Neuropsychobiology in Polysubstance Abusers during Abstinence

多物质滥用者禁欲期间的神经心理生物学

基本信息

批准号：
9414009
负责人：
DIETER J MEYERHOFF
金额：
$ 53.97万
依托单位：
NORTHERN CALIFORNIA INSTITUTE/RES/EDU
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9414009
关键词：
Abstinence Affect Aftercare Alcohol abuse Alcohol consumption Alcohol dependence Alcohol or Other Drugs use Alcohols Anterior Antioxidants Behavior Behavior Control Behavior Therapy Biological Biology Blood flow Brain Brain Injuries Brain imaging Brain region Cerebrum Chronic Clinical Research Cognition Cognitive Cognitive deficits Communities Comorbidity Corpus striatum structure Data Decision Making Development Disease Disease remission Drug abuse Drug usage Energy Metabolism Frequencies Functional disorder Future General Population Gliosis Glutamates Glutathione Goals Health behavior Hypertrophy Illicit Drugs Impulsive Behavior Individual Inferior Inflammatory Informal Social Control Injury Knowledge Learning Magnetic Resonance Measurement Measures Memory Metabolic Methamphetamine Monitor Morphology National Institute of Drug Abuse Nature Neurobiology Neurocognition Neurocognitive Deficit Neuronal Injury Neuronal Plasticity Neurons Neuropsychology Neurotransmitters Oxidative Stress Pattern Perception Perfusion Peripheral Pharmaceutical Preparations Pharmacological Treatment Pharmacology Pharmacotherapy Policies Population Prevalence Public Opinion Quality of life Recording of previous events Recovery Relapse Research Research Personnel Resources Risk Risk-Taking Sampling Severities Short-Term Memory Smoking Substance abuse problem System Testing Thinness Time Tobacco Tobacco use Training Translational Research United States addiction alcohol abstinence alcohol comorbidity alcohol use disorder base brain abnormalities cigarette smoking clinical predictors clinically relevant cocaine use cognitive control cognitive performance cohort cytokine drug abstinence drug use vulnerability effective therapy functional improvement improved magnetic field marijuana use disorder multimodality neuroadaptation neuroimaging novel polysubstance abuse pre-clinical research processing speed public health relevance relapse prediction relapse risk response skills social stigma sociodemographics substance abuse treatment substance misuse targeted treatment treatment group white matter

项目摘要

DESCRIPTION (provided by applicant): Polysubstance use disorder (PSUD) is more common among treatment seekers today than monosubstance use disorders. Chronic cigarette smoking is more prevalent among treated substance users than in the general population, and it is more prevalent in polysubstance users (PSU) than monosubstance users. Yet, very little is known about the neurobiological effects of PSUD and comorbid smoking, their potential relationships to neuro- cognition and related substance use behavior, or about effective treatment of PSUD. Extensive brain imaging and cognitive research indicate that monosubstance use is associated with abnormal brain biology and function that facilitate continued misuse; some of these brain abnormalities partially recover with abstinence. Further, smoking has clear detrimental effects on brain biology and function in monosubstance users (alcohol, methamphetamines), even in otherwise healthy controls. Notably, our preliminary studies show that brain abnormalities in PSU are different in extent, nature, and impact on cognition and behavior than in `pure' alcohol dependent samples with similar alcohol and tobacco use histories, and that both neurobiology and cognition improve in PSU over 3 months of abstinence. The ethnic and sociodemographic composition of PSU treatment cohorts is also distinctly different from that of `pure' alcohol dependent cohorts, altogether suggesting that they constitute different populations. We propose to study a well-defined and well-characterized group of PSU at 1- 3 weeks of abstinence with select brain magnetic resonance (MR), cognition, and self-regulation measures, to re-study abstinent PSU 3 months later, and to relate cross-sectional and longitudinal change measures to relapse and substance use assessed 6-9 months after baseline. Our regional focus is on fronto-striatal brain critical for achieving and maintaining long-term abstinence in addictive disorders. Our neuro-psychological focus is on traditional cognitive domains and measures of impulsive behavior and cognitive control. Our main neurobiological focus is on oxidative stress (OxS), hypothesized to underlie both PSUD and chronic smoking, and the neurobiological and systemic correlates of OxS. We further hypothesize that specific cognitive and regional MR abnormalities improve with abstinence and that longitudinal change measures during early remission predict subsequent relapse better than the corresponding cross-sectional measures. Additional MR measures will probe fronto-striatal neuronal injury, gliosis, glutamatergic and GABA-ergic effects, and perfusion deficits as they relate to cognition, self-regulation, and substance and tobacco use pre- and post-treatment. Studies will be conducted in treatment seekers with comorbid alcohol and cocaine use disorders (moderate to severe), with or without tobacco and mild cannabis use disorder. This hypotheses-driven proposal is aimed at identifying multifaceted determinants of continued substance misuse or abstinence as potential new targets for pharmacological and behavioral treatment of PSU. Showing neurobiological and functional improvements with abstinence will also help move public opinion to a mindset more helpfully described as `your brain in recovery'.

描述（由适用提供）：当今寻求治疗的人在治疗者中比单体立场使用障碍更为常见。在治疗的药物使用者中，长期吸烟比一般人群更为普遍，并且在多物质使用者（PSU）中，它比单肥大用户更为普遍。然而，对于PSUD和合并吸烟的神经生物学作用，它们与神经认知和相关药物使用行为的潜在关系或有效治疗PSUD的潜在关系，知之甚少。广泛的大脑成像和认知研究表明，单材的使用与持续失误的异常脑生物学和功能有关。这些大脑异常中的一些部分以戒酒为部分恢复。此外，即使在其他健康对照中，吸烟对脑生物学和功能也有明显的有害影响。值得注意的是，我们的初步研究表明，PSU的大脑异常在程度，性质和对认知和行为的影响不同于与酒精和烟草使用史相似的“纯”酒精依赖性样品，并且神经生物学和认知在3个月以来，PSU的神经生物学和认知都可以改善。 PSU治疗队列的种族和社会人口统计学组成也与“纯”酒精依赖的同类群体明显不同，完全表明它们构成了不同的人群。我们建议在节制1-3周以选择精选的脑磁共振（MR），认知和自我调节度量的1-3周进行研究，以便在3个月后重新研究PSU，并在3个月后拒绝PSU，并在底部和纵向变化措施中进行底部和纵向变化，以评估6-9个月后使用6-9个月。我们的区域重点是额叶纹状体大脑对于实现和维持累加障碍的长期戒酒至关重要。我们的神经心理重点是传统的认知领域和脉冲行为和认知控制的度量。我们的主要神经生物学重点是氧化应激（OX），假设是PSUD和慢性吸烟的基础，以及OX的神经生物学和全身相关性。我们进一步假设，特定的认知和区域MR异常随着禁欲而改善，并且在早期缓解期间的纵向变化测量值比相应的横截面测量更好地预测随后的缓解。额外的MR测量将探测额纹状体神经元损伤，神经胶质病，谷氨酸能和GABA - 富含作用，并且灌注与认知，自我调节以及物质以及烟草一起使用前后使用前和烟草的灌注定义。研究将在患有合并酒精和可卡因使用障碍（中度至重度）的寻求治疗者中进行研究，有或没有烟草和轻度大麻使用障碍。该假设驱动的建议旨在确定持续滥用或戒酒确定的多方面是PSU的药物和行为处理的潜在新目标。表现出具有禁欲的神经生物学和功能改进也将有助于将公众舆论更加有帮助地描述为“康复中的大脑”。