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.

Discounting future outcomes as a function of their deferred availability underlies much of human decision making. Discounting, or preference for immediate over delayed rewards of larger value, is often associated with impulsivity and is a risk factor for addictive disorders such as pathological gambling, cigarette smoking, and drug and alcohol abuse. The ventral striatum (VS) is involved in mediating behavioral responses and physiological states associated with reward, and dysregulation of the VS contributes to addiction, perhaps by affecting impulsive decision-making. Behavioral tests of delay discounting (DD), which index preference for smaller immediate over larger delayed rewards, covary with impulsive tendencies in humans. In the current study, we examined the relationship between individual differences in DD, measured in a behavioral assessment, and VS activity measured with blood oxygenation leveldependent functional magnetic resonance imaging, in 45 adult volunteers. VS activity was determined using a task involving positive and negative feedback with monetary reward. Analyses revealed that individual differences in DD correlate positively with magnitude of VS activation in response to both positive and negative feedback, compared with a no-feedback control condition. Variability in DD was also associated with differential VS activation in response to positive, compared with negative, feedback. Collectively, our results suggest that increased preference for smaller immediate over larger delayed rewards reflects both a relatively indiscriminate and hyper-reactive VS circuitry. They also highlight a specific neurocognitive mechanism that may contribute to increased risk for addiction.

These data suggest that sleep duration is a significant correlate of the metabolic syndrome. Additional studies are needed to evaluate temporal relationships among these measures, the behavioral and physiologic mechanisms that link the two, and their impact on subsequent cardiometabolic disease.

It is now widely acknowledged that the personal burden of illness cannot be described fully by measures of disease status such as size of infarction, tumour load, and forced expiratory volume. Psychosocial factors such as pain, apprehension, restricted mobility and other functional impairments, difficulty fulfilling personal and family responsibilities, financial burden, and diminished cognition must also be encompassed. The area of research that has resulted from this recognition is termed "health related quality of life." It moves beyond direct manifestations of illness to study the patient's personal morbidity-that is, the various effects that illnesses and treatments have on daily life and life satisfaction. Although quality of life assessment was almost unknown 15 years ago, it has rapidly become an integral variable of outcome in clinical research; over 1000 new articles each year are indexed under "quality of life."Although the importance of quality of life is broadly acknowledged, scepticism and confusion remain about how quality of life should be measured and its usefulness in medical research. These responses may reflect important conceptual and methodological limitations of the current concept of quality of life. We offer a simple framework that describes the core elements of quality of life related to health and use this to evaluate quality of life measurement as it is currently conducted.

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