776 ⁎
Parent, child, brother or sister died 296 59.4 1196 52.3 .747 ⁎⁎
Friend or family member died 332 66.7 1428 62.4 .830
Separation of partner 180 36.1 1200 52.4 1.949 ⁎⁎⁎
A friendship with close friend or family member ended 152 30.5 970 42.4 1.675 ⁎⁎⁎
Serious problem with close friend, family member or neighbor 102 20.5 719 31.4 1.779 ⁎⁎⁎
Became unemployed or looked for a job without result 104 20.9 653 28.5 1.513 ⁎⁎⁎
Fired from job 75 15.1 505 22.1 1.597 ⁎⁎⁎
Serious financial problems 50 10.0 509 22.2 2.564 ⁎⁎⁎
Contact with police or justice by misdemeanor 65 13.1 324 14.2 1.099
Something worthwhile or money was stolen or lost 182 36.5 741 32.4 .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 consis-
tency 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 adversi-
ties, 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,
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
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 inter-
action term (Baron and Kenny, 1986). Next, we performed a
GEE to analyze whether neuroticism moderated the relation-
ship 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 repre-
senting 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 demo-
graphic 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
 6
span to anxiety and depressive disorders, J. Affect. Disord. (2010), 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

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)

P. Spinhoven et al. / Journal of Affective Disorders xxx (2010) xxx–xxx

Variables Dysthymia Depression GAD Social phobia Panic disorder Agoraphobia Any depressive disorder Any anxiety disorder Number of disorders

ARTICLE IN PRESS
(n = 648) (n = 1887) (n = 763) (n = 892) (n = 860) (n = 281) (n = 1935) (n = 1738) (n = 2288)

Childhood adversity to age 16

Divorce parents 1.459 ⁎⁎ .998 1.215 1.006 .973 1.223 1.009 1.151 1.052
Emotional neglect 2.281 ⁎⁎⁎ 1.907 ⁎⁎⁎ 1.521 ⁎⁎⁎ 1.593 ⁎⁎⁎ 1.136 1.341 ⁎ 2.121 ⁎⁎⁎ 1.600 ⁎⁎⁎ 1.329 ⁎⁎⁎
Psychological abuse 2.111 ⁎⁎⁎ 1.938 ⁎⁎⁎ 1.476 ⁎⁎⁎ 1.412 ⁎⁎⁎ 1.210 ⁎ 1.215 2.102 ⁎⁎⁎ 1.569 ⁎⁎⁎ 1.300 ⁎⁎⁎
Physical abuse 1.962 ⁎⁎⁎ 1.615 ⁎⁎ 1.417 ⁎⁎ 1.286 ⁎ 1.377 ⁎⁎ 1.147 1.664 ⁎⁎ 1.499 ⁎⁎ 1.257 ⁎⁎⁎
Sexual abuse 2.109 ⁎⁎⁎ 1.524 ⁎⁎ 1.310 ⁎ 1.422 ⁎⁎⁎ 1.236 ⁎ 1.161 1.478 ⁎⁎ 1.489 ⁎⁎ 1.234 ⁎⁎⁎
LTE-Q
Seriously ill, wounded or victim of violence 1.528 ⁎⁎⁎ 1.358 ⁎⁎ 1.318 ⁎⁎ 1.209 ⁎ 1.144 .996 1.405 ⁎⁎ 1.171 1.143 ⁎⁎⁎
Seriously ill, wounded or victim of violence of family 1.216 1.244 1.026 1.177 1.110 1.078 1.210 1.243 ⁎ 1.096 ⁎⁎
member
Parent, child, brother or sister died 1.246 1.468 ⁎⁎ 1.154 1.044 .996 .974 1.340 ⁎ 1.103 1.098 ⁎⁎
Friend or family member died .889 1.003 .928 1.023 1.094 1.224 .918 .995 1.030
Separation of partner 1.247 ⁎ 1.227 1.210 ⁎ 1.138 1.064 .942 1.301 ⁎ 1.065 1.079 ⁎
A friendship with close friend or family member ended 1.317 ⁎⁎ 1.270 ⁎ 1.168 1.337 ⁎⁎⁎ 1.222 ⁎ .984 1.225 1.272 ⁎ 1.131 ⁎⁎⁎
Serious problem with close friend, family member or 1.366 ⁎⁎ 1.283 ⁎ 1.339 ⁎⁎ .993 1.088 1.077 1.209 1.131 1.101 ⁎⁎
neighbor
Became unemployed or looked for a job without result 1.635 ⁎⁎⁎ .971 1.289 ⁎⁎ 1.223 1.261 ⁎ .947 1.060 1.213 1.060
Fired from job 1.496 ⁎⁎⁎ 1.156 1.132 1.121 1.076 .950 1.286 1.145 1.097 ⁎
Serious financial problems 1.440 ⁎⁎⁎ 1.460 ⁎⁎ 1.202 1.135 .992 .975 1.536 ⁎⁎ 1.070 1.123 ⁎⁎⁎
Contact with police or justice by misdemeanor 1.003 .808 .994 1.204 1.214 1.081 .903 1.331 1.014
Something worthwhile or money was stolen or lost 1.268 ⁎ 1.259 .947 1.202 .991 1.170 1.315 ⁎ .845 1.027

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.
span to anxiety and depressive disorders, J. Affect. Disord. (2010), 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

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).

Lifetime disorders (CIDI)

P. Spinhoven et al. / Journal of Affective Disorders xxx (2010) xxx–xxx

ARTICLE IN PRESS
Variables 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)

Childhood adversity to age 16

Divorce parents 1.183 .766 1.039 .855 .947 1.089 .773 .918 .958
Emotional neglect 1.49*** 1.627*** 1.176 1.473*** .993 1.355 2.043*** 1.573*** 1.223***
Psychological abuse 1.196 1.260 1.091 1.087 1.045 1.095 1.534* 1.332 1.098*
Physical abuse 1.065 .970 1.005 .865 1.342 1.140 .851 .998 1.018
Sexual abuse 1.54*** 1.175 1.003 1.198 1.155 1.154 1.277 1.346* 1.122***
LTE-Q
Seriously ill, wounded or victim of violence 1.188 1.209 1.173 1.100 1.024 1.003 1.286 1.146 1.081*
Seriously ill, wounded or victim of violence of family 1.131 1.215 .957 1.165 1.112 1.139 1.307* 1.306* 1.081*
member
Parent, child, brother or sister died 1.102 1.338* 1.117 .991 .960 .932 1.298 1.096 1.067
Friend or family member died .845 .999 .935 .986 1.166 1.303 .836 .924 1.008
Separation of partner .993 1.094 1.116 1.026 .980 .934 1.146 1.004 1.023
A friendship with close friend or family member ended 1.005 1.128 .992 1.260* 1.148 1.000 1.115 1.188 1.061
Serious problem with close friend, family member or 1.059 1.057 1.23* .827 .990 1.051 1.018 .969 1.018
neighbor
Became unemployed or looked for a job without result 1.330* .739* 1.132 1.093 .893 .865 .829 1.068 .977
Fired from job 1.146 1.126 .929 .945 1.263 1.090 1.226 1.080 1.055
Serious financial problems 1.079 1.270 1.010 1.008 .992 .930 1.307 .975 1.042
Contact with police or justice by misdemeanor .819 .698* .918 1.076 1.227 1.066 .771 1.243 .947
Something worthwhile or money was stolen or lost 1.146 1.095 .845 .965 .705*** 1.030 1.071 .773* .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.

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 symptomatol-
ogy does not significantly affect adversity–disorder relation-
ships 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 disor-
der, 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 (in-
stead 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
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
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 experi-
ences during childhood in particular may contribute to vulner-
ability 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 co-
occurrence 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 wheth-
er neuroticism or current psychopathology moderate the
 ARTICLE IN PRESS
P. Spinhoven et al. / Journal of Affective Disorders xxx (2010) xxx–xxx
adversity–disorder relationships. Although including neuroti-
cism 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 neuroti-
cism 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 neuroti-
cism moderates adversity–disorder relationships and conse-
quently 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).
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-
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
9
grained analyses of context, severity and in particular temporal
order; and (e) the absence of systematic assessments for post-
traumatic 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 relation-
ships 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 work-
ers and the general public about the possible detrimental
impact of emotional abuse may help to reduce underestima-
tion of the impact of emotional neglect/abuse, which might
lead to better recognition and more adequate interventions to
prevent long-term disorders.
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).
Conflict of interest
No conflict declared.
Acknowledgements
We thank all mental health care organizations for their assistance in the
data collection and all patients for their participation in this study.
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