Karestan C. Koenen

Biological studies of post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is the only major mental disorder for which a cause is considered to be known: that is, an event that involves threat to the physical integrity of oneself or others and induces a response of intense fear, helplessness or horror. Although PTSD is still largely regarded as a psychological phenomenon, over the past three decades the growth of the biological PTSD literature has been explosive, and thousands of references now exist. Ultimately, the impact of an environmental event, such as a psychological trauma, must be understood at organic, cellular and molecular levels. This Review attempts to present the current state of this understanding on the basis of psychophysiological, structural and functional neuroimaging, and endocrinological, genetic and molecular biological studies in humans and in animal models.

Race/ethnic differences in exposure to traumatic events, development of post-traumatic stress disorder, and treatment-seeking for post-traumatic stress disorder in the United States

BACKGROUND To identify sources of race/ethnic differences related to post-traumatic stress disorder (PTSD), we compared trauma exposure, risk for PTSD among those exposed to trauma, and treatment-seeking among Whites, Blacks, Hispanics and Asians in the US general population. METHOD Data from structured diagnostic interviews with 34 653 adult respondents to the 2004-2005 wave of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were analysed. RESULTS The lifetime prevalence of PTSD was highest among Blacks (8.7%), intermediate among Hispanics and Whites (7.0% and 7.4%) and lowest among Asians (4.0%). Differences in risk for trauma varied by type of event. Whites were more likely than the other groups to have any trauma, to learn of a trauma to someone close, and to learn of an unexpected death, but Blacks and Hispanics had higher risk of child maltreatment, chiefly witnessing domestic violence, and Asians, Black men, and Hispanic women had higher risk of war-related events than Whites. Among those exposed to trauma, PTSD risk was slightly higher among Blacks [adjusted odds ratio (aOR) 1.22] and lower among Asians (aOR 0.67) compared with Whites, after adjustment for characteristics of trauma exposure. All minority groups were less likely to seek treatment for PTSD than Whites (aOR range: 0.39-0.61), and fewer than half of minorities with PTSD sought treatment (range: 32.7-42.0%). CONCLUSIONS When PTSD affects US race/ethnic minorities, it is usually untreated. Large disparities in treatment indicate a need for investment in accessible and culturally sensitive treatment options.

Research Review: DSM-V Conduct Disorder--Research Needs for an Evidence Base.

This article charts a strategic research course toward an empirical foundation for the diagnosis of conduct disorder in the forthcoming DSM-V. Since the DSM-IV appeared in 1994, an impressive amount of new information about conduct disorder has emerged. As a result of this new knowledge, reasonable rationales have been put forward for adding to the conduct disorder diagnostic protocol: a childhood-limited subtype, family psychiatric history, callous-unemotional traits, female-specific criteria, preschool-specific criteria, early substance use, and biomarkers from genetics, neuroimaging, and physiology research. This article reviews the evidence for these and other potential changes to the conduct disorder diagnosis. We report that although there is a great deal of exciting research into each of the topics, very little of it provides the precise sort of evidence base required to justify any alteration to the DSM-V. We outline specific research questions and study designs needed to build the lacking evidence base for or against proposed changes to DSM-V conduct disorder.

Epigenetic and immune function profiles associated with posttraumatic stress disorder

The biologic underpinnings of posttraumatic stress disorder (PTSD) have not been fully elucidated. Previous work suggests that alterations in the immune system are characteristic of the disorder. Identifying the biologic mechanisms by which such alterations occur could provide fundamental insights into the etiology and treatment of PTSD. Here we identify specific epigenetic profiles underlying immune system changes associated with PTSD. Using blood samples (n = 100) obtained from an ongoing, prospective epidemiologic study in Detroit, the Detroit Neighborhood Health Study, we applied methylation microarrays to assay CpG sites from more than 14,000 genes among 23 PTSD-affected and 77 PTSD-unaffected individuals. We show that immune system functions are significantly overrepresented among the annotations associated with genes uniquely unmethylated among those with PTSD. We further demonstrate that genes whose methylation levels are significantly and negatively correlated with traumatic burden show a similar strong signal of immune function among the PTSD affected. The observed epigenetic variability in immune function by PTSD is corroborated using an independent biologic marker of immune response to infection, CMV—a typically latent herpesvirus whose activity was significantly higher among those with PTSD. This report of peripheral epigenomic and CMV profiles associated with mental illness suggests a biologic model of PTSD etiology in which an externally experienced traumatic event induces downstream alterations in immune function by reducing methylation levels of immune-related genes.

Childhood IQ and adult mental disorders: a test of the cognitive reserve hypothesis.

OBJECTIVE Cognitive reserve has been proposed as important in the etiology of neuropsychiatric disorders. However, tests of the association between premorbid IQ and adult mental disorders other than schizophrenia have been limited and inconclusive. The authors tested the hypothesis that low childhood IQ is associated with increased risk and severity of adult mental disorders. METHOD Participants were members of a representative 1972-1973 birth cohort of 1,037 males and females in Dunedin, New Zealand, who were followed up to age 32 with 96% retention. WISC-R IQ was assessed at ages 7, 9, and 11. Research diagnoses of DSM mental disorders were made at ages 18, 21, 26, and 32. RESULTS Lower childhood IQ was associated with increased risk of developing schizophrenia spectrum disorder, adult depression, and adult anxiety. Lower childhood IQ was also associated with greater comorbidity and with persistence of depression; the association with persistence of generalized anxiety disorder was nearly significant. Higher childhood IQ predicted increased risk of adult mania. CONCLUSIONS Lower cognitive reserve, as reflected by childhood IQ, is an antecedent of several common psychiatric disorders and also predicts persistence and comorbidity. Thus, many patients who seek mental health treatment may have lower cognitive ability; this should be considered in prevention and treatment planning.

Early childhood factors associated with the development of post-traumatic stress disorder: results from a longitudinal birth cohort

BACKGROUND Childhood factors have been associated with increased risk of developing post-traumatic stress disorder (PTSD). Previous studies assessed only a limited number of childhood factors retrospectively. We examined the association between childhood neurodevelopmental, temperamental, behavioral and family environmental characteristics assessed before age 11 years and the development of PTSD up to age 32 years in a birth cohort. METHOD Members of a 1972-73 New Zealand birth cohort (n=1037) who were assessed at ages 26 and 32 years for PTSD as defined by DSM-IV. RESULTS We identified two sets of childhood risk factors. The first set of risk factors was associated both with increased risk of trauma exposure and with PTSD assessed at age 26. These included childhood externalizing characteristics and family environmental stressors, specifically maternal distress and loss of a parent. The second set of risk factors affected risk for PTSD only and included low IQ and chronic environmental adversity. The effect of cumulative childhood factors on risk of PTSD at age 26 was substantial; over 58% of cohort members in the highest risk quartile for three developmental factors had PTSD as compared to only 25% of those not at high risk on any factors. Low IQ at age 5, antisocial behavior, and poverty before age 11 continued to predict PTSD related to traumatic events that occurred between the ages of 26 and 32. CONCLUSIONS Developmental capacities and conditions of early childhood may increase both risk of trauma exposure and the risk that individuals will respond adversely to traumatic exposures. Rather than being solely a response to trauma, PTSD may have developmental origins.

Domestic violence is associated with environmental suppression of IQ in young children

Research suggests that exposure to extreme stress in childhood, such as domestic violence, affects childrens neurocognitive development, leading to lower intelligence. But studies have been unable to account for genetic influences that might confound the association between domestic violence and lower intelligence. This twin study tested whether domestic violence had environmentally mediated effects on young childrens intelligence. Childrens IQs were assessed for a population sample of 1116 monozygotic and dizygotic 5-year-old twin pairs in England. Mothers reported their experience of domestic violence in the previous 5 years. Ordinary least squares regression showed that domestic violence was uniquely associated with IQ suppression in a dose-response relationship. Children exposed to high levels of domestic violence had IQs that were, on average, 8 points lower than unexposed children. Structural equation models showed that adult domestic violence accounted for 4% of the variation, on average, in child IQ, independent of latent genetic influences. The findings are consistent with animal experiments and human correlational studies documenting the harmful effects of extreme stress on brain development Programs that successfully reduce domestic violence should also have beneficial effects on childrens cognitive development.

Risk factors for course of posttraumatic stress disorder among Vietnam veterans: a 14-year follow-up of American Legionnaires.

Risk factors affecting the course of posttraumatic stress disorder (PTSD) are poorly understood. As part of a larger study on characterizing exposure to herbicides in Vietnam, the authors investigated this issue in a random sample of 1,377 American Legionnaires who had served in Southeast Asia during the Vietnam War and were followed over a 14-year period. High combat exposure, perceived negative community attitudes at homecoming, minority race, depression symptoms at Time 1, and more anger at Time 1 predicted a more chronic course. Community involvement at Time 1 was protective and associated with decreased risk at Time 2. Discomfort in disclosing Vietnam experiences was associated with an increased risk for developing PTSD but did not predict its course. Combat exposure predicted PTSD course more strongly than any other risk factor. Findings suggest recovery from PTSD is significantly influenced by perceived social support.

Childhood Sexual Abuse Is Highly Associated With HIV Risk-Taking Behavior and Infection Among MSM in the EXPLORE Study

Background:Previous studies have found high rates of childhood sexual abuse (CSA) among US men who have sex with men (MSM). CSA history has been associated with a variety of negative effects later in life including behaviors that place MSM at greater risk for HIV acquisition and transmission. The present analysis is the first to examine the longitudinal association between CSA and HIV infection, unprotected anal sex, and serodiscordant unprotected anal sex, as well as mediators of these relationships among a large sample of HIV-uninfected MSM. Methods:The EXPLORE Study was a behavioral intervention trial conducted in 6 US cities over 48 months with HIV infection as the primary efficacy outcome. Behavioral assessments were done every 6 months via confidential computerized assessments. Longitudinal regression models were constructed, adjusting for randomization arm, geographical location of study site, age at enrollment, education, and race/ethnicity. Results:Of the 4295 participants enrolled, 39.7% had a history of CSA. Participants with a history of CSA [adjusted hazards ratio = 1.30, 95% confidence interval (CI): 1.02 to 1.69] were at increased risk for HIV infection over study follow-up. A significant association was seen between history of CSA and unprotected anal sex (adjusted odds ratio = 1.24, 95% CI: 1.12 to 1.36) and serodiscordant unprotected anal sex (adjusted odds ratio = 1.30, 95% CI: 1.18 to 1.43). Among participants reporting CSA, the EXPLORE intervention had no effect in reducing HIV infection rates. Participants reporting CSA were significantly more likely to have symptoms of depression and use nonprescription drugs. Conclusions:A predictive relationship between a history of CSA and subsequent HIV infection was observed among this large sample of HIV-uninfected MSM. Findings indicate that HIV-uninfected MSM with CSA histories are at greater risk for HIV infection, report higher rates of HIV sexual risk behavior, and may derive less benefit from prevention programs. Future HIV prevention interventions should address the specific mental health concerns of MSM with a history of CSA.

A twin registry study of familial and individual risk factors for trauma exposure and posttraumatic stress disorder

This study examines the association of individual and familial risk factors with exposure to trauma and posttraumatic stress disorder (PTSD) in male twins (N = 6744) from the Vietnam Era Twin Registry. Independent reports of familial psychopathology from co-twins were used to avoid the potential biases of the family history method. Risk for exposure to traumatic events was increased by service in Southeast Asia, preexisting conduct disorder, preexisting substance dependence, and a family history of mood disorders whose effects appear to be partly genetic. Preexisting mood disorders in the individual were associated with decreased odds of traumatic exposure. Risk of developing PTSD following exposure was increased by an earlier age at first trauma, exposure to multiple traumas, paternal depression, less than high school education at entry into the military, service in Southeast Asia, and preexisting conduct disorder, panic disorder or generalized anxiety disorder, and major depression. Results suggest the association of familial psychopathology and PTSD may be mediated by increased risk of traumatic exposure and by preexisting psychopathology.