Adult Offspring Of Holocaust Survivors Research Articles

Intergenerational Effects of Maternal Holocaust Exposure on FKBP5 Methylation.

There is growing evidence that exposure to trauma prior to conception can affect offspring. The authors have reported that adult offspring of Holocaust survivors showed lower methylation of FK506 binding protein 5 (FKBP5) intron 7, site 6 compared with Jewish comparison volunteers. The present study sought to replicate this finding in a larger sample and to examine parental and offspring correlates of observed effects. Cytosine methylation was measured in blood using pyrosequencing. The independent replication sample consisted of 125 Holocaust offspring and 31 control subjects. Additional analyses, performed in a larger sample of 147 offspring and 40 control subjects that included the 31 previously studied participants, examined associations of parental trauma-related variables (i.e., sex of the exposed parent, parental posttraumatic stress disorder, age at Holocaust exposure) and offspring characteristics (i.e., childhood trauma exposure, lifetime psychiatric diagnoses, psychotropic medication use, FKBP5 rs1360780 genotype, FKBP5 gene expression, and neuroendocrine measures) with offspring FKBP5 methylation. FKBP5 site 6 methylation was significantly lower in Holocaust offspring than in control subjects, an effect associated with maternal Holocaust exposure in childhood and with lower offspring self-reported anxiety symptoms. FKBP5 gene expression was elevated in Holocaust offspring. FKBP5 methylation was associated with indices of glucocorticoid sensitivity but not with basal FKBP5 gene expression. This study replicates and extends the previously observed decrement in FKBP5 intron 7, site 6 methylation in Holocaust offspring. The predominance of this effect in offspring of mothers exposed during childhood implicates maternal developmental programming as a putative mechanism.

Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in Holocaust survivor offspring.

Differential effects of maternal and paternal posttraumatic stress disorder (PTSD) have been observed in adult offspring of Holocaust survivors in both glucocorticoid receptor sensitivity and vulnerability to psychiatric disorder. The authors examined the relative influences of maternal and paternal PTSD on DNA methylation of the exon 1F promoter of the glucocorticoid receptor (GR-1F) gene (NR3C1) in peripheral blood mononuclear cells and its relationship to glucocorticoid receptor sensitivity in Holocaust offspring. Adult offspring with at least one Holocaust survivor parent (N=80) and demographically similar participants without parental Holocaust exposure or parental PTSD (N=15) completed clinical interviews, self-report measures, and biological procedures. Blood samples were collected for analysis of GR-1F promoter methylation and of cortisol levels in response to low-dose dexamethasone, and two-way analysis of covariance was performed using maternal and paternal PTSD as main effects. Hierarchical clustering analysis was used to permit visualization of maternal compared with paternal PTSD effects on clinical variables and GR-1F promoter methylation. A significant interaction demonstrated that in the absence of maternal PTSD, offspring with paternal PTSD showed higher GR-1F promoter methylation, whereas offspring with both maternal and paternal PTSD showed lower methylation. Lower GR-1F promoter methylation was significantly associated with greater postdexamethasone cortisol suppression. The clustering analysis revealed that maternal and paternal PTSD effects were differentially associated with clinical indicators and GR-1F promoter methylation. This is the first study to demonstrate alterations of GR-1F promoter methylation in relation to parental PTSD and neuroendocrine outcomes. The moderation of paternal PTSD effects by maternal PTSD suggests different mechanisms for the intergenerational transmission of trauma-related vulnerabilities.

Elevation of 11β-hydroxysteroid dehydrogenase type 2 activity in Holocaust survivor offspring: evidence for an intergenerational effect of maternal trauma exposure.

Adult offspring of Holocaust survivors comprise an informative cohort in which to study intergenerational transmission of the effects of trauma exposure. Lower cortisol and enhanced glucocorticoid sensitivity have been previously demonstrated in Holocaust survivors with PTSD, and in offspring of Holocaust survivors in association with maternal PTSD. In other work, reduction in the activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), which inactivates cortisol, was identified in Holocaust survivors in comparison to age-matched, unexposed Jewish controls. Therefore, we investigated glucocorticoid metabolism in offspring of Holocaust survivors to evaluate if similar enzymatic decrements would be observed that might help to explain glucocorticoid alterations previously shown for Holocaust offspring. Holocaust offspring (n=85) and comparison subjects (n=27) were evaluated with clinical diagnostic interview and self-rating scales, and asked to collect a 24-h urine sample from which concentrations of cortisol and glucocorticoid metabolites were assayed by GCMS. 11β-HSD-2 activity was determined as the ratio of urinary cortisone to cortisol. Significantly reduced cortisol excretion was observed in Holocaust offspring compared to controls (p=.046), as had been shown for Holocaust survivors. However, 11β-HSD-2 activity was elevated for offspring compared to controls (p=.008), particularly among those whose mothers had been children, rather than adolescents or adults, during World War II (p=.032). The effect of paternal Holocaust exposure could not be reliably investigated in the current sample. The inverse association of offspring 11β-HSD-2 activity with maternal age at Holocaust exposure is consistent with the influence of glucocorticoid programming. Whereas a long standing reduction in 11β-HSD-2 activity among survivors is readily interpreted in the context of Holocaust related deprivation, understanding the directional effect on offspring will require replication and further exploration.

Coping in old age with extreme childhood trauma: Aging Holocaust survivors and their offspring facing new challenges

Objective: The Holocaust has become an iconic example of immense human-made catastrophes, and survivors are now coping with normal aging processes. Childhood trauma may leave the survivors more vulnerable when they are facing stress related to old age, whereas their offspring might have a challenging role of protecting their own parents from further pain. Here we examine the psychological adaptation of Holocaust survivors and their offspring in light of these new challenges, examining satisfaction with life, mental health, cognitive abilities, dissociative symptoms, and physical health. Methods: Careful matching of female Holocaust survivors and comparison subjects living in Israel was employed to form a case-control study design with two generations, including four groups: 32 elderly female Holocaust survivors and 47 daughters, and 33 elderly women in the comparison group, and 32 daughters (total N = 174). Participants completed several measures of mental and physical health, and their cognitive functioning was examined. The current study is a follow-up of a previous study conducted 11 years ago with the same participants. Results: Holocaust survivors showed more dissociative symptomatology (odds = 2.39) and less satisfaction with their life (odds = 2.79) as compared to a matched group. Nonetheless, adult offspring of Holocaust survivors showed no differences in their physical, psychological, and cognitive functioning as compared to matched controls. Conclusions: Holocaust survivors still display posttraumatic stress symptoms almost 70 years after the trauma, whereas no intergenerational transmission of trauma was found among the second generation.

Maternal, not paternal, PTSD is related to increased risk for PTSD in offspring of Holocaust survivors

Background A significant association between parental PTSD and the occurrence of PTSD in offspring has been noted, consistent with the idea that risk for the development of PTSD is transmitted from parent to child. Two recent reports linking maternal PTSD and low offspring cortisol prompted us to examine the relative contributions of maternal vs. paternal PTSD in the prediction of PTSD and other psychiatric diagnoses in offspring. Methods One hundred seventeen men and 167 women, recruited from the community, were evaluated using a comprehensive psychiatric battery designed to identify traumatic life experiences and lifetime psychiatric diagnoses. 211 of these subjects were the adult offspring of Holocaust survivors and 73 were demographically comparable Jewish controls. Participants were further subdivided based on whether their mother, father, neither, or both parents met diagnostic criteria for lifetime PTSD. Results A higher prevalence of lifetime PTSD, mood, anxiety disorders, and to a lesser extent, substance abuse disorders, was observed in offspring of Holocaust survivors than controls. The presence of maternal PTSD was specifically associated with PTSD in adult offspring of Holocaust survivors. However, other psychiatric diagnoses did not show specific effects associated with maternal PTSD. Conclusion The tendency for maternal PTSD to make a greater contribution than paternal PTSD to PTSD risk suggests that classic genetic mechanisms are not the sole model of transmission, and paves way for the speculation that epigenetic factors may be involved. In contrast, PTSD in any parent contributes to risk for depression, and parental traumatization is associated with increased anxiety disorders in offspring.

Long-term effects of trauma: Psychosocial functioning of the second and third generation of Holocaust survivors

The long-term effects of extreme war-related trauma on the second and the third generation of Holocaust survivors (HS) were examined in 88 middle-class families. Differences in functioning between adult offspring of HS (HSO) and a comparison group, as well as the psychosocial functioning of adolescent grandchildren of HS, were studied. Degree of presence of Holocaust in the family was examined in families in which both parents were HSO, either mother or father was HSO, and neither parent was HSO. Mothers' Holocaust background was associated with higher levels of psychological distress and less positive parenting representations. In line with synergic (multiplicative) models of risk, adolescents in families where both parents were HSO perceived their mothers as less accepting and less encouraging independence, and reported less positive self-perceptions than their counterparts. They also perceived their fathers as less accepting and less encouraging independence, showed higher levels of ambivalent attachment style, and according to their peers, demonstrated poorer adjustment during military basic training than their fellow recruits from the one-parent HSO group. Parents and adolescents in the one-parent HSO group functioned similarly to others with no Holocaust background. Parenting variables mediated the association across generations between degree of Holocaust experience in the family of origin of the parents and ambivalent attachment style and self-perception of the adolescents. It is recommended that researchers and clinicians develop awareness of the possible traces of trauma in the second and the third generation despite their sound functioning in their daily lives.

Effects of Parental PTSD on the Cortisol Response to Dexamethasone Administration in Their Adult Offspring

Objective: The authors used a low-dose dexamethasone suppression test to examine the effect of a PTSD risk factor, parental PTSD, on cortisol negative feedback inhibition in adult offspring of Holocaust survivors with PTSD (N=13) versus without PTSD (N=12) as well as a comparison group of offspring whose parents had no Holocaust exposure (N=16). Method: Blood samples were obtained at 8:00 a.m. for the determination of baseline cortisol. Participants ingested 0.5 mg of dexamethasone at 11:00 p.m., and blood samples were obtained again at 8:00 a.m. the following day. Results: Enhanced cortisol suppression in response to dexamethasone was associated primarily with parental PTSD status, with minimal contribution of subjects’ own trauma-related symptoms. Conclusions: Enhanced cortisol negative feedback inhibition may be associated with PTSD because it is related to the PTSD risk factor of parental PTSD.

Effects of Parental PTSD on the Cortisol Response to Dexamethasone Administration in Their Adult Offspring

The authors used a low-dose dexamethasone suppression test to examine the effect of a PTSD risk factor, parental PTSD, on cortisol negative feedback inhibition in adult offspring of Holocaust survivors with PTSD (N=13) versus without PTSD (N=12) as well as a comparison group of offspring whose parents had no Holocaust exposure (N=16). Blood samples were obtained at 8:00 a.m. for the determination of baseline cortisol. Participants ingested 0.5 mg of dexamethasone at 11:00 p.m., and blood samples were obtained again at 8:00 a.m. the following day. Enhanced cortisol suppression in response to dexamethasone was associated primarily with parental PTSD status, with minimal contribution of subjects' own trauma-related symptoms. Enhanced cortisol negative feedback inhibition may be associated with PTSD because it is related to the PTSD risk factor of parental PTSD.

Are Adult Offspring Reliable Informants About Parental PTSD? A Validation Study

We developed a short questionnaire--Parental PTSD Questionnaire--(PPQ), designed to assess the presence of posttraumatic stress disorder (PTSD) symptoms in parents. Fifty-eight adult offspring of Holocaust survivors (23 men and 35 women) completed the questionnaire about a parent who was independently evaluated by a trained clinician using the Clinician Administered PTSD Scale (CAPS). Only 5.2% of the offspring reported, "not knowing" if their parent had experienced 10 or fewer symptoms, while 56.9% provided estimates for all 17 items. There were no significant differences between lifetime frequencies of the individual symptoms as endorsed on the PPQ compared to the CAPS when subjects with completed PPQs were compared with CAPS. Interrater reliability between offspring and clinician was highly significant for each of the items when evaluated separately so as to include data for subjects who endorsed not knowing if a certain symptom had been present. Further studies are warranted to examine the psychometric properties of this measure.

Implications of the Holocaust for eating and weight problems among survivors' offspring: an exploratory study

This paper explores the proposition that Holocaust survivors' experiences of deprivation and trauma influenced the development of eating and weight problems among their offspring. Interviews with 11 adult offspring of Holocaust survivors find 10 subjects with current, and one with past, disordered eating. Moreover, eating and/or weight problems are reported for 12 of their 17 siblings. Interviewees' restrained eating syndromes with low weight appear related to parental emigration from Europe by 1941; overeating syndromes with high weight appear related to parental incarceration in concentration camps. By contrast with other studies, in which parents' embracement of the cultural ideal of thinness contributed to their children's development of disordered eating, this study links Holocaust survivors' personal experiences of deprivation and trauma to their offspring's restrained or overeating patterns. Research and clinical implications for the families of war and genocide survivors are discussed. Copyright © 2005 John Wiley & Sons, Ltd and Eating Disorders Association.

Assessing dissociation as a risk factor for posttraumatic stress disorder: a study of adult offspring of holocaust survivors.

Dissociative symptoms are frequently present in trauma survivors with posttraumatic stress disorder (PTSD). However, the possibility that dissociative symptoms may comprise a risk factor for the development of PTSD has not been examined. The current research investigates this possibility by evaluating dissociative symptoms in a group of adult offspring of Holocaust survivors, whom we have previously shown to be at increased risk of PTSD. Eighty-seven Holocaust survivor offspring and 39 comparison participants completed the Dissociative Experiences Scale, and assessments of trauma exposure, psychopathology, and parental PTSD. Dissociative symptoms were elevated in individuals with current PTSD, but not in those with past PTSD or with the risk factor of parental PTSD. Dissociative symptoms were also associated with forms of psychopathology other than PTSD. The results suggest that dissociative symptoms are related to current psychiatric symptomatology, including PTSD, rather than representing an enduring trait or preexisting risk factor for the development of PTSD.

Cortisol levels in adult offspring of Holocaust survivors: relation to PTSD symptom severity in the parent and child.

We have previously demonstrated lower mean 24-h urinary cortisol excretion in adult offspring of Holocaust survivors with parental posttraumatic stress disorder (and lifetime PTSD), compared to offspring without parental PTSD, and to demographically similar comparison subjects. In the current study, we re-analyze data from our previously published report, plus four new subjects, to further examine the relationship between cortisol and severity of PTSD symptoms in offspring and their parents. We also examine the contribution of current depressive disorder to cortisol levels. Two-way analysis of variance revealed lifetime PTSD to be associated with significantly lower cortisol levels, while depressive disorder was associated with higher cortisol levels. The presence of parental PTSD was associated with lower cortisol excretion in the offspring only if both parents were affected. There were significant negative correlations between severity of parental PTSD and offspring urinary cortisol excretion, and between severity of offspring PTSD symptoms and urinary cortisol levels. The findings amplify our earlier descriptions of children of Holocaust survivors with PTSD as a sample 'at risk' for PTSD by demonstrating relationships between lowered cortisol excretion in these offspring and their experience of their parents' PTSD symptoms.

Childhood trauma and risk for PTSD: relationship to intergenerational effects of trauma, parental PTSD, and cortisol excretion.

Among the adverse mental health consequences of childhood trauma is the risk related to the development of posttraumatic stress disorder (PTSD) in adulthood. Other risk factors for PTSD. including parental trauma exposure and parental PTSD, can also contribute to the experience of child trauma. We examined associations between childhood trauma and PTSD in 51 adult children of Holocaust survivors and 41 comparison subjects. in consideration of parental trauma exposure and parental PTSD. We also examined these variables in relation to 24-hr urinary cortisol levels. Adult offspring of Holocaust survivors showed significantly higher levels of self-reported childhood trauma, particularly emotional abuse and neglect. relative to comparison subjects. The difference was largely attributable to parental PTSD. Self-reported childhood trauma was also related to severity of PTSD in subjects, and emotional abuse was significantly associated with 24-hr mean urinary cortisol secretion. We conclude that the experience of childhood trauma may be an important factor in the transmission of PTSD from parent to child.

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

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 (55 men and 80 women) were divided into three groups according to parental trauma exposure and PTSD: 60 subjects were offspring of Holocaust survivors who endorsed having at least one parent with PTSD, 33 were offspring of Holocaust survivors who reported having 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 traumatic events was obtained. Subjects also completed a checklist based on the 17 DSM-IV symptoms of PTSD, to estimate the symptom 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, parental PTSD, and the subject's own history of trauma in the development of PTSD, depressive, and anxiety disorders in the offspring. The findings 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 identification of parental PTSD as a risk factor for PTSD in offspring of Holocaust survivors defines a sample in which the biological and psychological correlates of risk for PTSD can be further examined.

Low Cortisol and Risk for PTSD in Adult Offspring of Holocaust Survivors

The study examined the association between cortisol and putative risk factors for posttraumatic stress disorder (PTSD) in a sample of subjects at increased risk for the development of PTSD. Twenty-four-hour urinary cortisol excretion was measured in 35 adult offspring of Holocaust survivors and 15 healthy comparison subjects who were not offspring of Holocaust survivors. Subjects were also characterized with regard to clinical symptoms, presence or absence of psychiatric diagnoses including PTSD, and presence or absence of PTSD in their parents. Low cortisol levels were significantly associated with both PTSD in parents and lifetime PTSD in subjects, whereas having a current psychiatric diagnosis other than PTSD was relatively, but nonsignificantly, associated with higher cortisol levels. Offspring with both parental PTSD and lifetime PTSD had the lowest cortisol levels of all study groups. Parental PTSD, a putative risk factor for PTSD, appears to be associated with low cortisol levels in offspring, even in the absence of lifetime PTSD in the offspring. The findings suggest that low cortisol levels in PTSD may constitute a vulnerability marker related to parental PTSD as well as a state-related characteristic associated with acute or chronic PTSD symptoms.

Vulnerability to posttraumatic stress disorder in adult offspring of Holocaust survivors.

There has been considerable controversy regarding the impact of the Holocaust on the second generation, but few empirical data are available that systematically document trauma exposure and psychiatric disorder in these individuals. To obtain such data, the authors examined the prevalence of stress and exposure to trauma, current and lifetime posttraumatic stress disorder (PTSD), and other psychiatric diagnoses in a group of adult offspring of Holocaust survivors (N=100) and a demographically similar comparison group (N=44). Subjects were recruited from both community and clinical populations and were evaluated with the use of structured clinical instruments. Stress and trauma history were evaluated with the Antonovsky Life Crises Scale and the Trauma History Questionnaire, PTSD was diagnosed with the Clinician Administered PTSD Scale, and other psychiatric disorders were evaluated according to the Structured Clinical Interview for DSM-IV. The data show that although adult offspring of Holocaust survivors did not experience more traumatic events, they had a greater prevalence of current and lifetime PTSD and other psychiatric diagnoses than the demographically similar comparison subjects. This was true in both community and clinical subjects. The findings demonstrate an increased vulnerability to PTSD and other psychiatric disorders among offspring of Holocaust survivors, thus identifying adult offspring as a possible high-risk group within which to explore the individual differences that constitute risk factors for PTSD.