Maternal Exposure to the Holocaust and Health Complaints in Offspring

Although the link between chronic stress and the development of cardiovascular and metabolic diseases of adulthood has been known for some time, there is growing recognition that early environmental influences may result in developmental programming via epigenetic mechanisms, thereby affecting the developmental trajectory of disease progression. Previous studies support the idea that offspring of Holocaust survivors may have been subjected to early developmental programming. We evaluated the relationship between parental exposure to the Holocaust and selfreported health ratings and disorders made by their adult offspring (i.e., second generation Holocaust survivors). A total of 137 subjects were evaluated. Regression analyses demonstrated that maternal but not paternal exposure to the Holocaust was related to poorer subjective impressions of emotional and physical health. This relationship was diminished when the offspring’s own level of trait anxiety was considered. Offspring with maternal, but not paternal, Holocaust exposure also reported greater use of psychotropic and other medications, including medications for the treatment of hypertension and lipid disorders. The mechanism linking these health outcomes and maternal exposure deserves further investigation, including the possibility that fetal or early developmental programming is involved

The Role of Genes in Defining a Molecular Biology of PTSD

Because environmental exposure to trauma is the sine qua non for the development of Post Traumatic Stress Disorder (PTSD), the recent focus on genetic studies has been noteworthy. The main catalyst for such studies is the observation from epidemiological studies that not all trauma survivors develop this disorder. Furthermore, neuroendocrine findings suggest pre-existing hormonal alterations that confer risk for PTSD. This paper presents the rationale for examining genetic factors in PTSD and trauma exposure, but suggests that studies of genotype may only present a limited picture of the molecular biology of this disorder. We describe the type of information that can be obtained from candidate gene and genomic studies that incorporate environmental factors in the design (i.e., gene – environment interaction and gene-environment correlation studies) and studies that capitalize on the idea that environment modifies gene expression, via epigenetic or other molecular mechanisms. The examination of epigenetic mechanisms in tandem with gene expression will help refine models that explain how PTSD risk, pathophysiology, and recovery is mediated by the environment. Since inherited genetic variation may also influence the extent of epigenetic or gene expression changes resulting from the environment, such studies should optimally be followed up by studies of genotype

Joint Effect of Childhood Abuse and Family History of Major Depressive Disorder on Rates of PTSD in People with Personality Disorders

Objective. Childhood maltreatment and familial psychopathology both lead to an increased risk of the development of posttraumatic stress disorder (PTSD) in adulthood. While family history of psychopathology has traditionally been viewed as a proxy for genetic predisposition, such pathology can also contribute to a stress-laden environment for the child. Method. Analyses were conducted to evaluate the joint effect of childhood abuse and a family history of major depressive disorder (MDD) on diagnoses of PTSD and MDD in a sample of 225 adults with DSM-IV Axis II disorders. Results. Results showed that the rate of PTSD in the presence of both childhood abuse and MDD family history was almost six-fold (OR = 5.89, P = .001) higher relative to the absence of both factors. In contrast, the rate of MDD in the presence of both factors was associated with a nearly three-fold risk relative to the reference group (OR = 2.75, P = .01). Conclusions. The results from this observational study contribute to a growing understanding of predisposing factors for the development of PTSD and suggest that joint effects of family history of MDD and childhood abuse on PTSD are greater than either factor alone

Hostile mood and social strain during daily life: A test of the transactional model.

Hostility is a multidimensional construct related to cardiovascular (CV) disease risk. Daily hostile mood and social interactions may precipitate stress-related CV responses in hostile individuals. Purpose: Determine whether trait cognitive hostility best predicts daily hostile mood and social interactions relative to other trait hostility factors and explore the temporal links between these daily measure

Maternal exposure to the holocaust and health complaints in offspring

Abstract. Although the link between chronic stress and the development of cardiovascular and metabolic diseases of adulthood has been known for some time, there is growing recognition that early environmental influences may result in developmental programming via epigenetic mechanisms, thereby affecting the developmental trajectory of disease progression. Previous studies support the idea that offspring of Holocaust survivors may have been subjected to early developmental programming. We evaluated the relationship between parental exposure to the Holocaust and self-reported health ratings and disorders made by their adult offspring (i.e., second generation Holocaust survivors). A total of 137 subjects were evaluated. Regression analyses demonstrated that maternal but not paternal exposure to the Holocaust was related to poorer subjective impressions of emotional and physical health. This relationship was diminished when the offspring's own level of trait anxiety was considered. Offspring with maternal, but not paternal, Holocaust exposure also reported greater use of psychotropic and other medications, including medications for the treatment of hypertension and lipid disorders. The mechanism linking these health outcomes and maternal exposure deserves further investigation, including the possibility that fetal or early developmental programming is involved

Polygenic risk associated with post-traumatic stress disorder onset and severity.

Post-traumatic stress disorder (PTSD) is a psychiatric illness with a highly polygenic architecture without large effect-size common single-nucleotide polymorphisms (SNPs). Thus, to capture a substantial portion of the genetic contribution, effects from many variants need to be aggregated. We investigated various aspects of one such approach that has been successfully applied to many traits, polygenic risk score (PRS) for PTSD. Theoretical analyses indicate the potential prediction ability of PRS. We used the latest summary statistics from the largest published genome-wide association study (GWAS) conducted by Psychiatric Genomics Consortium for PTSD (PGC-PTSD). We found that the PRS constructed for a cohort comprising veterans of recent wars (n = 244) explains a considerable proportion of PTSD onset (Nagelkerke R2 = 4.68%, P = 0.003) and severity (R2 = 4.35%, P = 0.0008) variances. However, the performance on an African ancestry sub-cohort was minimal. A PRS constructed with schizophrenia GWAS also explained a significant fraction of PTSD diagnosis variance (Nagelkerke R2 = 2.96%, P = 0.0175), confirming previously reported genetic correlation between the two psychiatric ailments. Overall, these findings demonstrate the important role polygenic analyses of PTSD will play in risk prediction models as well as in elucidating the biology of the disorder

Joint Effect of Childhood Abuse and Family History of Major Depressive Disorder on Rates of PTSD in People with Personality Disorders

Objective. Childhood maltreatment and familial psychopathology both lead to an increased risk of the development of posttraumatic stress disorder (PTSD) in adulthood. While family history of psychopathology has traditionally been viewed as a proxy for genetic predisposition, such pathology can also contribute to a stress-laden environment for the child. Method. Analyses were conducted to evaluate the joint effect of childhood abuse and a family history of major depressive disorder (MDD) on diagnoses of PTSD and MDD in a sample of 225 adults with DSM-IV Axis II disorders. Results. Results showed that the rate of PTSD in the presence of both childhood abuse and MDD family history was almost six-fold (OR = 5.89, P = .001) higher relative to the absence of both factors. In contrast, the rate of MDD in the presence of both factors was associated with a nearly three-fold risk relative to the reference group (OR = 2.75, P = .01). Conclusions. The results from this observational study contribute to a growing understanding of predisposing factors for the development of PTSD and suggest that joint effects of family history of MDD and childhood abuse on PTSD are greater than either factor alone

Post-Traumatic Stress Disorder and Cardiovascular Diseases: A Cohort Study of Men and Women Involved in Cleaning the Debris of the World Trade Center Complex

BACKGROUND: To determine whether post-traumatic stress disorder (PTSD) is a risk factor for myocardial infarction (MI) and stroke, beyond the expected effects from recognized cardiovascular risk factors and depression. METHODS AND RESULTS: World Trade Center-Heart is an observational prospective cohort study of 6481 blue-collar first responders nested within the World Trade Center Health Program in New York City. Baseline measures in 2012 and 2013 included blood pressure, weight and height, and blood lipids. PTSD, depression, smoking, and dust exposure during the 2001 cleanup were self-reported. During the 4-year follow-up, outcomes were assessed through (1) interview-based incident, nonfatal MI, and stroke, validated in medical charts (n=118); and (2) hospitalizations for MI and stroke for New York city and state residents (n=180). Prevalence of PTSD was 19.9% in men and 25.9% in women, that is, at least twice that of the general population. Cumulative incidence of MI or stroke was consistently larger for men or women with PTSD across follow-up. Adjusted hazard ratios (HRs) were 2.22 (95% confidence interval [CI], 1.30–3.82) for MI and 2.51 (95% CI, 1.39–4.57) for stroke. For pooled MI and stroke, adjusted HRs were 2.35 (95% CI, 1.57–3.52) in all and 1.88 (95% CI, 1.01–3.49) in men free of depression. Using hospitalization registry data, adjusted HRs were 2.17 (95% CI, 1.41–3.32) for MI; 3.01 (95% CI, 1.84–4.93) for stroke; and for pooled MI and stroke, the adjusted HR was 2.40 (95% CI, 1.73–3.34) in all, HR was 2.44 (95% CI, 1.05–5.55) in women, and adjusted HR was 2.27 (95% CI, 1.41–3.67) in men free of depression. World Trade Center dust exposure had no effect. CONCLUSIONS: This cohort study confirms that PTSD is a risk factor for MI and stroke of similar magnitude in men and women, independent of depression

Perigenual anterior cingulate morphology covaries with perceived social standing

Low socioeconomic status (SES) increases the risk for developing psychiatric and chronic medical disorders. A stress-related pathway by which low SES may affect mental and physical health is through the perception of holding a low social standing, termed low subjective social status. This proposal implicates overlapping brain regions mediating stress reactivity and socioemotional behaviors as neuroanatomical substrates that could plausibly link subjective social status to health-related outcomes. In a test of this proposal, we used a computational structural neuroimaging method (voxel-based morphometry) in a healthy community sample to examine the relationships between reports of subjective social status and regional gray matter volume. Results showed that after accounting for potential demographic confounds, subclinical depressive symptoms, dispositional forms of negative emotionality and conventional indicators of SES, self-reports of low subjective social status uniquely covaried with reduced gray matter volume in the perigenual area of the anterior cingulate cortex (pACC)—a brain region involved in experiencing emotions and regulating behavioral and physiological reactivity to psychosocial stress. The pACC may represent a neuroanatomical substrate by which perceived social standing relates to mental and physical health

Distinct Profiles of Cell-Free MicroRNAs in Plasma of Veterans with Post-Traumatic Stress Disorder.

Dysregulation of circulating microRNAs (miRNAs) in body fluids has been reported in psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, and post-traumatic stress disorder (PTSD). Recent studies of various diseases showed that extracellular vesicles (EV) in body fluids can provide different spectra of circulating miRNAs and disease-associated signatures from whole fluid or EV-depleted fraction. However, the association of miRNAs in EVs to PTSD has not been studied. In this study, we performed a comprehensive profiling of miRNAs in whole plasma, extracellular vesicles (EV) and EV-depleted plasma (EVD) samples collected from combat veterans with PTSD and matched controls by utilizing a next-generation sequencing (NGS) platform. In total, 520 circulating miRNAs were quantified from 24 male Iraq and Afghanistan combat veterans with