Accepted Manuscript

Title: Association of trauma, Posttraumatic Stress Disorder

and Conduct Disorder: a systematic review and meta-analysis

Author: Anka Bernhard Anne Martinelli Katharina

Ackermann Daniel Saure Christine M. Freitag

PII: S0149-7634(16)30341-4
DOI: http://dx.doi.org/doi:10.1016/j.neubiorev.2016.12.019
Reference: NBR 2694

To appear in:

Received date: 4-6-2016

Revised date: 28-11-2016
Accepted date: 19-12-2016

Please cite this article as: Bernhard, Anka, Martinelli, Anne, Ackermann, Katharina,
Saure, Daniel, Freitag, Christine M., Association of trauma, Posttraumatic Stress
Disorder and Conduct Disorder: a systematic review and meta-analysis.Neuroscience
and Biobehavioral Reviews http://dx.doi.org/10.1016/j.neubiorev.2016.12.019

This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.
Association of trauma, Posttraumatic Stress Disorder and Conduct Disorder: a systematic

review and meta-analysis

Bernhard, Ankaa,*, Martinelli, Annea, Ackermann, Katharinaa, Saure, Danielb, & Freitag, Christine M.a

a
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University

Hospital Frankfurt, Goethe University, Deutschordenstraße 50, 60528 Frankfurt am Main, Germany
b
Institute of Medical Biometry and Informatics (IMBI), University Hospital Heidelberg, Im

Neuenheimer Feld 130.3, 69120 Heidelberg, Germany

_________

*Corresponding author at: Department of Child and Adolescent Psychiatry, Psychosomatics and

Psychotherapy, University Hospital Frankfurt, Goethe University, Deutschordenstraße 50, 60528

Frankfurt am Main, Germany. Fax number: +496963015843. E-mail address: [email protected]

(Anka Bernhard)

1
Highlights

Studies on trauma and PTSD in CD are scarce

Individuals with CD compared to non-CD experience specific and multiple traumata
Increased lifetime PTSD prevalence was found in adults with a history of CD
Females with CD show a higher lifetime prevalence of PTSD than males with CD
Sophisticated longitudinal studies are needed to clarify specific models of comorbidity

2
Abstract

BERNHARD, A., A. Martinelli, K. Ackermann, D. Saure and C. M. Freitag. Association of trauma,

Posttraumatic Stress Disorder and Conduct Disorder: a systematic review and meta-analysis.

NEUROSCI BIOBEHAV REV XX(X) XXX-XXX. –

Objective: To summarize findings of previous studies on the prevalence of trauma and Posttraumatic

Stress Disorder (PTSD) in Conduct Disorder (CD).

Method: We conducted a systematic review and meta-analysis following the PRISMA guidelines.

Ebsco and PubMed databases were searched from January 1980 until April 2016, employing relevant

keywords.

Results: Nine studies from western industrialized countries met inclusion criteria. Data of four clinical

studies in children and adolescents was aggregated by meta-analysis, resulting in a lifetime PTSD

prevalence of 11% (95% CI: 7-17%) in CD, with higher rates in females than males. Similar

prevalence rates were observed in a population based study in adults.

Conclusions: Studies on the association of trauma, PTSD and CD are scarce. Still, an increased rate of

PTSD in CD, especially in females, was observed. The high rate of PTSD in CD may be due to shared

risk factors; furthermore, CD might increase the risk for comorbid PTSD due to CD inherent risk

taking behavior. To study pathways of risk, especially longitudinal studies are necessary.

Key Words Conduct Disorder ◦ Trauma ◦ Posttraumatic Stress Disorder ◦ Prevalence ◦ Gender

Differences ◦ Models of Comorbidity

3
Table of contents

1. Introduction ................................................................................................................................... 5
1.1. Conduct Disorder .................................................................................................................... 5
1.2. Traumatic events and PTSD .................................................................................................... 5
1.3. Gender differences .................................................................................................................. 7
1.4. Aims ........................................................................................................................................ 7
2. Methods .......................................................................................................................................... 8
2.1. Literature search ...................................................................................................................... 8
2.2. Data extraction and meta-analysis ........................................................................................... 8
3. Results............................................................................................................................................. 9
3.1. Prevalence of trauma in CD .................................................................................................... 9
3.2. Gender differences of trauma in CD ..................................................................................... 10
3.3. Prevalence of PTSD in CD .................................................................................................... 11
3.4. Gender differences of PTSD in CD ....................................................................................... 12
3.5. Chronological order of trauma, PTSD and CD ..................................................................... 13
4. Discussion ..................................................................................................................................... 14
4.1. Prevalence of trauma in CD including gender differences .................................................... 15
4.2. Prevalence of PTSD in CD including gender differences ..................................................... 16
4.3. Models of comorbidity .......................................................................................................... 17
4.3.1. Possible shared risk factors for PTSD and CD .................................................................. 17
4.3.2. Possible correlated disorder specific risk factors for PTSD and CD ................................. 20
4.3.3. One disorder as risk factor for the other disorder .............................................................. 21
4.3.4. Summary of risk factors and possible developmental pathways ....................................... 22
4.4 Conclusions ........................................................................................................................... 23

4
 1. Introduction

1.1. Conduct Disorder

Conduct Disorder (CD) refers to aggressive, anti-social and rule-breaking behavior in children

and adolescents (American Psychiatric Association, 2013). It consists of repetitive and persistent

behaviors which lead to violation of elementary rights of others and age-related societal norms.

Behavioral patterns of CD can be grouped into four areas: aggression towards people and animals,

destruction of property, deceitfulness or theft and serious violation of rules. CD is one of the most

frequent diagnosis and reasons for referral to Child and Adolescent Mental Health Services and has a

highly negative impact for the affected individuals, their families, teachers and society (Scott et al.,

2001). Persistence rates of CD are high, with 50% to 80% of boys meeting criteria for CD also three to

four years later (Lahey et al., 2002). An increased rate of antisocial personality disorder also has been

found in adulthood (Loeber et al., 2000). European and North American studies reported a prevalence

of CD of 1-3% in girls and 2-5% in boys, with rates increasing during puberty (Maughan et al., 2004).

Furthermore, over the last decades an increasing prevalence of CD has been reported in Western

industrialized countries (Collishaw et al., 2004) and especially rates for girls have increased over

recent years (Costello et al., 2006).

CD shows a high rate of psychiatric comorbid disorders and has been associated with different

psychosocial risk factors. For example, internalizing disorders such as anxiety disorders, have been

described as a common comorbidity of CD with prevalence rates varying between 13-69% (Angold et

al., 1999; Ollendick et al., 1999). Studies with delinquent adolescents indicate a high rate of

comorbidity between CD, trauma exposure and Posttraumatic Stress Disorder (PTSD; Allwood et al.,

2008; Krischer and Sevecke, 2008; Nock et al., 2007; Steiner et al., 1997). In studies in incarcerated

adolescents, up to 70% reported a history of trauma exposure, and 37-65% showed comorbid PTSD

(Cauffman et al., 1998; Dixon et al., 2005; Ruchkin et al., 2002).

1.2. Traumatic events and PTSD

According to DSM-IV-TR (American Psychiatric Association, 2000), the experience of a

traumatic event is characterized by two components: 1) an individual experienced, witnessed or was

5
confronted with one or more events which involved actual or threatened death, serious injury or a

threat to the physical integrity of self or others; and 2) the individual‘s response involved intense fear,

helplessness or horror. After trauma exposure, PTSD development is possible with symptoms of

persistent re-experiencing or avoidance of trauma-related stimuli and increased arousal for at least a

month. Reported prevalence rates of trauma and PTSD in Western industrialized countries have been

heterogeneous (Schafer et al., 2006; Tagay et al., 2013).

In different European and US-American studies, lifetime trauma prevalence in children and

adolescents varied between 23%-92% (Breslau et al., 1991; Copeland et al., 2007; Essau et al., 1999;

Lipschitz et al., 2000). In adults, also a broad range of lifetime trauma exposure with 22-90% has been

reported (Johnson et al., 2009; Perkonigg et al., 2000). Thus, the majority of the population experience

at least one traumatic event (defined according to DSM-IV TR criteria) in their life (Breslau et al.,

1998; Stein et al., 1997). Lifetime prevalence for PTSD differed between 0.5%-9% in children and

adolescents (Copeland et al., 2007; Cuffe et al., 1998; Elklit, 2002; Essau et al., 1999; Giaconia et al.,

1995), and approximately 6% of adolescents exposed to any kind of trauma subsequently fulfilled

criteria of PTSD (Essau et al., 1999). In adults, 10-20% of the trauma exposed individuals developed a

PTSD (Hidalgo and Davidson, 2000). Lifetime PTSD prevalence in population based studies in adults

ranged between 0.5-9% in Western community samples (American Psychiatric Association, 2013;

Kessler et al., 1995; Kessler et al., 2005), while in high risk populations lifetime PTSD prevalence was

considerably higher, e.g. 58% in police or fire services personal (Kessler et al., 1995).

The divergent results regarding PTSD and especially trauma prevalence may be explained by

several reasons (Resch and Brunner, 2004; Simons and Herpertz-Dahlmann, 2008): 1) Sample related

differences: Some samples were small, included pre-specified individuals, or studied prevalence of

PTSD only for specific trauma types such as the experience of a natural disaster (Foa et al., 2001). 2)

Methodological differences: contrasting methods were used to assess trauma and PTSD such as

structural diagnostic interviews or questionnaires with different raters (self-ratings, parent/teacher

reports). 3) Sometimes a clear definition of trauma was missing (Nader, 2008), especially it often

remained unclear whether both trauma-criteria according to DSM-III-R/-IV (TR) were verified.

6
1.3. Gender differences

Previous studies reported a higher trauma prevalence in boys than in girls, especially for

experiencing assaultive violence, serious injuries or accidents (Breslau et al., 2006), which is in line

with findings in adults reporting for males a much as twice higher likelihood to experience trauma

than females (Breslau et al., 1998; Stein et al., 1997). In contrast, both in children and adolescents as

well as adults, several studies reported higher PTSD prevalence with an up to twice as higher risk and

more severe and longer remaining PTSD symptoms in females than males with PTSD prevalence

ranging between 0.1-6% for males and 0.7-12% for females (Breslau et al., 1991; Dixon et al., 2005;

Copeland et al., 2007; Cuffe et al., 1998; Elklit, 2002; Giaconia et al., 1995, Kessler et al., 1995).

Besides possible underlying biological risk factors, higher PTSD prevalence in females than males has

been explained by the fact that women are more often exposed to more severe trauma such as sexual

abuse or rape (Ehlers, 2000). These so-called man-made traumata show a particularly strong

association with PTSD prevalence, duration and severity compared to non-interpersonal traumata such

as natural or technical disasters (Charuvastra and Cloitre, 2009; Kessler et al., 2005; Schepker, 1997).

Sexual assault has been reported as the strongest predictor for PTSD development (Frans et al., 2005),

with about 50% of sexually abused children, adolescents and adults developing PTSD (Giaconia et al.,

1995; Johnson et al., 2009; Kessler et al., 1995). As females experience more often man-made-

traumata such as sexual abuse and rape, they are thereby more vulnerable than males to develop PTSD

(Kerig et al., 2009; Lipschitz et al., 1999). Given these results, gender differences may also be found

studying the prevalence of trauma and PTSD in children and adolescents with CD.

1.4. Aims

In summary, CD is a common and serious psychiatric disorder in children and adolescents

with a chronic course into adulthood. A high prevalence of trauma and PTSD in delinquent

adolescents has been reported in previous studies. By this review based on a systematic literature

search and complemented by meta-analysis, we aim at studying the prevalence of trauma and PTSD in

children and adolescents with CD or in adults with a history of CD, also analyzing gender related

differences. We expect an increased prevalence of trauma and PTSD in individuals with CD compared

7
to individuals without CD and a higher PTSD prevalence in females with CD compared to males with

CD. In addition, we aim at comparing the kind of trauma observed in individuals with and without

CD, and to explore information on the longitudinal course as well as possible shared risk factors for

trauma, PTSD, and CD to fuel insight into possible models of comorbidity.

2. Methods

2.1. Literature search

The systematic literature review and meta-analysis was conducted following the PRISMA

guidelines (Moher et al., 2009). The search strategy, inclusion and exclusion criteria as well as data to

be extracted were defined in advance. A systematic literature search was conducted in the electronic

databases Ebsco (PsycInfo, PsycArticles, PsycIndex) and PubMed using the relevant terms ―trauma

and Conduct Disorder”, ―Posttraumatic Stress Disorder and Conduct Disorder”, and “PTSD and

Conduct Disorder”. The search was first done in November 2015 for studies published after January

1980, and was updated in April 2016 for the time period since November 2015 without any restriction

and filters. After duplicates were removed, all remaining articles were checked in a first (title, abstract)

and second (whole article) screening. Studies were included if they 1) sampled human participants (all

age groups); 2) reported information about the prevalence and/or comorbidity of trauma and/or PTSD

and CD according to DSM-III, DSM-III-R, DSM-IV or DSM-IV-TR criteria. Studies were excluded if

they (1) assessed conduct problems, delinquent behavior, antisocial personality disorder without

fulfilling CD diagnosis; (2) did not implement DSM-III, DSM-III-R, DSM-IV or DSM-IV-TR criteria

for trauma exposure, PTSD or CD diagnosis; (3) were intervention or single case studies or (4) used

the word ―conduct‖ without relation to CD or ―trauma‖ without relation to trauma exposure and/or

PTSD and CD (e.g. medical studies about traumatic brain injury).

2.2. Data extraction and meta-analysis

For meta-analysis, data were extracted by age, gender, population, and diagnostic methods.

Only comparable studies according to these aspects were included in the meta-analyses. Pooled

estimates of event rates with corresponding 95% confidence intervals were calculated on the base of
8
the Freeman-Tukey double arcsine transformation (Freeman and Tukey, 1950; Miller, 1978) within a

random effects model framework. Statistical heterogeneity of combined study results was assessed by

the I2 statistic. The results were visualized by forest plots of event rates. For statistical analysis the

statistical software R (The R Foundation for Statistical Computing) with the ‗meta‘ package

(Schwarzer, 2015) was used.

3. Results

By all searches 951 articles were found. After removing duplicates, remaining articles were

checked in a first (N=524 articles) and second screening (N=76 articles) for information regarding

prevalence (including gender differences) and comorbidity of trauma and/or PTSD with CD (see

Figure 1). According to the above mentioned inclusion criteria, nine cross-sectional, population based

or clinical studies in children and adolescents with CD or in adults with a history of CD were found,

all from Western industrialized societies (see Table 1). Of these (see Table 2), four studies reported

information about the prevalence of trauma and CD (two in children and adolescents, two in adults).

One study in adults also mentioned gender differences. Six studies reported information about PTSD

prevalence in CD (four in children and adolescents, two in adults), of which three studies in children

and adolescents and one study in adults reported gender differences.

3.1. Prevalence of trauma in CD

In children and adolescents, two studies reported data about the prevalence of trauma in CD,

one clinical study in girls and boys with CD aged 10-17 years, and one study on a high-risk population

of adolescents aged 12-23 years. Both studies did not include a comparison group of healthy controls.

In the clinical sample, 56% of children and adolescents with CD reported having experienced at least

one traumatic event such as physical or sexual abuse, vehicle accident, or being witness of death,

suicide or abuse of a loved one (Reebye et al., 2000). In the study on high-risk adolescents living in

residential care, 21% (95% CI: 16.0-26.3) of the children exposed to maltreatment (witness of

violence, victim of physical violence, victim of familial physical violence, victim of sexual abuse)

fulfilled CD criteria within the last three months while only 16% (95% CI: 9.5-23.7) of those without

9
maltreatment showed CD (OR [odds ratio] 2.0, p=.049; Greger et al., 2015). Especially exposure to

community violence, both as victims (OR 3.8, p<.001) and witnesses (OR 2.2, p=.018), increased the

odds for CD (Greger et al., 2015). Due to high study heterogeneity no meta-analytic aggregation of

both studies was possible (Reebye et al., 2000 & Greger et al., 2015: I²=97.2%, tau²=.07, p<.0001).

In adults, two studies reported data on the prevalence of trauma in adults with a history of CD,

a large population-based study (Afifi et al., 2011) and a study on war veterans (Koenen et al., 2002).

Of the adults in the population based study, 93% with a history of CD reported lifetime trauma

experience (such as war-related trauma, physical or sexual abuse, unexpected death of a close person

or life-threatening accident) compared to 85% without CD. Adjusted for sociodemographic variables,

adults with a lifetime diagnosis of CD were 2.7 times more likely to report having experienced a

lifetime traumatic event compared to individuals without CD (AOR [adjusted Odds Ratio for age,

marital status, income, ethnicity, education, sex] 2.7; 95% CI: 2.0-3.6, p<.001; Afifi et al., 2011).

Lifetime trauma prevalence in females with a history of CD was higher than in females without CD

(96% vs. 84%; AOR 5.1, 95% CI: 3.0-8.6, p<.001; Afifi et al., 2011). Males with CD similarly had a

higher trauma prevalence than males without CD (92% vs. 85%; AOR 2.3, 95% CI: 1.6-3.2, p<.001).

In both, males and females all types of childhood maltreatment (such as physical or sexual abuse)

were strongly associated with higher odds of lifetime CD (AOR 2.3 - 4.4 for males, 3.7 - 4.7 for

females). The strongest association of lifetime trauma for both males and females with CD was found

for assaultive violence (e.g. physically attacked, threatened with a weapon, rape; (AOR ranges of 2.7 -

4.3, range of 95% CI: 2.3 - 7.5 for males; AOR ranges 2.0 - 4.8, range of 95% CI: 1.2 - 6.6 for

females). In adult war veterans with a history of CD in childhood, 53% had experienced lifetime

trauma exposure, which was higher than in adult war veterans without history of CD (38%; OR 1.4,

95% CI: 1.3-1.5, p<.05; Koenen et al., 2002). Again, both studies were heterogeneous, so no meta-

analysis was possible (Afifi et al., 2011& Koenen et al., 2002: I²=98.8%, tau²=.01, p<.0001).

3.2. Gender differences of trauma in CD

None of the two included studies in children and adolescents reported summary lifetime

prevalence of trauma by gender. Specific trauma events were compared in the clinical study: Girls

10
with CD reported more often being victims of sexual assault than boys with CD (47% vs. 0%). In

contrast, boys with CD reported more frequently having been involved in car accidents (35% vs. 0%),

near fatal falls from a cliff, tree, or vehicle (20% vs. 7%), or physical assaults (10% vs. 0%; Reebye et

al., 2000). In the population based study on adults, females with CD had a higher overall trauma

prevalence than males (96% vs. 92%) and were 2.2 times (AOR) more likely to report trauma

experience than males with CD (95% CI: 1.3 - 4.2, p<0.01; Afifi et al., 2011). In addition, the kind of

lifetime traumata differed between females and males with a history of CD. Especially, exposure to

sexual assault or rape after the age of 18 was most strongly associated with gender (AOR 16.9 females

versus males with CD; 95% CI: 6.0-47.8, p < .001). In contrast, adult females with a history of CD

reported less frequently than males with CD having been in a life-threatening accident (AOR 0.4, 95%

CI: 0.3-0.6, p<.001), physically attacked by somebody other than their partner (AOR 0.4, 95% CI: 0.3-

0.6, p<.001), threatened with a weapon (AOR 0.5, 95% CI: 0.3 - 0.7, p<.001), or having seen a person

badly injured, killed or dead (AOR 0.6, 95% CI: 0.4-0.8, p<.001; Afifi et al., 2011).

3.3. Prevalence of PTSD in CD

Four clinical studies assessed PTSD and CD prevalence in children and adolescents. Reported

rates varied between 7 to 16% for lifetime prevalence (Burket and Myers, 1995; Connor et al., 2007;

Ilomäki et al., 2012) and 17% for current PTSD prevalence in CD (Reebye et al., 2000). No control

data were assessed. Data were aggregated by meta-analysis (see Figure 2; heterogeneity index

I²=42.9%, tau²=.003, p=.15), resulting in a lifetime PTSD prevalence in children and adolescents with

CD of 11% (32/298 individuals, 95% CI: 7-17%). Excluding the study from Reebye et al. (2000)

which reported current prevalence, an estimated PTSD prevalence of 9% (21/233 individuals, 95% CI:

5-13%) in children and adolescents with CD results. One study compared lifetime PTSD prevalence in

childhood-onset vs. adolescent-onset CD and reported a significantly higher prevalence of PTSD in

adolescent-onset CD (childhood onset 5% vs. adolescent onset 31%, p=.03; Connor et al., 2007). The

majority of adolescents with CD developed PTSD symptoms after exposition to numerous traumata

(72.3% reported two or more traumata; Ilomäki et al., 2012). A high degree of exposure to multiple

traumata in high-risk adolescents increased the odds of psychiatric disorders in general, and especially

11
for CD (OR 9.8; 95% CI: 2.1-45.4, p=.003) (Greger et al., 2015) compared to those without any

experience of trauma.

In adults with a history of CD two studies reported lifetime PTSD prevalence compared to

individuals without CD. In a population based study 11% of adults with a lifetime diagnosis of CD

met lifetime PTSD criteria which was higher than in individuals without CD (6%; AOR 2.2, 95% CI:

1.8-2.7, p<.001; Afifi et al., 2011). Both, males and females with a history of CD had a higher PTSD

prevalence than males or females without CD (males: 8% vs. 4%, AOR 2.2, 95% CI: 1.7-3.0, p < .001;

females: 20% vs. 8%, AOR 2.2, 95% CI: 1.6-2.9, p < .001). In a high risk study with war veterans

64% of individuals with a past CD met lifetime PTSD criteria which was higher than in veterans

without pre-existing CD (50%; OR 1.3, 95% CI: 1.2-1.4, p<.05) (Koenen et al., 2002). Due to

significant heterogeneity no meta-analysis on PTSD prevalence in adults with a history of CD could

be calculated (Afifi et al., 2011 & Koenen et al., 2002: I²=98.8%, tau²=.01, p<.0001).

3.4. Gender differences of PTSD in CD

Three clinical studies assessed gender differences in children and adolescents. Lifetime PTSD

prevalence showed a range of 13-27% in females with CD and of 3-7% in males with CD (Burket and

Myers, 1995; Ilomäki et al., 2012). Current PTSD prevalence was 28% in girls with CD and 10% in

boys with CD (Reebye et al., 2000). These three studies were included in a meta-analysis (see Figure

2) for an estimate of female (heterogeneity index I²=37.7%, tau²=.006, p=.20) and male (heterogeneity

index I²=14.7%, tau²=.001, p=.31) lifetime PTSD prevalence in CD. Results from meta-analysis

showed a significant gender difference in the PTSD prevalence in children and adolescents with CD

with an estimated PTSD prevalence in females with CD of 20% (18/98 individuals, 95% CI: 10-32%)

and of 5% (8/93 individuals, 95% CI: 2-10%) in males with CD (p<.01). Re-analysis of the data

excluding the study of Reebye et al. (2000) reporting current prevalence, an estimated PTSD

prevalence of 16% for females (11/73 individuals, 95% CI: 7-28%) and 4% of males (4/107

individuals, 95% CI: 1-8%) with CD resulted, which again showed a significant gender difference

(p<.01). One study also compared PTSD single symptom severity assessed by a 5-point Likert scale

(Reebye et al., 2000). The mean severity of all current PTSD symptoms was significantly higher in

12
females with CD (mean 4.06, SD 0.5) than in males with CD (mean 3.28, SD 0.55, p<.05). In adults,

lifetime PTSD prevalence in females with a history of CD also was higher than in males with a history

of CD (20% vs. 8%, OR 2.5, 95% CI: 1.7-3.8, p<.001; Afifi et al., 2011).

3.5. Chronological order of trauma, PTSD and CD

To date, no longitudinal studies assessed the chronological order of trauma, PTSD and CD,

giving insight in possible causal comorbidity models. Only a few cross-sectional studies

retrospectively reported the age of onset of first symptoms of CD and PTSD, but did not report on the

age of traumatic events separately. In boys and girls with CD the majority of participants

retrospectively reported the onset of CD symptoms to be earlier than the first PTSD symptoms

(Reebye et al., 2000). PTSD symptoms occurred approximately two years after the onset of CD in

individuals with both, current CD and PTSD. This time difference was descriptively higher for girls

(mean 2.4 years, SD 5.4) than for boys (mean 1.3 years, SD 1.3). Similar, in the population based

study, the majority of adults (72.9%) diagnosed with both CD and PTSD reported retrospectively an

earlier age of onset of CD than PTSD (Afifi et al., 2011). The mean age of onset of CD symptoms was

12.5 years, SE=0.01 (females mean 13.0 years, males mean 12.3 years, SD not reported; p<.05) while

the mean age of onset of PTSD symptoms was 28.7 years, SE=0.00 (females mean 28.9 years, males

mean 28.2 years, SD not reported; p=n.s.).

Further, three studies in adult war veterans compared several risk factors for trauma and/or

PTSD development, including pre-war CD. History of CD next to substance abuse was the most

significant risk factor for trauma exposure in the category pre-exposure psychopathology (OR 1.3,

95% CI: 1.2 - 1.4, p<.05; Koenen et al., 2002). In another study, next to psychosocial risk factors such

as lack of family and social support, childhood CD was the most significant pre-war predictor of

PTSD (R =.39, p<.001) with a significant positive correlation between levels of CD behaviors and

PTSD symptom severity (summary score of DSM-III-R PTSD symptoms rated from 1 (absent) to 3

(threshold); Dikel et al., 2005). Similarly, in a third study pre-war CD compared to non-CD was

associated with higher mean war related PTSD symptoms (Mdiff =7.4, 95% CI: 3.9-10.9, p<.001;

summary score of DSM-III-R symptoms rated by a 5-point Likert scale), controlled for possible

13
confounding factors, such as war zone stress, education, employment, age of military entry, current

mental illness or substance abuse (Dillard et al., 2007).

4. Discussion

The present systematic review aimed at studying the prevalence of trauma and/or PTSD in

children and adolescents with CD or in adults with a history of CD, considering gender related

differences. All detected studies were cross-sectional; no longitudinal studies have been published to

date. Further, for children and adolescents no case-control or population based studies were found.

Due to lack of comparability of several studies (different age groups: children and adolescents vs.

adults; different gender: including only males vs. including both sexes; studied populations: clinical

study vs. high risk population vs. population based study), meta-analysis was possible only with

regard to PTSD prevalence in children and adolescents with CD, including gender differences. Due to

the small number of studies, the presence of publication bias could not be explored by funnel plots.

Human subjects across all ages were included. This makes results harder to compare, but helps to

generate ideas for future work in this field of research. Another limitation is that due to the few

population-based studies, the reported prevalence of trauma and PTSD in CD in children and

adolescents only stems from clinical samples or high-risk populations which are not representative for

the general population. Also in this age group, no case-control studies have been performed to

compare the prevalence of trauma and/or PTSD in individuals with and without CD, or compared to

other clinical samples. Still, important information about risk-factors and comorbidities in individuals

with CD can be gained from these studies. Finally, developmental pathways between trauma, PTSD

and CD cannot be properly assessed by cross-sectional studies. Thus, this review cannot answer

questions of causality between trauma exposure and the development of PTSD and CD. However, new

research questions about the interaction of trauma exposure and CD and PTSD development can be

formulated from previous cross-sectional findings.

Despite these limitations, results of this systematic review indicate a slightly higher prevalence

of trauma exposure and a higher lifetime prevalence of PTSD in CD compared to individuals without

14
CD, with higher rates in females than in males living in Western industrialized societies. These aspects

will be discussed in more detail below, followed by an elaboration of possible models of comorbidity.

4.1. Prevalence of trauma in CD including gender differences

Only two studies in children and adolescents with CD assessed trauma prevalence, but did not

include control individuals without CD. Also, one study reported lifetime, the other three months‘

prevalence data (Greger et al., 2015; Reebye et al., 2000). As trauma prevalence varies strongly by

studied samples, diagnostic methods and trauma definition (see introduction) study results can hardly

be compared to results of previous population based studies. In addition, socioeconomic conditions

and the societal environment of the studied population likely will influence trauma prevalence. For

example, in a German population based study on individuals aged 14-24 years 18% of females and

26% of males reported having experienced at least one traumatic event at some point in their life

(Perkonigg et al., 2000), while in an US-American national comorbidity survey on a comparable group

(15-24 years) 51% of females and 61% of males reported lifetime trauma exposure (Kessler et al.,

1995). These differences might be due to diverse environmental characteristics of the studied

populations, such as a lower likelihood of natural disasters, more restrictive laws concerning carrying

weapons and lower crime rates in Germany compared to the USA (Perkonigg et al., 2000). No

population based studies in children and adolescents on trauma prevalence are available from Canada

and Norway which may be compared to the clinical samples in boys and girls with CD from these

countries (Greger et al., 2015; Reebye et al., 2000). Clearly, case-control studies are needed to

systematically examine trauma prevalence using the same methods and criteria. Here, the results from

the two studies in adults may help to give first answers to this question as they indicate a slightly

higher risk of trauma exposure in individuals with a history of CD compared to individuals without

CD (Afifi et al., 2011; Koenen et al., 2002). Still, trauma prevalence also was high (85%) in

individuals without CD in the population based study from the USA (Afifi et al., 2011). This study

also reported a slightly higher trauma prevalence in females than in males with a history of CD (Afifi

et al., 2011), which was in contrast to males and females without CD who showed exactly the same

rate of trauma exposure. Results of previous studies in males and females without a psychiatric

disorder are divergent, ranging from similar lifetime trauma rates to a higher trauma exposure in males
15
than females (Breslau et al., 2006; Breslau et al., 1998; Stein et al., 2000; Stein et al., 1997). Thus, the

increased rate of lifetime trauma exposure in adult females with a history of CD compared to males

might be specific for CD.

Furthermore, the included studies show clear differences in the amount and kind of

experienced traumata in CD compared to those without CD, again with gender specific findings.

Children, adolescents and adults with CD experienced more often multiple traumata and also more

specific trauma types such as assaultive violence, rape or exposure to community violence (Afifi et al.,

2011; Greger et al., 2015; Ilomäki et al., 2012; Reebye et al., 2000). It has been suggested that the

exposure to specific kinds of traumata may be influenced by CD related behavioral patterns. For

example, individuals with CD often have challenging social relationships and might thus be at higher

risk to experience interpersonal traumata (Afifi et al., 2011; Greger et al., 2015). Moreover, these

severe, man made traumata have been especially related to a higher risk of PTSD (Brewin et al., 2000;

Frans et al., 2005; Perkonigg et al., 2000; Charuvastra and Cloitre, 2009; Kessler et al., 2005;

Schepker, 1997). The observed gender differences in types of traumatic events were similar in

children, adolescents and adults: females with CD reported more often sexual violence and trauma in

intimate relationships, while males with CD experienced more frequently life-threatening accidents,

physical violence, witnessing the death or suicide of a loved one or trauma in distant relationships

(Afifi et al., 2011; Reebye et al., 2000).

4.2. Prevalence of PTSD in CD including gender differences

Meta-analytic aggregation of the data of four clinical samples resulted in a lifetime PTSD

prevalence of 11% (95% CI: 7-17%) in children and adolescents with CD. Although Reebye et al.

(2000) reported data on current PTSD prevalence, they found the highest rates of all respective studies

in children and adolescents with CD, indicating that lifetime PTSD prevalence might have been even

higher in his sample. Exactly the same lifetime PTSD prevalence (11%) was also observed in adults

with a history of CD (Afifi et al., 2011). In contrast to the studies on children and adolescents, control

groups were included in the studies on adults, which support the notion of increased lifetime PTSD

prevalence in CD (Afifi et al., 2011; Koenen et al., 2002). Previous population based studies in

16
Western industrialized societies found a lifetime PTSD prevalence in children and adolescents of 2%-

9% (Elklit, 2002; Essau et al., 1999; Giaconia et al., 1995). Thus, it is likely that future case-control or

population based studies in children and adolescents also will observe an increased lifetime prevalence

of PTSD in CD. Females with CD showed a particularly high lifetime prevalence of PTSD, which was

exactly comparable for children, adolescents and adults (20%; Afifi et al., 2011; Burket & Myers,

1995; Ilomäki et al., 2012; Reebye et al., 2000). Several previous studies reported a higher lifetime

PTSD prevalence in females than males (Dixon et al., 2005; Giaconia et al., 1995), which was also

observed – albeit with lower rates – in individuals without CD in the population based study in adults

(Afifi et al., 2011). Thus, female gender seems to be a specific risk factor to develop PTSD in CD. As

there has been an increasing prevalence of CD especially in girls over recent years (Costello et al.,

2006), it is important to consider that these girls may be at higher risk for trauma exposure and PTSD.

The underlying gender specific mechanisms need to be established by longitudinal studies; they may

be related to the higher rate and specific trauma types observed in females with CD (see above), but

also to genetic background, neuroendocrinological or gender specific environmental risk factors and

psychiatric comorbidities.

4.3. Models of comorbidity

Given the increased lifetime prevalence of PTSD in CD, especially in females, possible

underlying models of comorbidity need to be discussed. This may fuel the design of future cross-

sectional or longitudinal studies powered to test specific hypotheses. In general, co-occurrence of two

psychiatric disorders may be explained by chance. For PTSD and CD, this hypothesis cannot be

finally excluded by this review, because of the lack of controlled or population based studies in

children and adolescents which replicate the findings in adults. Still, findings in adults clearly indicate

a higher rate of lifetime PTSD in CD. Therefore, the following models of comorbidity of CD and

PTSD are discussed below: First, the two disorders may be alternate manifestations of the same

underlying risk factors. Second, disorder specific risk factors may be correlated, or, third, the presence

of one disorder may increase the risk for the other disorder.

4.3.1. Possible shared risk factors for PTSD and CD

17
 Shared risk factors may influence the co-occurrence of PTSD and CD. These shared risk

factors may be genetic, psychosocial or biologically based environmental risk factors. Population

based twin studies have indicated shared genetic risk factors for internalizing and externalizing

symptoms in children and adolescents (Rhee et al., 2015), which also may underlie the co-occurrence

of PTSD and CD. A study in male US-American adult twins reported a high co-variation of PTSD

with latent externalizing as well as internalizing dimensions (Wolf et al., 2010). Heritability of

aggressive behavior and conduct problems has been estimated at 50-60% (Porsch et al., 2016; Waltes

et al., 2015). PTSD showed a heritability of 30-40% (Almli et al., 2014), with a higher heritability of

around 70% in adult females in one study (Sartor et al., 2012). No twin studies on shared genetic or

environmental risk factors of PTSD and CD have been published to date, so no final conclusions with

regard to overlapping heritability of both disorders can be drawn. Molecular genetic studies have

implicated genetic variants in the serotonergic, dopaminergic, and the stress hormone systems in both

disorders (Castro-Vale et al., 2016; Gressier et al., 2013; Li et al., 2016; Waltes et al., 2015). Again, no

studies have been performed to directly study possible shared molecular genetic risk factors of both

disorders.

Some of the environmental risk factors, which also interact with the individual genetic

background, may also be shared between both disorders. Maternal smoking during pregnancy (MSP)

is a well established risk factor for female and male offspring conduct disorder problems (Gaysina et

al., 2013; Palmer et al., 2016). A recent study has also implicated MSP as a strong risk factor for

PTSD (Biederman et al., 2014). MSP has been related to high arousal and excitability as well as

lethargy and reduced attention in neonates (Barros et al., 2011), low executive attention in six-months-

old (Wiebe et al., 2014) and six-years-old children (Fitzpatrick et al., 2014). In three-years-old

children, MSP reduced motivational self-regulation and increased delay aversion, especially in boys

was observed (Wiebe et al., 2015). In ten-year-old MSP exposed children, high impulsive behavior

and low classroom engagement was reported by teachers (Fitzpatrick et al., 2014). These impairments

in motivation, executive function and behavior may predispose MSP exposed children to PTSD and

CD, likely via increased risk for CD and subsequent PTSD (see 4.3.3).

18
 Low socioeconomic status, low family income/education as well as poverty has also been

found as risk factors for both disorders (Burke et al., 2002; Davidson et al., 1991; Murray and

Farrington, 2010; Perkonigg et al., 2000). Further, for both disorders, frequent exposure to early

adverse life events has been reported. Early and chronic child maltreatment, abuse and neglect, which

are currently often summarized under ―early life stress‖ (ELS) show a strong longitudinal association

with disruptive behavior patterns related to CD (Fergusson et al., 1996; Jaffee et al., 2005; Kilpatrick

and Saunders, 1999). Childhood maltreatment has also been related to substance abuse, aggressive and

delinquent behavior in adolescence, and an increased likelihood of CD (Beeghly and Cicchetti, 1994;

Burgess et al., 1987). As the exposure to ELS also increases the risk for PTSD development (Boney-

McCoy and Finkelhor, 1995; Brewin et al., 2000; Kilpatrick et al., 2003; Meyers et al., 2015), ELS

very likely is an important shared risk factor of both, CD and PTSD.

Epigenetic studies indicate a particular responsivity of the serotonergic and the HPA-axis

system to environmental factors (Jawahar et al., 2015). In addition, the immune system also has been

shown to be involved into the long-term sequelae of ELS (Nemeroff, 2016). Epigenetic studies on CD

and aggressive behavior have observed methylation changes of serotonergic, HPA axis related and

immune system related genes in adult females and males with a history of chronic physical aggression

(Guillemin et al., 2014; Provençal et al., 2014). Also, lower glucocorticoid receptor gene (NR3C1)

methylation levels have been found in young adults with a history of CD (Heinrich et al., 2015). In

PTSD, epigenetic modification has been predominantly reported for immune system related genes,

whereas differential methylation of serotonergic and HPA axis related genes modified the risk of

subsequent PTSD development in trauma exposed individuals (Zannas et al., 2015). A possible

overlap of epigenetic mechanisms related to ELS in CD or PTSD has not yet been studied.

Biomarker, in addition to genetic and epigenetic, studies have also indicated the important role

of the HPA axis in both disorders. Reduced basal and reactive cortisol levels in children and

adolescents with CD compared to individuals without CD have been reported (Cappadocia et al.,

2009; Pajer et al., 2001; Popma et al., 2007). In a longitudinal study, maltreated children showed less

prosocial, but more disruptive and aggressive behavior, which was associated with lower morning

cortisol levels one year later (Alink et al., 2012). This hypocorticolism has also been found in
19
individuals with PTSD (Ehlert et al., 2001; Heim et al., 2000). ELS has been related to lower morning

cortisol levels in children placed into foster care before age 3 years old (Puetz et al., 2016). Reduced

cortisol reactivity was observed in internationally adopted children, when they were adopted early in

life (Gunnar et al., 2009). Other studies have reported differential alteration of basal cortisol after

different forms of ELS with hypo- and hypercortisolism observed in adolescents with a history of

ELS (Essex et al., 2011). In addition, attenuated stress response has been observed especially in

female offspring of mothers exposed to a severe environmental trauma (Yong Ping et al., 2015). The

exact role of prenatal stress exposition and child ELS exposition, their influence on HPA axis activity

during development, and the differential relation to comorbidity of CD and PTSD including sex

differences need to be investigated by future longitudinal studies.

4.3.2. Possible correlated disorder specific risk factors for PTSD and CD

Disruptive and antisocial behavior has been shown to accumulate in families, including

parents and siblings of both genders, and a familial history of antisocial and aggressive behavior has

been reported as a specific risk factor for CD in children (Burke et al., 2002; Frick et al., 1992).

Further, parental antisocial behavior is associated with poor parenting, less parental supervision, cold

parental attitude and more parental conflicts, which increase risk of antisocial behavior and CD in

offspring, but also may be related to higher trauma exposure leading to PTSD in offspring of antisocial

parents (Burke et al., 2002; Medley and Sachs-Ericsson, 2009; Murray and Farrington, 2010). A

strong association has been found for physically aggressive parental punishment and oppositional

behavior in children (Stormshak et al., 2016). Severe, extremely harsh, physically punitive and abusive

parenting behaviors have been shown as a strong risk factors for CD in children (Deater-Deckard and

Dodge, 1997; Burke et al., 2002), though most research has been done in boys. Thus, parental

antisocial behavior, which is genetically and environmentally related to offspring CD, may also

expose children to more ELS thereby increasing the likelihood of PTSD development via the above

mentioned neurobiological and G x E-pathways. In addition, parental antisocial personality disorder

also is associated with maternal smoking and alcohol consumption during pregnancy (Sengupta et al.,

2015), of which smoking has been shown to increase risk for both, CD and PTSD (see 4.3.1).

Moderate maternal alcohol consumption during pregnancy has also been related to childhood-onset
20
persistent conduct problems in 13 year old children (Murray et al., 2016), and a recent meta-analysis

has found a strong association of fetal alcohol spectrum disorder with conduct disorder (Popova et al.,

2016). The role of alcohol consumption during pregnancy on offspring PTSD has not yet been studied.

More longitudinal studies with hypothesis driven data analysis testing different possible pathways of

risk are needed to disentangle parental psychopathology, parenting style and associated factors such as

maternal smoking or alcohol consumption during pregnancy and ELS in the development of comorbid

CD and PTSD considering sex differences as well as underlying neurobiological, epigenetic and

genetic influences.

4.3.3. One disorder as risk factor for the other disorder

With regard to the hypothesis that one disorder may increase the likelihood for co-occurrence

of the other disorder, several authors suggested that CD may be a risk factor for subsequent trauma

exposure and PTSD. First findings from retrospective studies in children and adolescents as well as

adults suggest an earlier age of onset of CD than of PTSD (Afifi et al., 2011; Reebye et al., 2000).

Also, in studies on adult war veterans pre-war CD was one of the strongest risk factors for trauma

exposure and PTSD development (Dikel et al., 2005; Dillard et al., 2007; Koenen et al., 2002).

Though these findings may be influenced by recall-bias, no studies have been found reporting PTSD

as a risk factor for CD or reporting PTSD onset prior to CD. This is in line with other studies

indicating a higher risk of exposure to adverse life events following CD onset (Breslau et al., 2006).

Because of the associated aggressive, risky, careless, and delinquent behavior in individuals

with CD, they may be more vulnerable to engage in severe and man-made traumatic situations and

thus at high risk to develop PTSD (Afifi et al., 2011; Breslau et al., 2006; Connor et al., 2007; Fu et

al., 2007; Greger et al., 2015; Ilomäki et al., 2012; Koenen et al., 2005; Reebye et al., 2000).

Especially individuals with CD and high callous-unemotional traits have been characterized by risk-

taking and fearless behavior (Frick and Dickens, 2006; Viding, 2012), which may make them more

vulnerable for trauma experience and PTSD development. The positive association of PTSD and CD

may also be mediated by CD associated increased aggression, hostility, and attenuated arousal in

individuals exposed to MSP or ELS. Decreased arousal levels have been related to high antisocial

21
behavior, suggesting that individuals with low arousal show more delinquent, violent and antisocial

behavior as they do not fear negative consequences of their actions (Raine, 1993). Further, individuals

with decreased arousal might seek more stimulating activities and show more antisocial and risky

behavior to increase their arousal up to an optimal level („sensation- seeking- theory―; Zuckerman,

1979). As a consequence, impulsivity, sensation seeking and risk-taking behavior in individuals with

CD could expose them to further, multiple and perhaps even more severe trauma, thereby increasing

the likelihood of PTSD in later life (Afifi et al., 2011; Ilomäki et al., 2012). In addition, when feeling

threatened, individuals with CD are more likely to act-out or to become angry or oppositional,

characteristics that could make them more vulnerable to experience traumata and subsequent PTSD

(Koenen et al., 2002). In line with this reasoning, it has been shown that peri- or posttraumatic factors

such as trauma severity, lack of social support and additional life events have a higher impact on

PTSD development than pre-traumatic factors such as low education, young age, female gender or a

history of psychiatric disorders (Brewin et al., 2000). Especially cognitive, emotional and

physiological reactions during trauma exposure seem to be relevant for PTSD development (Ehlers et

al., 1998). As CD has been related to cognitive deficits, limited emotion regulation and an impaired

ability to cope with the stress, these characteristics also may predispose individuals with CD to PTSD

(Koenen et al., 2002).

4.3.4. Summary of risk factors and possible developmental pathways

Taken all these findings together, combined developmental risk pathways are suggested for

individuals with comorbid CD and PTSD (see Figure 3): CD associated severity and kind of trauma

exposure (man made; gender specific) seem to be directly related to PTSD onset. Genetic and prenatal

biological environmental risk factors, such as MSP, and ELS induce a strong vulnerability for CD and

PTSD development, mediated by lasting changes of HPA-axis, epigenetic mechanisms and other

neurobiological, cognitive and emotional sequelae. The experience of severe traumata with subsequent

PTSD onset may be mediated by pre-existing CD and its related behavioral patterns such as risk-

taking, carelessness and sensation seeking. In addition, CD individuals may be more likely to develop

PTSD due to impaired emotion regulation, cognitive deficits and altered cortisol release in stress

situations. Still, the exact mechanisms and longitudinal pathways of CD and PTSD comorbidity need
22
to be studied by additional longitudinal studies with sophisticated designs to disentangle shared,

correlated disorder specific and disorder induced risk factors in males and females, as well as studying

underlying bio-behavioral mechanisms.

4.4 Conclusions

This work is unique as it is the first systematic review complemented by meta-analyses on the

prevalence of trauma and PTSD in CD. Results indicate an increased rate of lifetime trauma exposure

in adult females compared to males with a history of CD, the exposure to multiple, disorder and

gender specific traumata in CD, and an increased lifetime PTSD prevalence in CD, particularly in

female children, adolescents and adults. Additional, population based, clinical case-control and

longitudinal studies especially in children and adolescents are strongly needed to replicate prevalence

findings and reported risk factors as basis for the development of targeted hypotheses on bio-

behavioral etiological mechanisms.

Conflicts of interest

All authors declare no competing interests.

Financial support

This research was supported by the EU, FP7 grant no. 602407 (FemNAT-CD).

23
References

Adam, B.S., Everett, B.L., O‘Neal, E., 1992. PTSD in physically and sexually abused psychiatrically
hospitalized children. Child Psychiatry Hum. Dev. 23, 3–8. doi:10.1007/BF00706695
Afifi, T.O., Boman, J., Fleisher, W., Sareen, J., 2009. The relationship between child abuse, parental
divorce, and lifetime mental disorders and suicidality in a nationally representative adult sample.
Child Abus. Negl. 33, 139–147. doi:10.1016/j.chiabu.2008.12.009
Afifi, T.O., Brownridge, D. a, Cox, B.J., Sareen, J., 2006. Physical punishment, childhood abuse and
psychiatric disorders. Child Abuse Negl. 30, 1093–103. doi:10.1016/j.chiabu.2006.04.006
Afifi, T.O., McMillan, K.A., Asmundson, G.J.G., Pietrzak, R.H., Sareen, J., 2011. An examination of
the relation between conduct disorder, childhood and adulthood traumatic events, and
posttraumatic stress disorder in a nationally representative sample. J. Psychiatr. Res. 45, 1564–
1572. doi:10.1016/j.jpsychires.2011.08.005
Alink, L.R.A., Cicchetti, D., Jungmeen, K., Rogosch, F.A., 2012. Longitudinal Associations among
Child Maltreatment, Social Functioning, and Cortisol Regulation. Dev. Psychol. 48, 224–236.
Allwood, M.A., Dyl, J., Hunt, J.I., Spirito, A., 2008. Comorbidity and service utlization among
psychiatrically hospitalized adolescents with posttraumatic stress disorder. J. Psychol. Trauma 7,
104–21.
Almli, L.M., Fani, N., Smith, A.K., Ressler, K.J., 2014. Genetic approaches to understanding post-
traumatic stress disorder. Int. J. Neuropsychopharmacol. 17, 355–70.
doi:10.1017/S1461145713001090
American Psychiatric Association, 2013. Diagnostic and Statistical Manual of Mental Disorders, Fifth
edit. ed. Arlington, VA.
American Psychiatric Association, 2000. Diagnostic criteria from DSM-IV-TR, American P. ed.
Washington, D.C.
Angold, A., Costello, E.J., Erkanli, A., 1999. Comorbidity. J. Child Psychol. Psychiatry 40, 57–87.
Angold, A., Prendergast, M., Cox, A., Harrington, R., Simonoff, E., Rutter, M., 1995. The Child and
Adolescent Psychiatric Assessment (CAPA). Psychol. Med. 25, 739–753.
Barros, M.C.M., Mitsuhiro, S.S., Chalem, E., Laranjeira, R.R., Guinsburg, R., 2011. Prenatal tobacco
exposure is related to neurobehavioral modifications in infants of adolescent mothers. Clinics 66,
1597–603. doi:10.1590/S1807-59322011000900016
Beeghly, M., Cicchetti, D., 1994. Child maltreatment, attachment, and the self system: emergence of
an internal state lexicon in toddlers at high social risk. Dev. Psychopathol. 6, 5–30.
Biederman, J., Petty, C., Spencer, T.J., Woodworth, K.Y., Bhide, P., Zhu, J., Faraone, S. V, 2014. Is
ADHD a risk for posttraumatic stress disorder (PTSD)? Results from a large longitudinal study
of referred children with and without ADHD. World J. Biol. Psychiatry 15, 49–55.
doi:10.3109/15622975.2012.756585
Boney-McCoy, S., Finkelhor, D., 1995. Prior victimization: A risk factor for child sexual abuse and
for PTSD-related symptomatology among sexually abused youth. Child Abus. Negl. 19, 1401–
1421. doi:10.1016/0145-2134(95)00104-9
Breslau, N., Davis, C.G., Andeski, P., Peterson, E., 1991. Traumatic events and posttraumatic stress
disorder in an urban population of young adults. Arch. Gen. Psychiatry 48, 216–222.
Breslau, N., Kessler, R.C., Chilcoat, H.D., Schultz, L.R., Davis, G.C., Andreski, P., 1998. Trauma and
Posttraumatic Stress Disorder in the Community 55, 626–632.
Breslau, N., Lucia, V.C., Alvarado, G.F., 2006. Intelligence and Other Predisposing Factors in
Exposure to Trauma and Posttraumatic Stress Disorder. Arch. Gen. Psychiatry 63, 1238–1245.
Brewin, C.R., Andrews, B., Valentine, J.D., 2000. Meta-analysis of risk factors for posttraumatic
stress disorder in trauma-exposed adults. J. Consult. Clin. Psychol. 68, 748–766.
doi:10.1037/0022-006X.68.5.748
Brunner, R., Plener, P.L., Resch, F., 2012. Posttraumatische Belastungsstörung, Anpassungsstörungen
und Selbstschädigungserkrankungen., in: Fegert, J.M., Eggers, C., Resch, F. (Eds.), Psychiatrie
Und Psychotherapie Des Kindes- Und Jugendalters. Springer, Berlin, Heidelberg, pp. 598–616.
Burgess, A.W., Hartman, C.R., Mccormack, A., Ph, D., Gaccione, P., Powers, P., 1987. Antecedents
Deviant. Am. J. Psychiatry 144, 1431–1436.
Burke, J.D., Loeber, R., Birmaher, B., 2002. Oppositional Defiant Disorder and Conduct Disorder: A

24
 Review of the Past 10 Years, Part II. J. Am. Acad. Child 41, 1275–1293. doi:10.1097/00004583-
200211000-00009
Burket, R.C., Myers, W.C., 1995. Axis I and personality comorbidity in adolescents with conduct
disorder. Bull. Am. Acad. Psychiatry Law 23, 73–82.
Cappadocia, M.C., Desrocher, M., Pepler, D., Schroeder, J.H., 2009. Contextualizing the neurobiology
of conduct disorder in an emotion dysregulation framework. Clin. Psychol. Rev. 29, 506–518.
doi:10.1016/j.cpr.2009.06.001
Castro-Vale, I., van Rossum, E.F.C., Machado, J.C., Mota-Cardoso, R., Carvalho, D., 2016. Genetics
of glucocorticoid regulation and posttraumatic stress disorder — What do we know ? Neurosci.
Biobehav. Rev. 63, 143–157. doi:10.1016/j.neubiorev.2016.02.005
Cauffman, E., Feldman, S.S., Waterman, J., Steiner, H., 1998. Posttraumatic stress disorder among
female juvenile offenders. J. Am. Acad. Child Adolesc. Psychiatry 37, 1209–1216.
doi:10.1097/00004583-199811000-00022
Charuvastra, A., Cloitre, M., 2009. Social Bonds and Posttraumatic Stress Disorder. Annu. Rev.
Psychol. 59, 301–328. doi:10.1146/annurev.psych.58.110405.085650.Social
Collishaw, S., Maughan, B., Goodman, R., Pickles, A., 2004. Time trends in adolescent mental health.
J. Child Psychol. Psychiatry Allied Discip. 45, 1350–1362. doi:10.1111/j.1469-
7610.2004.00335.x
Connor, D.F., Ford, J.D., Albert, D.B., Doerfler, L.A., 2007. Conduct disorder subtype and
comorbidity. Ann. Clin. Psychiatry 19, 161–168. doi:10.1080/10401230701465269
Copeland, W.E., Keeler, G., Angold, A., Costello, E.J., 2007. Traumatic events and posttraumatic
stress in childhood. Arch. Gen. Psychiatry 64, 577–584. doi:10.1016/S0084-3970(08)79296-X
Costello, E.J., Foley, D.L., Angold, A., 2006. 10-year research update review: the epidemiology of
child and adolescent psychiatric disorders: II. Developmental epidemiology. J. Am. Acad. Child
Adolesc. Psychiatry 45, 8–25. doi:10.1097/01.chi.0000184929.41423.c0
Cuffe, S.P., Addy, C.L., Garrison, C.Z., Waller, J.L., Jackson, K.L., McKeown, R.E., Chilappagari, S.,
1998. Prevalence of PTSD in a community sample of older adolescents. J. Am. Acad. Child
Adolesc. Psychiatry 37, 147–54. doi:10.1097/00004583-199802000-00006
Davidson, J.R.T., Hughes, D., Blazer, D.G., George, L.K., 1991. Post-traumatic stress disorder in the
community: an epidemiological study. Psychol. Med. 21, 713–721.
Deater-Deckard, K., Dodge, K.A., 1997. Externalizing Behavior Problems and Discipline Revisited:
Nonlinear Effects and Variation by Culture, Context , and Gender Externalizing Behavior
Problems and Discipline Revisited : Nonlinear Effects and Variation by Culture, Context, and
Gender. Psychol. Inq. 8, 161–175. doi:10.1207/s15327965pli0803
Dikel, T.N., Engdahl, B., Eberly, R., 2005. PTSD in former prisoners of war: Prewar, wartime, and
postwar factors. J. Trauma. Stress 18, 69–77. doi:10.1002/jts.20002
Dillard, D., Jacobsen, C., Ramsey, S., Manson, S., 2007. Conduct Disorder, War Zone Stress, and
War-Related Posttraumatic Stress Disorder Symptoms in American Indian Vietnam Veterans. J.
Trauma. Stress 20, 53–62. doi:10.1002/jts.
Dixon, A., Howie, P., Starling, J., 2005. Trauma exposure, posttraumatic stress, and psychiatric
comorbidity in female juvenile offenders. J. Am. Acad. Child Adolesc. Psychiatry 44, 798–806.
doi:10.1097/01.chi.0000164590.48318.9c
Ehlers, A., 2000. Posttraumatische Belastungsstörungen. Hogrefe, Göttingen.
Ehlers, A., Clark, D.M., Dumore, E., Jaycox, L., Meadows, E., Foa, E.B., 1998. Predicting response to
exposure treatment in PTSD: The role of mental defeat and alienation. J. Trauma. Stress 11, 457–
471. doi:10.1023/A
Ehlert, U., Gaab, J., Heinrichs, M., 2001. Psychoneuroendocrinological contributions to the etiology of
depression, posttraumatic stress disorder, and stress-related bodily disorders: the role of the
hypothalamus – pituitary – adrenal axis. Biol. Psychol. 57, 141–152.
Elklit, A., 2002. Victimization and PTSD in a Danish national youth probability sample. J. Am. Acad.
Child Adolesc. Psychiatry 41, 174–81. doi:10.1097/00004583-200202000-00011
Essau, C.A., Conradt, J., Petermann, F., 1999. Häufigkeit der Posttraumatischen Belastungsstörung bei
Jugendlichen: Ergebnisse der Bremer Jugendstudie. Zeitschrift für Kinder-und
Jugendpsyschiatrie und Psychother. 27, 37–45.
Essex, M.J., Shirtcliff, E.A., Burk, L.R., Ruttle, P.L., Klein, M.H., Slattery, M.J., Kalin, N.H.,
Armstrong, J.M., 2011. Influence of early life stress on later hypothalamic-pituitary-adrenal axis
25
 functioning and its covariation with mental health symptoms: A study of the allostatic process
from childhood into adolescence the allostatic process from childhood into adolescen. Dev.
Psychopathol. 23, 1039–1058. doi:10.1126/scisignal.2001449.Engineering
Fergusson, D.M., Horwood, L.J., Lynskey, M.T., 1996. Childhood sexual abuse and psychiatric
disorder in young adulthood: II. Psychiatric outcomes of childhood sexual abuse. J. Am. Acad.
Child Adolesc. Psychiatry 35, 1365–74. doi:10.1097/00004583-199610000-00024
Fitzpatrick, C., Barnett, T.A., Pagani, L.S., 2014. Parental bad habits breed bad behaviors in youth:
Exposure to gestational smoke and child impulsivity. Int. J. Psychophysiol. 93, 17–21.
doi:10.1016/j.ijpsycho.2012.11.006
Foa, E.B., Johnson, K.M., Feeny, N.C., Treadwell, K.R.H., 2001. The Child PTSD Symptom Scale: A
preliminary examination of its psychometric properties. J. Clin. Child Psychol. 30, 376–384.
Frans, Ö., Rimmö, P.A., Aberg, L., Fredrikson, M., 2005. Trauma exposure and post-traumatic stress
disorder in the general population. Acta Psychiatr. Scand. 111, 290–291. doi:10.1111/j.1600-
0447.2004.00463.x
Freeman, M.F., Tukey, J.W., 1950. Transformations Related to the Angular and the Square Root. Ann.
Math. Stat. 21, 607–611.
Frick, P.J., Dickens, C., 2006. Current perspectives on Conduct Disorder. Curr. Psychiatry Rep. 8, 59–
72. doi:10.1007/s11920-006-0082-3
Frick, P.J., Lahey, B.B., Loeber, R., Stouthamer-Loeber, M., Christ, M.A.G., Hanson, K., 1992.
Familial risk factors to oppositional defiant disorder and conduct disorder: Parental
psychopathology and maternal parenting. J. Consult. Clin. Psychol. 60, 49–55.
doi:10.1037/0022-006X.60.1.49
Fries, E., Hesse, J., Hellhammer, J., Hellhammer, D.H., 2005. A new view on hypocortisolism.
Psychoneur 30, 1010–1016. doi:10.1016/j.psyneuen.2005.04.006
Fu, Q., Koenen, K.C., Miller, M.W., Heath, A.C., Bucholz, K.K., Lyons, M.J., Eisen, S.A., True,
W.R., Goldberg, J., Tsuang, M.T., 2007. Differential Etiology of Posttraumatic Stress Disorder
with Conduct Disorder and Major Depression in Male Veterans. Biol. Psychiatry 62, 1088–1094.
doi:10.1016/j.biopsych.2007.04.036
Gaysina, D., Fergusson, D.M., Leve, L.D., Horwood, J., Reiss, D., Shaw, D.S., Elam, K.K., Natsuaki,
M.N., Neiderhiser, J.M., Harold, G.T., 2013. Maternal smoking during pregnancy and offspring
conduct problems: evidence from 3 independent genetically sensitive research designs. JAMA
psychiatry 70, 956–63. doi:10.1001/jamapsychiatry.2013.127
Giaconia, R.M., Reinherz, H.Z., Silverman, A.B., Pakiz, B., Frost, A.K., Cohen, E., 1995. Traumas
and posttraumatic stress disorder in a community population of older adolescents. J. Am.
Acadamic Child Adolesc. Psychiatry 34, 1369–1380. doi:10.1097/00004583-199510000-00023
Green, B.L., Korol, M., Grace, M.C., Vary, M.G., Gleser, L., Smitson-Cohen, 1991. Children and
disaster: age, gender, and parental effects on PTSD syndrome. J. Am. Acadamic Child Adolesc.
Psychiatry 30, 946–51.
Greger, H.K., Myhre, A.K., Lydersen, S., Jozefiak, T., 2015. Previous maltreatment and present
mental health in a high-risk adolescent population. Child Abus. Negl. 45, 122–134.
doi:10.1016/j.chiabu.2015.05.003
Gressier, F., Calati, R., Balestri, M., Marsano, A., Alberti, S., Antypa, N., Serretti, A., 2013. The 5-
HTTLPR Polymorphism and Posttraumatic Stress Disorder : A Meta-Analysis. J. Trauma. Stress
26, 645–653. doi:10.1002/jts.
Guillemin, C., Provençal, N., Suderman, M., Côté, S.M., Vitaro, F., Hallett, M., Tremblay, R.E., Szyf,
M., 2014. DNA methylation signature of childhood chronic physical aggression in T cells of both
men and women. PLoS One 9, 1–16. doi:10.1371/journal.pone.0086822
Gunnar, M.R., Frenn, K., Wewerka, S.S., Ryzin, M.J. Van, 2009. Moderate versus severe early life
stress: Associations with stress reactivity and regulation in 10–12-year-old children.
Psychoneuroendocrinology 34, 62–75. doi:10.1016/j.psyneuen.2008.08.013.Moderate
Heim, C., Ehlert, U., Hellhammer, D.H., 2000. The potential role of hypocortisolism in the
pathophysiology of stress-relatd boldily disorders. Psychoneuroendocrinology 25, 1–35.
Heinrich, A., Buchmann, A.F., Zohsel, K., Dukal, H., Frank, J., Treutlein, J., Nieratschker, V., Witt,
S.H., Brandeis, D., Schmidt, M.H., Esser, G., Banaschewski, T., Laucht, M., Rietschel, M., 2015.
Alterations of Glucocorticoid Receptor Gene Methylation in Externalizing Disorders During
Childhood and Adolescence. Behav. Genet. 45, 529–536. doi:10.1007/s10519-015-9721-y
26
Herjanic, B., Campbell, W., 1977. Differentiating psychiatrically disturbed children on the basis of a
structured interview. J. Abnorm. Child Psychol. 5, 127–34.
Hidalgo, R.B., Davidson, J.R.T., 2000. Posttraumatic Stress Disorder: epidemiology and health-related
considerations. J. Clin. Psychiatry 61, 5–13.
Ilomäki, E., Hakko, H., Ilomäki, R., Räsänen, P., STUDY-70 workgroup, 2012. Gender differences in
comorbidity of conduct disorder among adolescents in Northern Finland. Int. J. Circumpolar
Health 71, 1–8. doi:10.3402/ijch.v71i0.17393
Jaffee, S.R., Caspi, A., Moffitt, T.E., Dodge, K.A., Rutter, M., Taylor, A., Tully, L.A., 2005. Nature ϫ
nurture : Genetic vulnerabilities interact with physical maltreatment to promote conduct
problems. Dev. Psychopathol. 17, 67–84.
Jawahar, M.C., Murgatroyd, C., Harrison, E.L., Baune, B.T., 2015. Epigenetic alterations following
early postnatal stress : a review on novel aetiological mechanisms of common psychiatric
disorders. Clin. Epigenetics 7, 1–13. doi:10.1186/s13148-015-0156-3
Johnson, J., Maxwell, A.R., Galea, S., 2009. The epidemiology of post-traumatic stress disorder.
Psychiatr. Ann. 39.
Kaufman, J., Birmaher, B., Brent, D., Rao, U., Flynn, C., Moreci, P., Williamson, D., Ryan, N.D.,
1997. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and
Lifetime Version (K-SADS-PL): initial reliability and validity data. J. Am. Acad. Child Adolesc.
Psychiatry 36, 980–988. doi:10.1097/00004583-199707000-00021
Keane, T.M., Cadell, J.M., Taylor, K.L., 1994. Mississippi Scale for Combat-Related Posttraumatic
Stress Disorder: Three Studies in Reliability and Validity. J. Consult. Clin. Psychol. 56, 85–90.
Kerig, P.K., Ward, R.M., Vanderzee, K.L., Moeddel, M.A., 2009. Posttraumatic stress as a mediator
of the relationship between trauma and mental health problems among juvenile delinquents. J.
Youth Adolesc. 38, 1214–1225. doi:10.1007/s10964-008-9332-5
Kessler, R.C., Berglund, P., Demler, O., Jin, R., Merikangas, K.R., Walters, E.E., 2005. Lifetime
Prevalence and Age-of-Onset Distributions of. Arch Gen Psychiatry 62, 593–602.
doi:10.1001/archpsyc.62.6.593
Kessler, R.C., McGonagle, K.A., Zhao, S., Nelson, C.B., Hughes, M., Eshleman, S., Wittchen, H.U.,
Kendler, K.S., 1994. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in
the United States. Results from the National Comorbidity Survey. Arch. Gen. Psychiatry.
doi:10.1001/archpsyc.1994.03950010008002
Kessler, R.C., Merikangas, K.R., 2004. The National Comorbidity Survey Replication (NCS-R):
background and aims. Int. J. Methods Psychiatr. Res. 13, 60–8.
Kessler, R.C., Sonnega, A., Bromet, E., Hughes, M., Nelson, C.B., 1995. Posttraumatic Stress
Disorder in The National Comorbidity Survey. Arch. Gen. Psychiatry 52, 1048–1060.
Kilpatrick, D.G., Ruggiero, K.J., Acierno, R., Saunders, B.E., Resnick, H.S., Best, C.L., Resnick, H.S.,
Best, C.L., Victims, N.C., 2003. Violence and Risk of PTSD , Major Depression , Substance
Abuse / Dependence , and Comorbidity : Results From the National Survey of Adolescents. J.
Consult. Clin. Psychol. 71, 692–700. doi:10.1037/0022-006X.71.4.692
Kilpatrick, D.G., Saunders, B.E., 1999. Prevalence and consequences of child victimization: results
from the national survey of adolescents.
Koenen, K.C., Fu, Q.J., Lyons, M.J., Toomey, R., Goldberg, J., Eisen, S.A., True, W., Tsuang, M.,
2005. Juvenile conduct disorder as a risk factor for trauma exposure and posttraumatic stress
disorder. J. Trauma. Stress 18, 23–32. doi:10.1002/jts.20010
Koenen, K.C., Harley, R., Lyons, M.J., 2002. A Twin Registry Study of Familial and Individual Risk
Factors for Trauma Exposure and Posttraumatic Stress Disorder. J. Nerv. Ment. Dis. 190, 209–
218. doi:10.1097/01.NMD.0000012868.95340.32
Krischer, M.K., Sevecke, K., 2008. Early traumatization and psychopathy in female and male juvenile
offenders. Int. J. Law Psychiatry 31, 253–262. doi:10.1016/j.ijlp.2008.04.008
Lahey, B.B., Loeber, R., Burke, J., Rathouz, P.J., McBurnett, K., 2002. Waxing and waning in
concert: Dynamic comorbidity of conduct disorder with other disruptive and emotional problems
over 17 years among clinic-referred boys. J. Abnorm. Psychol. 111, 556–567. doi:10.1037//0021-
843X.111.4.556
Li, L., Bao, Y., He, S., Wang, G., Guan, Y., Ma, D., Wang, P., Huan, X., Tao, S., Zhang, D., Liu, Q.,
Wang, Y., Yang, J., 2016. The Association Between Genetic Variants in the Dopaminergic
System and Posttraumatic Stress Disorder. Medicine (Baltimore). 95, 1–10.
27
 doi:10.1097/MD.0000000000003074
Lipschitz, D.S., Rasmusson, a M., Anyan, W., Cromwell, P., Southwick, S.M., 2000. Clinical and
functional correlates of posttraumatic stress disorder in urban adolescent girls at a primary care
clinic. J. Am. Acad. Child Adolesc. Psychiatry 39, 1104–1111. doi:10.1097/00004583-
200009000-00009
Lipschitz, D.S., Winegar, R.K., Hartnick, E., Foote, B., Southwick, S.M., 1999. Posttraumatic stress
disorder in hospitalized adolescents: psychiatric comorbidity and clinical correlates. J. Am.
Acad. Child Adolesc. Psychiatry 38, 385–392. doi:10.1097/00004583-199904000-00010
Loeber, R., Green, S.M., Lahey, B.B., Frick, P.J., Mcburnett, K., 2000. Findings on Disruptive
Behavior Disorders from the First Decade of the Developmental Trends Study. Clin. Child Fam.
Psychol. Rev. 3, 37–60.
Lonigan, C.J., Shannon, M.P., Taylor, C.M., Finch, A.J., Sallee, F.R., 1994. Children exposed to
Disaster: II. Risk Factors for the Development of Post-Traumatic Symptomatology. Am. Acad.
Child Adolsecent Psychiatry 33, 94–105.
Maughan, B., Rowe, R., Messer, J., Goodman, R., Meltzer, H., 2004. Conduct Disorder and
Oppositional Defiant Disorder in a national sample: Developmental epidemology. J. Child
Psychol. Psychiatry 45, 609–621.
Medley, A., Sachs-Ericsson, N., 2009. Predictors of parental physical abuse: The contribution of
internalizing and externalizing disorders and childhood experiences of abuse. J. Affect. Disord.
113, 244–254. doi:10.1016/j.jad.2008.05.020.Predictors
Meyers, J.L., Lowe, S.R., Eaton, N.R., Krueger, R., Bridget, F., Hasin, D., Brook, S., 2015. of
psychopathology : A test of stress sensitization 337–345.
doi:10.1016/j.jpsychires.2015.05.005.Childhood
Miller, J.J., 1978. The Inverse of the Freeman-Tukey Double Arcsine Transformation. Am. Stat. 32,
138.
Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., The Prisma Group, 2009. Preferred Reporting
Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement (Reprinted from
Annals of Internal Medicine). Phys. Ther. 89, 873–880. doi:10.1371/journal.pmed.1000097
Murray, J., Burgess, S., Zuccolo, L., Hickman, M., Gray, R., Lewis, S.J., 2016. Moderate alcohol
drinking in pregnancy increases risk for children‘s persistent conduct problems: Causal effects in
a Mendelian randomisation study. J. Child Psychol. Psychiatry Allied Discip. 57, 575–584.
doi:10.1111/jcpp.12486
Murray, J., Farrington, D.P., 2010. Risk Factors for Conduct Disorder and Delinquence: Key Findings
From Longitudinal Studies. Can. J. Psychiatry 55, 633–642.
Nader, K., 2008. Understanding and assessing trauma in children and adolescents. Routledge, New
York.
Nemeroff, C.B., 2016. Paradise Lost: The Neurobiological and Clinical Consequences of Child Abuse
and Neglect. Neuron 89, 892–909. doi:10.1016/j.neuron.2016.01.019
Nock, M.K., Kazdin, A.E., Hiripi, E., Kessler, R.C., 2007. Prevalence, Subtypes, and Correlates of
DSM-IV Conduct Disorder in the National Comorbidity Survey Replication. Psychol. Med. 36,
699–710.
Ollendick, T.H., Seligman, L.D., Butcher, A.T., M.div., 1999. Does anxiety mitigate the behavioral
expression of severe conduct disorder in delinquent youths? J. Anxiety Disord. 13, 565–574.
doi:10.1016/S0887-6185(99)00023-7
Orvaschel, H., 1995. Schedule for Affective Disorders and Schizophrenia for School-age Children.
Epidemiologic version-5. Center for Psychological Studies. Nova Southeastern University, Fort
Lauderdale, Florida.
Pajer, K., Gardner, W., Rubin, R.T., Perel, J., Neal, S., 2001. Decreased cortisol levels in adolescent
girls with conduct disorder. Arch. Gen. Psychiatry 58, 297–302. doi:10.1001/archpsyc.58.3.297
Palmer, R.H.C., Bidwell, L.C., Heath, A.C., Brick, L.A., Madden, P.A.F., Knopik, V.S., 2016. Effects
of Maternal Smoking during Pregnancy on Offspring Externalizing Problems: Contextual Effects
in a Sample of Female Twins. Behav. Genet. 46, 1–13. doi:10.1007/s10519-016-9779-1
Perkonigg, A., Kessler, R.C., Storz, S., Wittchen, H.U., 2000. Traumatic events and post-traumatic
stress disorder in the community: prevalence, risk factors and comorbidity. Acta Psychiatr.
Scand. 101, 46–59.
Popma, A., Doreleijers, T.A.H., Jansen, L.M.C., Goozen, S.H.M. Van, Engeland, H. Van, Vermeiren,
28
 R., 2007. The Diurnal Cortisol Cycle in Delinquent Male Adolescents and Normal Controls.
Neuropsychopharmacology 32, 1622–1628. doi:10.1038/sj.npp.1301289
Popova, S., Lange, S., Shield, K., Mihic, A., Chudley, A.E., Mukherjee, R.A.S., Bekmuradov, D.,
Rehm, J., 2016. Comorbidity of fetal alcohol spectrum disorder: A systematic review and meta-
analysis. Lancet 387, 978–987. doi:10.1016/S0140-6736(15)01345-8
Porsch, R.M., Middeldorp, C.M., Cherny, S.S., Krapohl, E., van Beijsterveldt, C.E.M., Loukola, A.,
Korhonen, T., Pulkkinen, L., Corley, R., Rhee, S., Kaprio, J., Rose, R.R., Hewitt, J.K., Sham, P.,
Plomin, R., Boomsma, D.I., Bartels, M., 2016. Longitudinal heritability of childhood aggression.
Am. J. Med. Genet. Part B Neuropsychiatr. Genet. 1–11. doi:10.1002/ajmg.b.32420
Provençal, N., Suderman, M.J., Guillemin, C., Vitaro, F., Côté, S.M., Hallett, M., Tremblay, R.E.,
Szyf, M., 2014. Association of childhood chronic physical aggression with a DNA methylation
signature in adult human T cells. PLoS One 9, 12–14. doi:10.1371/journal.pone.0089839
Puetz, V.B., Zweerings, J., Dahmen, B., Ruf, C., Scharke, W., Herpertz-Dahlmann, B., Konrad, K.,
2016. Multidimensional assessment of neuroendocrine and psychopathological profiles in
maltreated youth. J. Neural Transm. 1–12. doi:10.1007/s00702-016-1509-6
Pynoos, R., Steinberg, A., Wraith, R., 1995. A developmental model of childhood traumatic stress, in:
Cicchetti, D., Cohen, D. (Eds.), Manual of Developmental Psychopathology: Risk Disorder and
Adaptation. Wiley, New York, pp. 72–95.
Raine, A., 1993. The Psychopathology of Crime: Criminal Behavior as a Clinical Disorder. Academic
Press, Inc.: San Diego, CA, USA.
Reebye, P., Moretti, M.M., Wiebe, V.J., Lessard, J.C., 2000. Symptoms of posttraumatic stress
disorder in adolescents with conduct disorder: Sex differences and onset patterns. Can. J.
Psychiatry-Revue Can. Psychiatr. 45, 746–751.
Reich, W., Shayka, J.J., Taibleson, C., 1991. Manual to accompany the diagnostic interview for
children and adolescents. Revised. Washington University Press, St Louis (MI).
Resch, F., Brunner, R., 2004. Posttraumatische Belastungsstörung, Anpassungsstörungen und
Selbstbeschädigungserkrankungen, in: Eggers, C., Fegert, J.M., Resch, F. (Eds.), Psychiatrie Und
Psychotherapie Des Kindes- Und Jugendalters. Springer, Berlin, pp. 517–540.
Rhee, S.H., Lahey, B.B., Waldman, I.D., 2015. Comorbidity among dimensions of childhood
psychopathology: Converging evidence from behavior genetics. Child Dev. Perspect. 9, 26–31.
doi:10.1111/cdep.12102
Robins, L.N., Helzer, J.E., Cottler, L., Goldling, E., 1988. National Institute of Mental Health
Diagnostic Interview Schedule Version III - revised. Department of Psychiatry, Washington
University., St. Louis.
Ruan, W.J., Goldstein, R.B., Chou, S.P., Smith, S.M., Saha, T.D., Pickering, P., Dawson, D.A.,
Huang, B., Stinson, F.S., Grant, B.F., 2008. The Alcohol Use Disorder and Associated
Disabilities Interview Schedule-IV (AUDADIS-IV): Reliability of New Psychiatric Diagnostic
Modules and Risk Factors in a General Population Sample. Drug Alcohol Depend. 92, 27–36.
doi:10.1016/j.drugalcdep.2007.06.001.The
Ruchkin, V. V., Schwab-Stone, M., Koposov, R., Vermeiren, R., Steiner, H., 2002. Violence
Exposure, Posttraumatic Stress, and Personality in Juvenile Delinquents. J. Am. Acad. Child
Adolesc. Psychiatry 41, 322–329. doi:10.1097/00004583-200203000-00012
Schafer, I., Barkmann, C., Riedesser, P., Schulte-Markwort, M., 2006. Posttraumatic syndromes in
children and adolescents after road traffic accidents - a prospective cohort study.
Psychopathology 39, 159–164. doi:10.1159/000092676
Schepker, R., 1997. Posttraumatische Belastungsstörungen im Kindesalter –Diagnose,
Verlaufsprädiktoren und therapeutische Strategien. Z. Kinder. Jugendpsychiatr. Psychother. 25,
46–56.
Schwarzer, G., 2015. Package ―meta‖: General Package for Meta-Analysis [WWW Document]. URL
https://cran.r-project.org/web/packages/meta/meta.pdf.
Scott, S., Knapp, M., Henderson, J., Maughan, B., 2001. Financial cost of social exclusion: follow up
study of antisocial children into adulthood. BMJ 323, 191.
Sengupta, S.M., Fortier, M.-È., Thakur, G. a, Bhat, V., Grizenko, N., Joober, R., 2015. Parental
psychopathology in families of children with attention-deficit/hyperactivity disorder and exposed
to maternal smoking during pregnancy. J. Child Psychol. Psychiatry. 56, 122–129.
doi:10.1111/jcpp.12286
29
Simons, M., Herpertz-Dahlmann, B., 2008. Trauma and traumatic disorders in children and
adolescents-a critical overview of classification and diagnostic criteria. Z. Kinder.
Jugendpsychiatr. Psychother. 36, 151–61. doi:10.1024/1422-4917.36.3.151
Spitzer, R.L., Williams, J.B., 1987. Structured clinical interviewfrom DSM-III-R Non-Patient Version
modified for the Vietnam Veterans Readjustment Study. New York State Psychiatric Institute,
Biometrics Research, New York.
Spitzer, R.L., Williams, J.B.W., Gibbon, M., First, M.B., 1990. Structured clinical interview for DSM-
III-R—non-patient edition (SCID-NP, Version 1.0). American Psychiatric Press, Washington,
DC.
Stein, M.B., Walker, J.R., Forde, D.R., 2000. Gender differences in susceptibility to posttraumatic
stress disorder. Behav. Res. Ther. 38, 619–28. doi:http://dx.doi.org/10.1016/S0005-
7967%2899%2900098-4
Stein, M.B., Walker, J.R., Hazen, A.L., Forde, D.R., 1997. Full and Partial Posttraumatic Stress
Disorder: Findings From a Community Survey. Am. J. Psychiatry 154, 1114–1119.
Steiner, H., Garcia, I.G., Matthews, Z., 1997. Posttraumatic stress disorder in incarcerated juvenile
delinquents. J. Am. Acad. Child Adolesc. Psychiatry 36, 357–365. doi:10.1097/00004583-
199703000-00014
Stormshak, E.A., Bierman, K.L., McMahon, R.J., Lengua, L.J., 2016. Parenting Practices and Child
Disruptive Behavior Problems in Early Elementary School. J. Clin. Child Psychol. 29, 17–29.
doi:10.1207/S15374424jccp2901
Tagay, S., Repic, N., Düllmann, S., Schlottbohm, E., Hermans, E., Hiller, R., Holtmann, M., Frosch,
D., Senf, W., 2013. Traumatische Ereignisse, psychische Belastung und Prädiktoren der PTBS-
Symptomatik bei Kindern und Jugendlichen. Kindheit und Entwicklung 22, 70–79.
doi:10.1026/0942-5403/a000102
Viding, E., 2012. Antisocial behaviour in children with and without callous-unemotional traits. J. R.
Soc. Med. 105, 195–200.
Waltes, R., Chiocchetti, A.G., Freitag, C.M., 2015. The neurobiological basis of human aggression: A
review on genetic and epigenetic mechanisms. Am. J. Med. Genet. Part B Neuropsychiatr. Genet.
doi:10.1002/ajmg.b.32388
Wiebe, S.A., Clark, C.A.C., De Jong, D.M., Chevalier, N., Espy, K.A., Wakschlag, L., 2015. Prenatal
tobacco exposure and self-regulation in early childhood: Implications for developmental
psychopathology. Dev. Psychopathol. 27, 397–409. doi:10.1017/S095457941500005X
Wiebe, S.A., Fang, H., Johnson, C., James, K.E., Andrews Espy, K., 2014. Determining the Impact of
Prenatal Tobacco Exposure on Self-regulation at Six Months. Dev. Psychol. 50, 1746–1756.
doi:10.3851/IMP2701.Changes
Wolf, E.J., Miller, M.W., Krueger, R.F., Lyons, M.J., Tsuang, M.T., Koenen, K.C., 2010.
Posttraumatic Stress Disorder and the Genetic Structure of Comorbidity. J. Abnorm. Psychol.
Abnorm Psychol 119, 320–330. doi:10.1037/a0019035.Posttraumatic
Yong Ping, E., Laplante, D.P., Elgbeili, G., Hillerer, K.M., Brunet, A., O‘Hara, M.W., King, S., 2015.
Prenatal maternal stress predicts stress reactivity at 21/2 years of age: The Iowa Flood Study.
Psychoneuroendocrinology 56, 62–78. doi:10.1016/j.psyneuen.2015.02.015
Zannas, A.S., Provençal, N., Binder, E.B., 2015. Epigenetics of Posttraumatic Stress Disorder: Current
Evidence, Challenges, and Future Directions. Biol. Psychiatry 78, 327–335.
doi:10.1016/j.biopsych.2015.04.003
Zuckerman, M., 1979. Sensation Seeking: Beyond the Optimal Level of Arousal. Lawrence Erlbaum
Associates: Hillsdale, NJ, USA.

30
Figure1. Flow diagram for identifying studies on the prevalence and comorbidity of trauma, PTSD and
CD
Figure 2. Meta-analyses of the prevalence of PTSD in children and adolescents with CD
Figure 3. Possible developmental pathways of CD, trauma and PTSD

31
 Table 1. Summary of included studies after systematic literature research
First Year Cou Surve Desi Popula N Age Sex IQ Assessment of
Author ntr y g tion (Mean) trauma/PTSD and
y Years n CD (diagnostic
criteria)
Children /
Adolescents
Bur 1995 USA -2 CST CS_C 25 14- M 14, F 11 93.6 DICA-R-A (DSM-
ket D 17 III-R)
2
Co 2007 USA 1996- CST CS_C 53 4-17 M 47, F 6 - K-SADS-E (DSM-
nno 2005 D IV)
r
Gre 2015 Nor 2011- CST HRP 335(CD 12- M 139, F -2 CAPA (DSM-IV)
ger wa 2014 64) 23 196
y
Ilo 2012 Finla 2001- CST CS_C 155 12- M 92, F 63 -2 K-SADS-PL
mä nd 2006 D 17 (DSM-IV)
ki
Re 2000 Cana -2 CST CS_C 65 10- M 40, F 25 90.42 DICA-R (DSM-III-
eby da D 17 R)
e

Adults
Afi 2011 USA 2004- CST PBS 33175 >=2 M 13595, -2 AUDADIS-IV
fi 2005 (CD 0 F 19580 (DSM-IV)
1478) (CD M
969, F
509)
Di 2005 USA -2 CST VC 160 65- M -2 SCID (DSM-III-R)
kel 86
Dil 2007 USA 1993- CST VC 591 49- M -2 CIDI/ MS-PTSD
lar 1994 77 (DSM-III-R)
d
Ko 2002 USA 1992 CST VC 6744 36- M -2 DIS-R-III (DSM-
ene 55 III)
n1
AUDADIS-IV (DSM-IV)=Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV
Version (Ruan et al., 2008), CAPA (DSM-IV)=Child and Adolescent Psychiatric Assessment (Angold et al.,
1995), CIDI (DSM-III-R)=Composite International Diagnostic Interview (World Health Organization, 1994)
modified for the National Comorbidity Study by the University of Michigan (Kessler et al., 1994),
CS_CD=Clinical cases with CD, CST=Cross-sectional trial, DICA-R (DSM-III)=The Diagnostic Interview for
Children and Adolescents-Revised Adolescent Version (Reich, Shayka, & Taibleson, 1991), DICA-R-A (DSM-
III-R)=Diagnostic Interview for Children and Adolescents, Adolescent Version (Herjanic et al. 1977; revised
January 1990), DIS-R-III (DSM-III)=Mental Health Diagnostic Interview Schedule Version III-revised (Robins
et al., 1988), F=Female, HRP=high-risk population of adolescents in residential care units, K-SADS-E (DSM-
IV)=Schedule for Affective Disorders and Schizophrenia for School-age Children. Epidemiologic version-5 for
lifetime diagnoses (Orvaschel, 1995), K-SADS-PL (DSM-IV)=Finnish version of Schedule for Affective
Disorder and Schizophrenia for School-Age Children Present and Lifetime, M=Male, MS-PTSD (DSM-III-
R)=Mississippi Scale for Combat-Related Posttraumatic Stress Disorder (Keane, Caddell, & Taylor, 1988),
PBS= Population based study, SCID (DSM-III-R)=Structured Clinical Interview for DSM-III-R (SCID) Non-

32
Patient Version Modified for the Vietnam Veterans Readjustment Study (Spitzer & Williams, 1987) and the
SCID Non-Patient Edition (Spitzer, Williams, Gibbon, & First, 1990), VC=war veteran cases.
-1There are two additional publications from Koenen et al. (2005) and Fu et al. (2007)
presenting similar results from the same study sample.
-2Respective information not reported in publication.

33
Table 2. Summary of included studies presenting prevalence of trauma and/or PTSD with CD, N (%)
First Author Females Males Total
(Year) Without With CD Without With CD Without With CD
CD CD CD
Trau PT Trau PT Trau PT Trau PT Trau PT Trau PTS
ma SD ma SD ma SD ma SD ma SD ma D
Children /
Adolescents
– Clinical
Cases with CD
Burket -1 -1 -1 3 -1 -1 -1 1 -1 -1 -1 4
L
(1995), N=25 (27 (7) (16)
)L L
1 1 1 1 1 1 1 1 1 1 1
Connor - - - - - - - - - - - 6
(2007), N = 53 (11)
L
1 1 1 1 1 1 1 1 1
Ilomäki - - - 8 - - - 3 - - - 11
(2012), N=155 (13 (3)L (7)L
)L
Reebye -1 -1 -1 7 -1 -1 -1 4 -1 -1 -2 11
(2000), N = 65 (28 (10 (56) (17)
)C )C L C

– High risk
population
Greger -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -2 -1
(2015), (21)
P
N = 335 (CD
= 64)

Adults
– Population
based study
Afifi (2011), 164 168 486 105 1162 581 902 93 2802 226 1388 198
N = 33175 05 4 (96) (20 2 (92) (8)L 7 5 (93)
(CD = 1478) (8)L L
)L (85) (4)L L
(85) (6)L L
(11)
L L L
(84)
L

– Study with
war veterans
Koenen -1 -1 -1 -1 -2 -2 -2 -2 -1 -1 -1 -1
(2002), N = (38) (50 (53) (64
6477 )* )*
C
=Current prevalence. L =Lifetime prevalence. P =Point prevalence in last 3 months. -1 =Not assessed. -2
=Assessed, but not reported. * =PTSD prevalence after trauma exposure.

34
Figure1. Flow diagram for identifying studies on the prevalence and comorbidity of trauma, PTSD and CD

Records identified through Ebsco (PsycInfo, Records identified through PubMed

PsycArticles, PsycIndex) database searching database searching
01/1980-04/2016 01/1980-04/2016
(trauma and Conduct Disorder: (trauma and Conduct Disorder:
n =108) n =183)
Identification

(Posttraumatic Stress Disorder and Conduct (Posttraumatic Stress Disorder and Conduct
Disorder: Disorder:
n =144) n =205)
(PTSD and Conduct Disorder: (PTSD and Conduct Disorder:
n =132) n =179)
(n =384) (n =567)

All identified records trough Ebsco and Pubmed database searching

(n = 951)

Records after duplicates removed

1. Screening

(n = 524) Abstract-screening: Articles excluded because

- no human studies
- no information on CD and trauma or PTSD
- verb “conduct” not related to CD or “trauma”
in medical context (e.g. traumatic brain injury)
(n = 448)

Full-text articles assessed for eligibility

2. Screening

(n = 76)
Full-text-screening: Articles excluded because
- no DSM-criteria for CD, trauma and/or PTSD
fulfilled
- intervention or single case studies
(n = 67)

Studies included in qualitative synthesis

(n = 9)

Studies included in quantitative synthesis for

PTSD prevalence in children and adolescents
Included

with CD (meta-analysis)
(n = 4)

Studies included in quantitative synthesis

for PTSD prevalence in boys and girls with
CD (meta-analysis)
(n = 3)
Figure 2. Meta-analyses of the prevalence of PTSD in children and adolescents with CD
Figure 3. Possible developmental pathways of CD, trauma and PTSD