Relationship of parental trauma exposure and PTSD to PTSD, depressive and anxiety disorders in offspring

Relationship of parental trauma exposure and PTSD to PTSD,depressive and anxiety disorders in offspring

Rachel Yehuda*, Sarah L. Halligan, Linda M. Bierer

The Traumatic Stress Studies Program of the Mount Sinai School of Medicine and Bronx Veterans Affairs, New York, NY 10468, USA

Received 1 May 2001; received in revised form 3 July 2001; accepted 11 July 2001

Abstract

This study examined the relationship of parental trauma exposure and PTSD to the development of posttraumatic stress disorder

(PTSD), depressive and anxiety disorders in the adult offspring of Holocaust survivors. One hundred and thirty-five subjects (55men and 80 women) were divided into three groups according to parental trauma exposure and PTSD: 60 subjects were offspring ofHolocaust survivors who endorsed having at least one parent with PTSD, 33 were offspring of Holocaust survivors who reportedhaving no parent with PTSD, and 42 were demographically similar subjects with no parental Holocaust exposure. All subjects

underwent a comprehensive psychiatric interview in which information about lifetime psychiatric diagnoses and exposure to trau-matic events was obtained. Subjects also completed a checklist based on the 17 DSM-IV symptoms of PTSD, to estimate thesymptom severity of PTSD in their parents. A presumptive diagnosis of parental PTSD was assigned according to DSM-IV criteria.

Forward and forced entry stepwise logistic regression analyses were used to determine the effects of parental exposure, parentalPTSD, and the subject’s own history of trauma in the development of PTSD, depressive, and anxiety disorders in the offspring. Thefindings demonstrate a specific association between parental PTSD and the occurrence of PTSD in offspring. Additionally, parental

trauma exposure, more than parental PTSD, was found to be significantly associated with lifetime depressive disorder. The identi-fication of parental PTSD as a risk factor for PTSD in offspring of Holocaust survivors defines a sample in which the biological andpsychological correlates of risk for PTSD can be further examined. Published by Elsevier Science Ltd.

Keywords: Posttraumatic stress disorder; Risk factors; Holocaust survivors; Familial risk; Psychological trauma; Depression; Anxiety disorders; (PTSD)

1. Introduction

The specific type of psychopathology that developsover the lifetime of an individual is thought to be asso-ciated with both the nature of events experienced (e.g.whether life threat has been experienced) and the per-sonal predispositions of that individual based on theirfamily history of particular types of psychopathology(Dohrenwend, 2000). Early studies of posttraumaticstress disorder (PTSD) emphasized the importance oftrauma exposure as the major etiologic variable inPTSD. However, since only a proportion of traumaexposed persons develop PTSD (Kessler et al., 1995;Breslau et al., 1998; Perkonigg et al., 2000), it has also

been of interest to examine other contributors to thisdisorder, including familial risk factors (Yehuda andMcFarlane, 1995; Yehuda, 1999).In fact, the idea that familial psychiatric history may

contribute to posttraumatic symptoms predates thecurrent conceptualization of the diagnosis of PTSD.Among the earliest published findings of war veterans wereobservations of a greater family history of psychopathol-ogy in those who developed posttraumatic symptomscompared with those who did not. In 1918, Wolfsohndemonstrated that 74 of 100 patients with war neurosesreported a family history of psychoneurosis comparedto none of 100 matched subjects (Wolfsohn, 1918).Others found similar associations in World War I andWorld War II veterans and their families (Oppenheimerand Rothschild, 1918; Robey and Boaz, 1918; Swan,1921; Curran and Mallinson, 1940; Cohen et al., 1948;Speed et al., 1989), and in civilians exposed to disaster(McFarlane, 1988). Although these early studies arenoteworthy for their careful consideration of the nature

0022-3956/01/$ - see front matter Published by Elsevier Science Ltd.

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Journal of Psychiatric Research 35 (2001) 261–270

www.elsevier.com/locate/jpsychires

* Corresponding author at present address: Psychiatry OOMH,

Bronx Veteran Affairs Medical Center, 130 West Kingsbridge Road,

Bronx, NY 10468, USA. Tel. +1-718-584-9000, ext. 6964; fax: +1-

718-933-2121.

E-mail address: [email protected] (R. Yehuda).

of the event and consequent symptoms experienced bythe individual, neither the nature of familial mental illnessnor a direct relationship to PTSD versus other potentialco-occurring disorders in subjects was elucidated.More recent studies have confirmed that respondents

with PTSD are typically three times more likely thantrauma survivors without PTSD to report anxiety,depression, psychosis, and antisocial behavior in familymembers (Davidson et al., 1985, 1989, 1998; True et al.,1993; Watson et al., 1995; Reich et al., 1996; Yehuda etal., 1998b). In a sample that compared familial psycho-pathology in rape victims with PTSD, rape victimswithout PTSD, depressed patients, anxiety disorderpatients, and healthy controls, PTSD was associated withthe presence of major depressive disorder in first-degreerelatives (Davidson et al., 1998). However, this findingmay have been related to the presence of comorbiddepression in the rape victims with PTSD (Davidson etal., 1998).Although a family history of psychopathology, parti-

cularly depression, is clearly present in a substantialnumber of persons who develop PTSD, there are almostno studies that have specifically examined the relation-ship between PTSD in subjects and PTSD in parents. Inpart, this may be due to the fact that prior to 1980mental health workers did not make the diagnosis ofPTSD. As such, it would be difficult for subjects whohave been diagnosed with PTSD within the last twodecades to be aware of the presence of this disorder inparents, unless exposure to extreme trauma had been anotable presence in their parents’ lives. Indeed, it islikely that parents who did seek mental health treatmentprior to 1980 for symptoms related to trauma-exposurewere given the diagnosis of a mood or anxiety disorder.It may be for this reason that the literature in theaggregate only supports a link between PTSD andfamily history of psychopathology in general, ratherthan a specific family history of PTSD.However, it is critical to examine whether there is a

specific familial link between PTSD in parents and chil-dren, as this link would justify the search for a geneticbasis for this disorder. A tantalizing observation hasbeen the finding of an increased prevalence of PTSDamong trauma survivors who also had a twin withPTSD, compared to trauma survivors whose exposedtwin did not develop PTSD (True et al., 1993). The riskfor developing PTSD after trauma exposure was sig-nificantly greater for monozygotic than for dizygotictwins, suggesting a specific role for genetic factors inconferring susceptibility to the development of this syn-drome. True et al. also reported a significant geneticcontribution to degree of combat exposure, but the roleof genetic factors in symptom development remainedsignificant even once exposure was accounted for. Ofcourse, these data do not obviate the possibility thatenvironmental factors also play a role in the develop-

ment of PTSD. Regardless, the establishment of specificfamilial links in PTSD provides important insight intoputative risk factors for this disorder.We have recently demonstrated a greater prevalence

of PTSD in adult offspring of Holocaust survivorscompared to subjects whose parents had not beenexposed to the Holocaust (Yehuda et al., 1998c). Thesefindings constituted a replication and extension ofSolomon’s observations that Lebanon War veteranswho were children of Holocaust survivors had higherrates of PTSD, and a different clinical picture, com-pared to veterans of that war whose parents were notsurvivors (Solomon et al., 1988). However, in both thesestudies, PTSD was examined in relation to parentaltrauma exposure (i.e. the Holocaust) and not PTSD perse. In a small pilot study of 22 parent–child pairs, weobserved that PTSD was only present in offspring whohad at least one parent with chronic PTSD (Yehuda etal., 1998b).The present study examines the relationship between

PTSD in a group of offspring of Holocaust survivorsand parental PTSD (as inferred from symptoms ratedby the offspring), in order to explore the possibility thatparental PTSD is a specific risk factor for PTSD in off-spring. Since we have also observed an increased pre-valence of other psychiatric disorders in offspring,particularly depressive disorders and anxiety disordersother than PTSD (Yehuda et al., 1998c), we also exam-ined the relationship between parental PTSD and thedevelopment of these conditions. These analyses exam-ine the specificity of parental PTSD as a risk factor forPTSD, in contrast to other forms of psychopathology.

2. Methods

2.1. Participants

Fifty-five men and 80 women provided informedconsent to participate in this IRB-approved study, fol-lowing a detailed explanation of all procedures. Holo-caust survivor offspring were defined as having beenborn to at least one biological parent who experiencedthe Nazi Holocaust. For the purposes of the currentstudy, Holocaust survivors were individuals who were ina ghetto, a labor or concentration camp, or had to hidein or flee Nazi-occupied territory. The comparison par-ticipants were Jewish individuals in the same age rangewho did not have a parent who was a Holocaust survi-vor. Importantly, comparison subjects were not chosento be without psychiatric diagnoses, but were recruitedand selected only on the basis of being demographicallysimilar to Holocaust offspring, with the exception ofparental exposure.Recruitment for the study was as previously described

(Yehuda et al., 2000). Primarily, participants were solicited

262 R. Yehuda et al. / Journal of Psychiatric Research 35 (2001) 261–270

from lists obtained from the Jewish community orresponded to community group announcements andnewspaper advertisements (n=109). Others volunteeredafter taking part in short-term group psychotherapy atthe Mount Sinai Specialized Treatment Program forHolocaust Survivors and their Families (n=26). Sincewe could only study those who willingly approached us,it is possible that symptomatic individuals are over-represented in this sample. The fact that 28% of theoffspring had sought, or were seeking treatment in ourclinic suggests a sampling bias towards offspring whofreely endorse mental health symptoms.The current report includes 93 subjects (69 offspring

and 24 comparison subjects falling within the same agerange) from previous studies (Yehuda et al., 1998c), forwhom information regarding parental PTSD had beenobtained. In addition, 42 new participants (26 offspringand 16 comparison participants) were recruited since theprior publications.

2.2. Clinical assessments

All participants in the current study were screened forAxis I disorders using the mental health screeningquestions from the Structured Clinical Interview forDSM-IV (SCID; Spitzer et al., 1995). Participants whopositively endorsed one or more of these questions werethen given a complete diagnostic interview using theSCID by a trained clinical rater. Exposure to traumawas assessed using the Trauma History Questionnaire(Green, 1996), which lists a range of traumatic events inseveral major areas (crime, accident and disaster, physi-cal and sexual assault). Participants endorsed any eventsfrom this list that they had experienced, and also listedany other personal experiences that might have beenparticularly distressing or frightening. The details ofthese events were then discussed in order to ascertainwhich (if any) met diagnostic criterion for a traumaticevent as defined by DSM-III-R or DSM-IV. Followingthis exploration, the Clinician Administered PTSDScale (CAPS; Blake et al., 1995) was administered to allparticipants who reported a traumatic event. Partici-pants who identified more than one trauma were askedto identify their most distressing event, and this wasused as the basis for the evaluation of current and life-time PTSD.In addition to the clinical interview, participants

completed the Parental PTSD Scale. This scale, devel-oped by our group for use in offspring of Holocaustsurvivors, was given to participants in order to assessparental Holocaust-related PTSD (Yehuda et al., 2000).The scale requires participants to detail their parents’Holocaust experiences, if any (e.g. ghetto, concentrationcamp, in hiding). For each parent who experienced theHolocaust, participants then completed a checklistbased on the 17 DSM-IV symptoms of PTSD, rating

severity on a 4-point Likert scale. Presence or absence ofsymptoms was derived from these ratings, and a pre-sumptive diagnosis of PTSD assigned according toDSM-IV criteria. Although the accuracy of an adultchild’s estimate of the actual extent of parental PTSDsymptoms is difficult to ascertain, the questionnaireprovided an index of the subjective perception of theparent’s symptoms. Furthermore, preliminary evidencesuggests that this scale correlates well with independentdiagnostic evaluations. In 11 subjects, we were able tocompare results of this questionnaire with results ofCAPS scores from parents whom we had intervieweddirectly. With one exception, ratings based on clinicalevaluations and those based on scores assigned by off-spring indicated the same conclusion regarding the pre-sence or absence of PTSD in the parent. In the case ofthe single discrepancy, clinical data suggested that bothparents had had lifetime PTSD, whereas the adult childperceived only her father to have suffered from PTSD.For comparability with other ratings in these analyses,the adult offspring’s impression was used rather thanthe clinician-rated CAPS data. However, in three cases,estimates of severity of parental PTSD were madedirectly from their CAPS data due to missing orincomplete responses of the offspring.The Parental PTSD Scale also included a short screen

for parental exposure to traumatic events (e.g. combat,accident or natural disaster, and physical or sexualassault, in addition to types of Holocaust experiences).This section of the scale was administered to compar-ison subjects as well as to Holocaust survivor offspring,in order to estimate the likelihood of parental PTSD inthe former group. None of the participants in the com-parison group reported parental exposure to trauma onthis measure. The extent to which offspring are aware ofsuch experiences in their parents is unknown, and par-ents may not have disclosed personal experiences, suchas physical or sexual assault, to their offspring. How-ever, events that are relevant to the current study, i.e.that were of a relatively large magnitude or that have anongoing impact on the parent, are more likely to bedetected.

2.3. Statistical analyses

In order to examine the contributions of parentaltrauma exposure and parental PTSD to the develop-ment of psychiatric disorders in offspring, the samplewas divided into three groups. The no parental exposuregroup consisted of Jewish comparison subjects who didnot have Holocaust survivor parents. The parentalexposure group consisted of Holocaust survivor off-spring, neither of whose parents had PTSD. The par-ental PTSD group consisted of Holocaust survivoroffspring who had one or two parents with PTSD. Chisquare tests and analysis of variance (ANOVA) were

R. Yehuda et al. / Journal of Psychiatric Research 35 (2001) 261–270 263

used to assess group differences in demographic vari-ables, and lifetime exposure to traumatic stress.ANOVA was used to assess the effects of group and

gender on the mean number of lifetime psychiatricdiagnoses per individual. Post-hoc comparisons usingTukey’s HSD test, or Dunnett’s T3 where varianceswere unequal, were carried out between pairs of groups.Based on the observed distribution of diagnoses,depressive and anxiety disorders other than PTSD weregrouped into their respective diagnostic categories forthe purpose of data analysis.Forward stepwise logistic regression was used to

assess the contribution of group (no parental exposure,parental exposure without PTSD, parental exposurewith PTSD) to the occurrence of different psychiatricdiagnoses in the sample, controlling for gender. Wheregroup emerged as a significant predictor of diagnosticcategory (i.e. PTSD and depressive disorders), forcedentry stepwise logistic regression was used in order todistinguish between the effects of parental exposure andparental PTSD, since offspring in the parental PTSDgroup had both of these potential risk factors. Further-more, as trauma exposure is a necessary prerequisite ofPTSD, this was included in an additional forward step-wise logistic regression procedure in order to compare awider set of potential contributors to psychopathology.To control for gender effects, this variable was forcedinto the logistic regression analyses as the first step.A second set of analyses specifically examined the

impact of parental PTSD on offspring mental health byconfining analyses to subjects with parental Holocaustexposure. Chi square tests examined the overall rela-tionship between parental PTSD (no parental PTSD,paternal PTSD only, maternal PTSD only, or bothparents with PTSD) and the occurrence of psychiatricdiagnoses in offspring (i.e. PTSD, depressive disorders,and anxiety disorders other than PTSD). Where a sig-nificant relationship was found, post hoc chi squaretests were performed between pairs of groups, withdegrees of freedom for these tests being corrected toreflect the four group design from which the pairs weredrawn (Fleiss, 1982). Additionally, forced entry stepwiselogistic regression was used to examine maternal andpaternal PTSD as independent predictors of the pre-sence or absence of pathology in the offspring. Pairs ofanalyses were carried out, with maternal or paternalPTSD entered into the regression equation first. In thisway, we assessed the independent contributions ofmaternal and paternal PTSD to psychopathology in theoffspring, each controlled for the other.

3. Results

Of the 93 Holocaust survivor offspring studied, 60 (23men and 37 women) endorsed having at least one parent

with PTSD, forming the ‘‘parental PTSD’’ group.Thirty-three Holocaust survivor offspring (eight menand 25 women) reported having no parent with PTSD,and were designated the ‘‘parental exposure’’ group,to distinguish them from demographically similar sub-jects in the ‘‘no parental exposure’’ group (24 men, 18women). There was a significant difference in genderdistribution (w2=8.54, d.f.=2, P=0.014), reflecting ahigher proportion of women in the parental PTSD andparental exposure groups relative to the no parentalexposure group. The three groups were comparable inage (parental PTSD group: 40.2�6.6 years; parentalexposure group: 40.1�7.1 years; no parental exposuregroup: 38.5�8.6 years). Years of education were alsocomparable among the groups (parental PTSD group:17.3�2.8 years; parental exposure group: 17.3�2.3years; no parental exposure group: 18.2�2.4 years),indicating a mean graduate level of education. Almostall subjects were employed, or were unemployed bychoice (i.e. spouses). Importantly, there were no groupdifferences in the number of lifetime potentially trau-matic events as reported on the THQ (group: F=0.37,d.f.=2103, n.s.; gender: F=1.92, d.f.=1103, n.s.; groupby gender interaction: F=2.14, d.f.=2103, n.s.).When the sample was considered as a whole, 40.7%

(n=55) had no lifetime psychiatric Axis I disorder,31.1% (n=42) had a single disorder, 14.1% (n=19) hadtwo disorders, 10.4% (n=14) had three disorders, 2.2%(n=3) had four disorders, and 1.5% (n=2) met criteriafor six disorders. Diagnoses present in the sample wereas follows: PTSD (23.7%), major depressive disorder(32.6%), dysthymia (8.9%), bipolar disorder (1.5%),mood disorder not otherwise specified (3.0%), general-ized anxiety disorder (12.6%), panic disorder (5.9%),phobias (6.0%), hypochondriasis (0.7%), anxiety dis-order not otherwise specified (0.7%), anorexia (1.5%),bulimia nervosa (2.2%), eating disorder not otherwisespecified (0.7%), alcohol and cannabis substance abuse(3.7%), body dysmorphic disorder (0.7%), and adjust-ment disorder (0.7%). Subjects may have met the diag-nostic criteria for one or more of these disorders atseparate times or contemporaneously. Of subjects withlifetime PTSD (n=32), 72% also had a history ofdepressive disorder(s) and 31% of anxiety disorder(s)other than PTSD. Of the subjects with lifetime depres-sive disorders (n=57), 40% had a history of PTSD and28% had a history of anxiety disorder(s). Of the subjectswith lifetime anxiety disorders (n=30), 33% had a his-tory of PTSD and 53% had a history of depressive dis-order(s).Fig. 1 shows the mean number of lifetime psychiatric

diagnoses by group (i.e. no parental exposure, parentalexposure only, parental PTSD). A two-way ANOVAassessed the effects of gender and group on the numberof offspring lifetime psychiatric diagnoses. There was ahighly significant main effect of group on number of


diagnoses (F=1.50, df=2.129, P<0.0005), but no maineffect of gender (F=1.48, df=1.129, n.s.), and no groupby gender interaction (F=0.38, df=2.129, n.s.). Post-hoc tests using Dunnett’s T3 demonstrated significantlyfewer diagnoses in the no parental exposure group rela-tive to both the parental exposure (P=0.038) and theparental PTSD (P<0.0005) group. There was also atrend for the parental PTSD group to have more life-time diagnoses than the parental exposure group(P=0.094). These results demonstrate that the numberof diagnoses among offspring is associated with parentalexposure, and suggest that there may be an additionaleffect of parental PTSD.Based on the frequency of different diagnoses

observed in the sample, disorders were examined inthree major categories: PTSD, depressive disorders, andanxiety disorders other than PTSD. Other diagnoses(i.e. eating disorders and substance use disorders)occurred at too low a frequency to permit meaningfulanalyses. Fig. 2 shows the prevalence of psychiatricdiagnoses by gender in each of the three groups. Logis-tic regression demonstrated that gender was a sig-nificant predictor of the occurrence of depressivedisorders, with a higher frequency of depressive dis-orders occurring in women (w2=6.7, df=1, P=0.010).However, gender was not a significant predictor ofPTSD (w2=0.7, df=1, n.s.), or of anxiety disordersother than PTSD (w2=0.9, df=1, n.s.). Group was asignificant predictor of the occurrence of PTSD(w2=16.3, df=2, P<0.0005) and depressive disorders(w2=24.9, df=2, P<0.0005), after controlling for gen-der. There was also a trend for group to predict theoccurrence of anxiety disorders other than PTSD(w2=5.7, df=2, P=0.058).

As already reported, many of the Holocaust survivoroffspring had more than one lifetime psychiatric diag-nosis, raising the possibility of a generic vulnerability topsychopathology in offspring in relation to familial fac-tors. Thus, we wished to examine whether reportedassociations of parental group with PTSD, depressivedisorders, and, to a lesser extent, anxiety disorders otherthan PTSD, reflect distinct vulnerabilities to the differ-ent diagnoses. We therefore performed a second set oflogistic regression analyses, examining the group effecton the occurrence of PTSD, depressive and anxiety dis-orders, each while controlling for the other diagnosticcategories. Group was still a significant predictor of theoccurrence of offspring PTSD (w2=10.36, df=2,P=0.006), after controlling for gender, and for moodand other anxiety disorders. Group was similarly pre-dictive of depressive disorders in the offspring(w2=17.95, df=2, P<0.0005), after controlling forgender, and for PTSD and other anxiety disorders. Foranxiety disorders other than PTSD, group was nolonger predictive at a trend level after controlling forgender, PTSD, and depressive disorders (w2=4.2, df=2,n.s.). Thus, neither the prediction of offspring PTSD ordepressive disorders were artifacts of comorbidity, sinceassociations with parental group were retained evenafter controlling for the other diagnoses.Since parental group was a significant predictor of

offspring PTSD and depressive disorders, forced entrystepwise logistic regression was used to assess whether itwas presence or absence of parental exposure to theHolocaust (with or without PTSD), or the presence orabsence of parental PTSD that best accounted forPTSD and depression in offspring. For offspring PTSD,after controlling for gender (w2=0.71, df=1, n.s.), themost significant predictor in the forward logistic regres-sion was parental PTSD (w2=15.97, df=1, P<0.0005).After controlling for parental PTSD, there was noadditional contribution of Holocaust exposure in theprediction of PTSD in offspring (w2=0.29, df=1, n.s.).Conversely, in a second logistic regression analysis, once

Fig. 1. Mean number of lifetime psychiatric diagnoses in relation to

parental Holocaust exposure and PTSD status. Data represent means

and standard deviations.

Fig. 2. Parental Holocaust exposure and parental PTSD in relation to

PTSD, depressive and anxiety disorders in offspring. Data represent

the percentage of subjects who met criteria for these conditions.


gender and parental Holocaust exposure (w2=4.57,df=1, P=0.033) were controlled for, parental PTSDstill contributed strongly to the prediction of PTSD inoffspring when entered in a third step (w2=11.69, df=1,P=0.001). These results indicate that parental PTSDwas a more significant predictor of offspring PTSD thanparental Holocaust exposure.For depressive disorders, after controlling for gender

(w2=6.69, df=1, P=0.010), the most significant pre-dictor in the forward logistic regression analysis wasparental Holocaust exposure (w2=21.73, df=1,P<0.0005). The remaining variable of parental PTSDonly attained a trend level of significance in contributingto the prediction of depressive disorders (w2=3.12,df=1, P=0.077). In a second analysis, when parentalPTSD was forced into the logistic equation prior toparental exposure, there was a highly significant con-tribution (w2=16.93, df=1, P<0.0005); however, par-ental exposure still made an additional significantcontribution (w2=7.92, df=1, P=0.005). These resultsdemonstrate that depressive disorders are more stronglyrelated to parental Holocaust exposure than to parentalPTSD.Trauma exposure is a necessary prerequisite for the

development of PTSD, and may be instrumental in thedevelopment of depressive disorder. Therefore, weexamined the relative contributions of personal traumaexposure (i.e. an event of sufficient significance to havewarranted clinical assessment of PTSD with the CAPS)and parental group to the prediction offspring psycho-pathology. Logistic regression, controlling for gender, con-firmed that personal trauma exposure was the mostsignificant predictor of PTSD in offspring (w2=28.27,df=1, P<0.0005), followed by a significant contribu-tion of parental PTSD in the second step (w2=7.98,df=1, P=0.005). Thus, although subjects’ exposure totrauma contributed substantially to the development ofPTSD, parental PTSD was still a significant predictoronce personal trauma exposure was accounted for.When this analysis was repeated for depressive dis-orders, after gender, the model included two additionalsignificant steps, the first showing a substantial con-tribution for parental Holocaust exposure (w2=21.73,df=1, P<0.0005) and the second for personal traumaexposure (w2=10.69, df=1, P<0.001). Thus, traumaexposure also contributed to the development ofdepression in the current sample, independently of par-ental factors.Fig. 3 illustrates the prevalence of psychiatric diag-

noses in the offspring groups, with the parental PTSDgroup further broken down by paternal and/or maternalPTSD. Four offspring sub-groups were defined: no par-ental PTSD, maternal PTSD only, paternal PTSD only,and both maternal and paternal PTSD. When chisquare analyses were performed, there was a significanteffect of parental PTSD sub-groups on the occurrence

of offspring PTSD (w2=13.9, df=3, P=0.003). Post-hoc tests comparing all pairs of sub-groups, indicatedthat this effect was significant only for offspring withtwo parents vs. no parent with PTSD (w2=12.83, df=3,P=0.005). There was a trend for offspring with mater-nal PTSD to have a higher incidence of PTSD than off-spring with no parental PTSD (w2=7.26, df=3,P=0.06), but offspring with paternal PTSD were notsignificantly different from those without any parentalPTSD. No significant differences were found betweenoffspring groups defined by parental PTSD diagnosis inthe occurrence of depressive disorders (w2=2.32, df=3,n.s.) or anxiety disorders other than PTSD (w2=5.3,df=3, n.s.).In a second analysis, logistic regression was used to

examine the respective effects of paternal and maternalPTSD, and each controlling for the effect of the other.In a forced entry stepwise logistic regression, maternalPTSD was a significant predictor of offspring PTSD(w2=12.73, df=1, P<0.0005), but paternal PTSD didnot make a significant additional contribution(w2=1.84, df=1, n.s.), and neither did the interaction ofmaternal and paternal PTSD (w2= 0.20, df=1, n.s.). Ina second logistic regression, when paternal PTSD wasforced into the regression equation first, it attained sig-nificance (w2=3.90, df=1, P=0.048), with maternalPTSD still making a significant contribution (w2=10.67,df=1, P=0.001). Thus, the differences in the rates ofoffspring PTSD among the four subgroups are accoun-ted for principally by the effect of maternal PTSD. If theeffect of maternal PTSD is accounted for, the effect ofpaternal PTSD loses its significance.

4. Discussion

The major finding of this study is that of a strongrelationship between parental PTSD and the occurrenceof PTSD in offspring. Parental Holocaust exposure in

Fig. 3. Maternal and paternal PTSD, in relation to PTSD, depression,

and anxiety disorders in Holocaust survivor offspring. Data represent

the percentage of subjects who met criteria for these conditions.


the absence of PTSD was not a strong predictor of off-spring PTSD. Rather, parental Holocaust exposure wasa strong predictor of lifetime depressive disorders. Fur-ther, the total number of lifetime psychiatric disorderswas found to be substantially higher in offspring ofHolocaust survivors than in comparison subjects, withdepressive disorders reported with the greatest frequency.The observed relationship between parental and off-

spring PTSD provides support for the hypothesis thatpre-existing vulnerabilities may be critical in determin-ing how an individual responds to trauma (Yehuda,1999). PTSD is not a unique outcome following expo-sure to trauma, and depressive disorders have beenobserved in prospective studies as common sequelae oftraumatic experiences (Green et al., 1992; Shalev et al.,1998; Breslau et al., 2000). Personal trauma exposurewas associated with both PTSD and depression in thissample. However, our observation of higher rates ofPTSD in individuals with parental PTSD was found inthe absence of higher rates exposure to potentiallytraumatic events.PTSD and depressive disorders are associated with

different neurobiological alterations, particularly instress response systems (Reich et al., 1996; Yehuda etal., 1996). Therefore, it has been challenging to explainwhy trauma sometimes results in depression, sometimesresults in PTSD, and sometimes results in the co-occur-rence of these conditions. In the absence of other riskfactors or exposure-related variables, it may be thatPTSD is more likely to develop following trauma inthose with a pre-existing vulnerability related to familyhistory.The idea of pre-existing vulnerability to PTSD is also

relevant in considering the heterogeneous responseobserved in Holocaust survivor parents. The Holocaustwas an overwhelmingly extreme and life-altering eventfor those who experienced it. However, despite theinarguable magnitude of this trauma, not all Holocaustsurvivors developed PTSD, or any psychiatric disorder(Yehuda et al., 1997). The psychological literature hasfocused on the remarkable coping abilities, resilienceand fortitude of survivors in equal proportion tostudies of mental health impairments in this group.Thus, variability in survivors’ proneness to PTSD, par-ticularly chronic PTSD, may also reflect specific vulner-abilities, ranging from personality characteristics toalterations in genes that influence biological stressresponses. Clearly these risk factors could have beentransmitted to the offspring. Indeed, prior research hasalready established a role for genetic factors in thedevelopment of PTSD (True et al., 1993), and it is cer-tainly possible that genetic factors also underlie therelationship between parental and offspring PTSDobserved in the current paper. Alternatively, theobserved risk for PTSD in offspring of Holocaust sur-vivors may be a consequence of the expression of PTSD

in the parent. For example, the risk may reside in the‘environment’ created in homes where one or both par-ents suffered from a chronic mental illness. We haverecently reported that Holocaust survivor offspring withparental PTSD have higher rates of self-reported emo-tional abuse and physical neglect than offspring withoutparental PTSD (Yehuda et al., in press).Regardless of the etiology, our findings raise the pos-

sibility that vulnerability to PTSD is ‘transmitted’ acrossgenerations. Interestingly, maternal PTSD appeared tobe a stronger predictor of offspring PTSD than paternalPTSD. This finding requires replication with a largersample of participants with only paternal PTSD. None-theless, in the spirit of hypothesis generation it is rea-sonable to speculate about why the effects of maternalPTSD might be greater than the effects of paternalPTSD. It is possible, for example, that there may havebeen in utero effects of stress on the fetus. There isalready preliminary evidence that prenatal stress has arole in the development of offspring depression. Watsonet al. (1999) studied the effects of prenatal exposure to alarge earthquake in China. When offspring of exposedmothers were studied in adolescence, second trimestermaternal exposure to the earthquake was found to beassociated with higher rates of unipolar depression inmale, but not female, offspring. Many Holocaust survi-vor offspring were conceived immediately after the war,at a time when re-adjustment and re-integration pro-blems of parents may have impacted on nutritional,psychological, and other important prenatal factors.Alternatively, the findings of a greater effect of maternalPTSD may be the consequence of a dysfunction in theearly mother–child relationship. In the decades follow-ing World War II, the mother was generally the princi-pal caregiver. Thus, psychiatric impairment of themother during development may have had more impacton the offspring than impairment of the father. Indeed,disruptions in maternal rearing behaviors have recentlybeen implicated even in transgenerational animal mod-els of stress vulnerability (Francis et al., 1999).Parental PTSD may be so strong a risk factor as to

override the observed gender bias in this disorder, atleast in the current sample. In the present study, thewell-established gender effect in PTSD (Breslau et al.,1998) was not observed. In contrast, the gender bias indepressive disorder (Boyd and Weissman, 1981) wasapparent in this sample (Myers et al., 1984; Weissman etal., 1984a).Although we were initially interested in linking par-

ental PTSD with PTSD in offspring, we observed thatdepressive disorders were much more prevalent thanPTSD in the current sample of Holocaust survivor off-spring (56 vs. 29%, respectively). Trauma exposure is anecessary prerequisite of PTSD, whereas depressive dis-order can occur without such exposure. Thus, in theabsence of considering the contribution of parental


PTSD, the higher prevalence of depressive disordersrelative to PTSD could have simply been attributed tothe fact that not all offspring experienced a lifetimetraumatic event. However, even after controlling for thepresence of personal trauma history, it was apparentthat the elevated rates of depressive disorder were asso-ciated with parental Holocaust exposure. Thus, thefamily history variables associated with the develop-ment of PTSD and depression in offspring are some-what different, the former being related to parentalPTSD and the latter to parental trauma. However, thepossibility for the co-occurrence of these disorders iseasily understood, since parental exposure is also anecessary prerequisite of parental PTSD. Indeed, in thepresent sample, most of the subjects who had developedPTSD also had a depressive disorder, whereas only aminority of those with a depressive disorder also devel-oped PTSD.The particular focus on parental PTSD in the current

study stemmed from our initial observations of Holo-caust survivors, recruited from community, non-treat-ment-seeking populations. Approximately half of thesesurvivors met the diagnostic criteria for PTSD, but farfewer met criteria for a current depressive disorder(Yehuda et al., 1995, 1998c). We therefore believed thatPTSD might be the principal and most enduring psy-chopathologic consequence of Holocaust exposure.However, given the high prevalence of depressive dis-orders in this sample of children of Holocaust survivors,and the high rate of comorbidity observed, a more thor-ough exploration of the relationship between depressionand PTSD in Holocaust survivor parents and depressionin their offspring is warranted.Indeed, there are also intergenerational risk factors

associated with depressive disorders (Ashby and Crowe,1978; Weissman et al., 1984b; Klein, 1990; Cassano etal., 1992; Holsboer et al., 1995). Therefore, it is con-ceivable that offspring who developed depression alsohad parents that suffered from depression. In theabsence of knowledge of parental psychopathologyother than PTSD, it is not possible to draw conclusionsabout the relationship between other types of psychia-tric diagnoses in parents and offspring from these data.This is a limitation of the current study.An additional limitation is the assignment of parental

PTSD diagnosis based on offspring symptom ratings oftheir parents. Prior research comparing the family his-tory method to direct interview has indicated that itshows relatively high specificity in the detection offamilial psychopathology. In contrast, the sensitivity ofthis method is generally low, and as such it may result inan underestimation of diagnoses in family members(Mendlewicz et al., 1975; Orvaschel et al., 1982; Connorand Davidson, 1997; Davidson et al., 1998). In addition,it is conceivable that offspring reports of parentalsymptoms may have been influenced by their own psy-

chopathology, as well as by the severity of symptoms inthe parent. Given that Holocaust exposure was not asecret in the homes of survivors, we believe that thebehavioral consequences of PTSD (e.g. reliving phe-nomena; reports of nightmares and insomnia; distressand avoidance relating to reminders; irritability andoutbursts of anger; hypervigilance and increased startle)may have been reasonably evident to offspring. How-ever, the extent to which the findings of this study indi-cate a familial effect can only be confirmed with directevaluation of parental symptoms.The identification of parental PTSD as a risk factor

for PTSD among offspring of Holocaust survivors isimportant because it identifies a sample in which thebiological correlates of risk for PTSD can be examined.Our preliminary studies have provided support for theidea that low cortisol levels in PTSD may be related tothe risk for developing PTSD, as well as to the patho-physiological expression of the disorder (McFarlane etal., 1997; Yehuda et al., 1998a, 2000). The current studyalso underscores the important risk factor of parentaltrauma exposure as a putative risk factor for depression,and possibly other anxiety disorders. Moreover, itclearly identifies a personal history of trauma exposureas a significant contributor to the development ofdepressive disorders, although less so than parentaltrauma exposure in this sample. Insofar as PTSD anddepression have been associated with distinct biologicalalterations, the application of biologic studies to thesehigh risk groups offers an opportunity to form definitiveconclusions about interrelationships among correlatesof PTSD and depression as they relate to vulnerability,exposure, and illness.

Acknowledgements

The authors thank Ilana Breslau, M.A., Susan Dolan,B.A. and Ariel Penkower, B.A. for recruiting, screeningand evaluating subjects. The authors also thank the staffat the Specialized Treatment Program for HolocaustSurvivors and their Families, particularly RobertGrossman, M.D., Medical Director, for help with med-ical and diagnostic evaluations, and Dr. James Schmei-dler for statistical consultation. This work wassupported by NIMH grant MH-49555 (Dr. Yehuda).

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Relationship of parental trauma exposure and PTSD to PTSD, depressive and anxiety disorders in offspring