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Sex differences in BNST networks during early abstinence in AUD

AUD 早期戒断期间 BNST 网络的性别差异

基本信息

批准号：
10686106
负责人：
JENNIFER URBANO BLACKFORD
金额：
$ 59.48万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-20 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10686106
关键词：
Abstinence Acute Address Alcohol consumption Alcohol dependence Alcohol withdrawal syndrome Alcohols American Animal Model Animals Anxiety Awareness Behavior Brain Brain region Chronic Data Dependence Development Diffusion Magnetic Resonance Imaging Disease Female Functional Magnetic Resonance Imaging Functional disorder Funding Funding Agency Future Galvanic Skin Response Health Homeostasis Human Hydrocortisone Hyperactivity Influentials Intervention Intoxication Knowledge Light Measures Mediating Mental Depression Methods National Institute on Alcohol Abuse and Alcoholism Negative Reinforcements Neurobiology Occupations Pattern Physiology Pilot Projects Process Publishing Relapse Research Rest Role Sex Differences Stress Structure of terminal stria nuclei of preoptic region Symptoms System Testing Translational Research Withdrawal Woman addiction alcohol abstinence alcohol abuse therapy alcohol consequences alcohol exposure alcohol seeking behavior alcohol use disorder anxiety symptoms biological adaptation to stress clinically significant depressive symptoms drinking effective therapy experience in vivo long term recovery male men negative affect neural network novel personalized medicine relapse prevention response sex sexual dimorphism stress related disorder theories

项目摘要

Alcohol use disorders (AUDs) are common, disabling conditions. There is a growing awareness of important sex differences in AUDs; for example, women experience more serious health complications from alcohol use and also develop negative consequences from alcohol use more quickly. While the rate of AUDs is relatively stable in men, the rate in women is escalating at an alarming rate. Neurobiological differences between sexes are thought to underlie the differential impact of AUDs in men and women, but to date relatively few studies on this topic exist. Animal models of addiction have substantially informed our understanding of the stages of addiction— binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation—and their underlying pathophysiology. For example, chronic alcohol exposure causes neuroadaptive brain changes in an attempt to maintain homeostasis. During the withdrawal/negative affect stage, hyperactive stress systems produce symptoms including anxiety and depression which are thought to lead to relapse through negative reinforcement. Women have higher rates of anxiety and stress-related disorders, which may contribute to sex differences in early abstinence. Animal models of early abstinence from alcohol highlight the involvement the bed nucleus of the stria terminalis (BNST). The BNST is also one of the most sexually dimorphic brain regions, suggesting the BNST is involved in sex-related differences seen during early abstinence. We previously published evidence for sex differences in BNST structural connectivity in humans. In addition, pilot data from our NIAAA funded R21 provide initial evidence for sex differences: females had stronger structural and functional connectivity within the BNST network, heightened stress responses, and higher anxiety during early abstinence. The current study will focus on sex differences in the BNST network during early abstinence from alcohol by investigating three specific aims: (1) Determine whether there are sex-related differences in BNST intrinsic functional or structural connectivity during early abstinence; (2) Determine whether there are sex- related differences in stress-related BNST function and BNST network connectivity during early abstinence; (3) Investigate sex-related differences in the relationship between BNST function/connectivity, stress response, and negative affect in early abstinence. Based on findings from animal models and our pilot data in humans, we predict that during early abstinence, the BNST will show sex-specific differences in patterns of activity and connectivity “at-rest” and in response to a mildly stressful task. We expect women will show stronger structural and functional connectivity within the BNST network, heightened stress responses, and higher anxiety during early abstinence. The successful completion of this study will fill a critical knowledge gap, determining whether men and women show neurobiological differences in BNST networks underlying negative affect during early abstinence from alcohol. The results will provide foundational information to inform future studies investigating mechanisms of relapse and can guide the development of sex-specific or personalized treatments for AUD.

酒精使用障碍（AUDs）是一种常见的致残状况。人们越来越意识到……的重要性