ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry.

A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American case-control studies in which alcohol dependence was defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and demonstrated a strong protective effect of the His48 variant (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.24, 0.48) on alcohol dependence, with genome-wide significance (6.6 × 10(-10)). The hypothesized mechanism of action involves an increased aversive reaction to alcohol; in keeping with this hypothesis, the same allele is strongly associated with a lower maximum number of drinks in a 24-hour period (lifetime), with P=3 × 10(-13). We also tested the effects of this allele on the development of alcoholism in adolescents and young adults, and demonstrated a significantly protective effect. This variant has the strongest effect on risk for alcohol dependence compared with any other tested variant in European populations

Model for Incomplete Reconnection in Sawtooth Crashes

A model for incomplete reconnection in sawtooth crashes is presented. The reconnection inflow during the crash phase of sawteeth self-consistently convects the high pressure core toward the reconnection site, raising the pressure gradient there. Reconnection shuts off if the diamagnetic drift speed at the reconnection site exceeds a threshold, which may explain incomplete reconnection. The relaxation of magnetic shear after reconnection stops may explain the destabilization of ideal interchange instabilities reported previously. Proof-of-principle two-fluid simulations confirm this basic picture. Predictions of the model compare favorably to data from the Mega Ampere Spherical Tokamak. Applications to transport modeling of sawteeth are discussed. The results should apply across tokamaks, including ITER.Comment: 5 pages, 3 figures, accepted for publication in PR

The neurobiological basis of sex differences in learned fear and its inhibition

Learning that certain cues or environments predict threat enhances survival by promoting appropriate fear and the resulting defensive responses. Adapting to changing stimulus contingencies by learning that such cues no longer predict threat, or distinguishing between these threat‐related and other innocuous stimuli, also enhances survival by limiting fear responding in an appropriate manner to conserve resources. Importantly, a failure to inhibit fear in response to harmless stimuli is a feature of certain anxiety and trauma‐related disorders, which are also associated with dysfunction of the neural circuitry underlying learned fear and its inhibition. Interestingly, these disorders are up to twice as common in women, compared to men. Despite this striking sex difference in disease prevalence, the neurobiological factors involved remain poorly understood. This is due in part to the majority of relevant preclinical studies having neglected to include female subjects alongside males, which has greatly hindered progress in this field. However, more recent studies have begun to redress this imbalance and emerging evidence indicates that there are significant sex differences in the inhibition of learned fear and associated neural circuit function. This paper provides a narrative review on sex differences in learned fear and its inhibition through extinction and discrimination, along with the key gonadal hormone and brain mechanisms involved. Understanding the endocrine and neural basis of sex differences in learned fear inhibition may lead to novel insights on the neurobiological mechanisms underlying the enhanced vulnerability to develop anxiety‐related disorders that are observed in women

Empowerment and the Transition to Housing for Homeless Mentally Ill People: An Anthropological Perspective

Often lacking in scholarly and policy-oriented discussions of homelessness are contextualized understandings of the problems faced, and the values held, by homeless mentally ill people. This article, using an anthropological perspective, examines issues that arise for homeless mentally ill individuals in making the transition from shelter living to permanent residences. The transition occurs as part of a housing initiative driven by the philosophy of consumer empowerment. Project participants are placed in independent apartments or evolving consumer households (ECH) — shared, staffed residences designed to transform themselves into consumer-directed living situations over time. The effects of an empowerment paradigm on the organization of space, the nature of social relations, and the management of economic resources in the ECHs are discussed to show that consumers and staff sometimes have contrasting views of what empowerment entails. It is suggested that anthropological research can help to illuminate the issues at stake in determining policy for homeless people with major mental illness

Smoking cessation is associated with lower rates of mood/anxiety and alcohol use disorders

BACKGROUND: The psychological outcomes that accompany smoking cessation are not yet conclusive but positive outcomes could help to persuade quitting. METHOD: We use data from the longitudinal National Epidemiological Study of Alcohol and Related Conditions. Logistic regression was used to examine associations between cigarette smoking reduction and Wave 2 status of addiction/mental health disorder among daily smokers at Wave 1, stratified by status of the diagnosis of interest at Wave 1. We adjusted for differences in baseline covariates between smokers with different levels of smoking reduction between Wave 1 and Wave 2 using propensity score regression adjustment. RESULTS: After adjusting for propensity scores and other mental health/addiction comorbidities at Wave 2, among daily smokers who had current or lifetime history diagnosis of the outcome of interest at Wave 1, quitting by Wave 2 predicted a decreased risk of mood/anxiety disorder (aOR 0.6, 95% CI 0.4, 0.9) and alcohol disorder (aOR 0.7, 95% CI 0.5, 0.99) at Wave 2. Among daily smokers with no lifetime history diagnosis of the outcome of interest at Wave 1, quitting smoking by Wave 2 predicted a decreased risk of drug use disorder at Wave 2 aOR 0.3, 95% CI 0.1, 0.9). CONCLUSIONS: There is no support in our data for the concern that smoking cessation would result in smokers’ increased risk of some mental disorders. To the contrary, our data suggest that smoking cessation is associated with risk reduction for mood/anxiety or alcohol use disorder, even among smokers who have had a pre-existing disorder

Protocol for investigating genetic determinants of posttraumatic stress disorder in women from the Nurses' Health Study II

<p>Abstract</p> <p>Background</p> <p>One in nine American women will meet criteria for the diagnosis of posttraumatic stress disorder (PTSD) in their lifetime. Although twin studies suggest genetic influences account for substantial variance in PTSD risk, little progress has been made in identifying variants in specific genes that influence liability to this common, debilitating disorder.</p> <p>Methods and design</p> <p>We are using the unique resource of the Nurses Health Study II, a prospective epidemiologic cohort of 68,518 women, to conduct what promises to be the largest candidate gene association study of PTSD to date. The entire cohort will be screened for trauma exposure and PTSD; 3,000 women will be selected for PTSD diagnostic interviews based on the screening data. Our nested case-control study will genotype1000 women who developed PTSD following a history of trauma exposure; 1000 controls will be selected from women who experienced similar traumas but did not develop PTSD.</p> <p>The primary aim of this study is to detect genetic variants that predict the development of PTSD following trauma. We posit inherited vulnerability to PTSD is mediated by genetic variation in three specific neurobiological systems whose alterations are implicated in PTSD etiology: the hypothalamic-pituitary-adrenal axis, the locus coeruleus/noradrenergic system, and the limbic-frontal neuro-circuitry of fear. The secondary, exploratory aim of this study is to dissect genetic influences on PTSD in the broader genetic and environmental context for the candidate genes that show significant association with PTSD in detection analyses. This will involve: conducting conditional tests to identify the causal genetic variant among multiple correlated signals; testing whether the effect of PTSD genetic risk variants is moderated by age of first trauma, trauma type, and trauma severity; and exploring gene-gene interactions using a novel gene-based statistical approach.</p> <p>Discussion</p> <p>Identification of liability genes for PTSD would represent a major advance in understanding the pathophysiology of the disorder. Such understanding could advance the development of new pharmacological agents for PTSD treatment and prevention. Moreover, the addition of PTSD assessment data will make the NHSII cohort an unparalleled resource for future genetic studies of PTSD as well as provide the unique opportunity for the prospective examination of PTSD-disease associations.</p

Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression

Abstract Background Debate is ongoing about what role, if any, variation in the serotonin transporter linked polymorphic region (5-HTTLPR) plays in depression. Some studies report an interaction between 5-HTTLPR variation and stressful life events affecting the risk for depression, others report a main effect of 5-HTTLPR variation on depression, while others find no evidence for either a main or interaction effect. Meta-analyses of multiple studies have also reached differing conclusions. Methods/Design To improve understanding of the combined roles of 5-HTTLPR variation and stress in the development of depression, we are conducting a meta-analysis of multiple independent datasets. This coordinated approach utilizes new analyses performed with centrally-developed, standardized scripts. This publication documents the protocol for this collaborative, consortium-based meta-analysis of 5-HTTLPR variation, stress, and depression. Study eligibility criteria: Our goal is to invite all datasets, published or unpublished, with 5-HTTLPR genotype and assessments of stress and depression for at least 300 subjects. This inclusive approach is to minimize potential impact from publication bias. Data sources: This project currently includes investigators from 35 independent groups, providing data on at least N = 33,761 participants. The analytic plan was determined prior to starting data analysis. Analyses of individual study datasets will be performed by the investigators who collected the data using centrally-developed standardized analysis scripts to ensure a consistent analytical approach across sites. The consortium as a group will review and interpret the meta-analysis results. Discussion Variation in 5-HTTLPR is hypothesized to moderate the response to stress on depression. To test specific hypotheses about the role of 5-HTTLPR variation on depression, we will perform coordinated meta-analyses of de novo results obtained from all available data, using variables and analyses determined a priori. Primary analyses, based on the original 2003 report by Caspi and colleagues of a GxE interaction will be supplemented by secondary analyses to help interpret and clarify issues ranging from the mechanism of effect to heterogeneity among the contributing studies. Publication of this protocol serves to protect this project from biased reporting and to improve the ability of readers to interpret the results of this specific meta-analysis upon its completion.http://deepblue.lib.umich.edu/bitstream/2027.42/112319/1/12888_2013_Article_1474.pd