Preface Posttraumatic stress disorder (PTSD) is the only major mental disorder for which a cause is considered to be known, viz., 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. The present review attempts to present the current state of this understanding, based upon psychophysiological, structural and functional neuroimaging, endocrinological, genetic, and molecular biological studies in humans and in animal models.

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.

Background: Although post-traumatic stress disorder (PTSD) onset-persistence is thought to vary significantly by trauma type, most epidemiological surveys are incapable of assessing this because they evaluate lifetime PTSD only for traumas nominated by respondents as their ‘worst.’ Objective: To review research on associations of trauma type with PTSD in the WHO World Mental Health (WMH) surveys, a series of epidemiological surveys that obtained representative data on trauma-specific PTSD. Method: WMH Surveys in 24 countries (n = 68,894) assessed 29 lifetime traumas and evaluated PTSD twice for each respondent: once for the ‘worst’ lifetime trauma and separately for a randomly-selected trauma with weighting to adjust for individual differences in trauma exposures. PTSD onset-persistence was evaluated with the WHO Composite International Diagnostic Interview. Results: In total, 70.4% of respondents experienced lifetime traumas, with exposure averaging 3.2 traumas per capita. Substantial between-trauma differences were found in PTSD onset but less in persistence. Traumas involving interpersonal violence had highest risk. Burden of PTSD, determined by multiplying trauma prevalence by trauma-specific PTSD risk and persistence, was 77.7 person-years/100 respondents. The trauma types with highest proportions of this burden were rape (13.1%), other sexual assault (15.1%), being stalked (9.8%), and unexpected death of a loved one (11.6%). The first three of these four represent relatively uncommon traumas with high PTSD risk and the last a very common trauma with low PTSD risk. The broad category of intimate partner sexual violence accounted for nearly 42.7% of all person-years with PTSD. Prior trauma history predicted both future trauma exposure and future PTSD risk. Conclusions: Trauma exposure is common throughout the world, unequally distributed, and differential across trauma types with respect to PTSD risk. Although a substantial minority of PTSD cases remits within months after onset, mean symptom duration is considerably longer than previously recognized.

BACKGROUND-Childhood adversity is associated with adult mental disorders, but the mechanisms underlying this association remain inadequately understood. Stress sensitization, whereby childhood adversity increases vulnerability to mental disorders following adult stressful life events, has been proposed as a potential mechanism. We provide a test of the stress sensitization hypothesis in a national sample.

Objective Although exposure to potentially traumatic experiences (PTEs) is common among US youths, information on posttraumatic stress disorder (PTSD) risk associated with PTEs is limited. We estimate lifetime prevalence of exposure to PTEs and PTSD, PTE-specific risk of PTSD, and associations of sociodemographics and temporally-prior DSM-IV disorders with PTE exposure, PTSD given exposure, and PTSD recovery among US adolescents. Method Data were drawn from 6,483 adolescent–parent pairs in the National Comorbidity Survey Replication Adolescent Supplement (NCS-A), a national survey of adolescents aged 13–17. Lifetime exposure to interpersonal violence, accidents/injuries, network/witnessing, and other PTEs was assessed along with DSM-IV PTSD and other distress, fear, behavior, and substance disorders. Results A majority (61.8%) of adolescents experienced a lifetime PTE. Lifetime prevalence of DSM-IV PTSD was 4.7% and was significantly higher among females (7.3%) than males (2.2%). Exposure to PTEs, particularly interpersonal violence, was highest among adolescents not living with both biological parents and with pre-existing behavior disorders. Conditional probability of PTSD was highest for PTEs involving interpersonal violence. Predictors of PTSD among PTE-exposed adolescents included female gender, prior PTE exposure, and pre-existing fear and distress disorders. One-third (33.0%) of adolescents with lifetime PTSD continued to meet criteria within 30 days of interview. Poverty, U.S. nativity, bipolar disorder, and PTE exposure occurring after the focal trauma predicted nonrecovery. Conclusions Interventions designed to prevent PTSD in PTE-exposed youths should be targeted at victims of interpersonal violence with pre-existing fear and distress disorders, whereas interventions designed to reduce PTSD chronicity should attempt to prevent secondary PTE exposure.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

In 1988, the National Vietnam Veterans Readjustment Study (NVVRS) of a representative sample of 1200 veterans estimated that 30.9% had developed posttraumatic stress disorder (PTSD) during their lifetimes and that 15.2% were currently suffering from PTSD. The study also found a strong dose-response relationship: As retrospective reports of combat exposure increased, PTSD occurrence increased. Skeptics have argued that these results are inflated by recall bias and other flaws. We used military records to construct a new exposure measure and to cross-check exposure reports in diagnoses of 260 NVVRS veterans. We found little evidence of falsification, an even stronger doseresponse relationship, and psychological costs that were lower than previously estimated but still substantial. According to our fully adjusted PTSD rates, 18.7% of the veterans had developed warrelated PTSD during their lifetimes and 9.1% were currently suffering from PTSD 11 to 12 years after the war; current PTSD was typically associated with moderate impairment.

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.Cognitive reserve has been proposed as an important etiologic factor in the development and severity of neuropsychiatric disorders (1). The construct of cognitive reserve refers to individual differences in brain structure (e.g., density of neuronal synapses) and function (e.g., processing efficiency) thought to buffer the effects of neuropathology. Evidence has emerged from the rapidly evolving field of cognitive epidemiology (2) showing that IQ, a marker of cognitive reserve, is inversely related to risk of total psychiatric illness (3). However, with the exception of research on schizophrenia (4), surprisingly few studies have examined the relation Correspondence to: Karestan C. Koenen.Address correspondence and reprint requests to Dr. Koenen, Department of Society, Human Development, and Health, Harvard School of Public Health, Kresge 613, 677 Huntington Ave., Boston, MA 02115; E-mail: kkoenen@hsph.harvard.edu (e-mail). The authors report no competing interests. NIH Public Access Author ManuscriptAm J Psychiatry. Author manuscript; available in PMC 2010 January 1. between IQ early in life and the risk of other specific adult psychiatric disorders. Among those studies that have examined other disorders, the results have been inconclusive. We report a longitudinal study of the 20-year predictive association between childhood IQ and adult mental disorders among members of the Dunedin, New Zealand, birth cohort.In the earlier studies, low IQ at military entry increased the risk of hospitalization for depression in male Swedish conscripts (5) but not male Danish conscripts (6). Studies of bipolar disorder have largely shown no associa...