Neuropsychobiology in Polysubstance Abusers during Abstinence

多物质滥用者禁欲期间的神经心理生物学

• 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
• 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

 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（由申请人提供）：如今，多物质使用障碍 (PSUD) 在寻求治疗的人中比单一物质使用障碍更常见。长期吸烟在治疗药物使用者中比在一般人群中更为普遍，并且在多物质使用者 (PSU) 中比单一物质使用者中更普遍。然而，人们对 PSUD 和共病吸烟的神经生物学影响、它们与神经认知和相关物质使用行为的潜在关系或 PSUD 的有效治疗知之甚少。广泛的脑成像和认知研究表明，单一物质的使用与大脑生物学和功能异常有关，从而导致持续滥用；其中一些大脑异常可通过禁欲而部分恢复。此外，吸烟对单一物质（酒精、甲基苯丙胺）使用者的大脑生物学和功能有明显的有害影响，即使是在其他方面健康的对照组中也是如此。值得注意的是，我们的初步研究表明，与具有类似饮酒和吸烟史的“纯”酒精依赖样本相比，PSU 中的大脑异常在程度、性质以及对认知和行为的影响方面有所不同，并且在戒酒 3 个月后，PSU 的神经生物学和认知能力均得到改善。 PSU 治疗队列的种族和社会人口组成也与“纯”酒精依赖队列明显不同，这表明它们构成了不同的人群。我们建议在戒断 1-3 周时研究一组明确且特征明确的 PSU，并选择脑磁共振 (MR)、认知和自我调节措施，并在 3 个月后重新研究戒断 PSU，并将横断面和纵向变化测量与基线后 6-9 个月评估的复发和物质使用联系起来。我们的区域重点是额纹状体大脑，这对于实现和维持成瘾性疾病的长期戒断至关重要。我们的神经心理学重点是传统的认知领域以及冲动行为和认知控制的测量。我们的主要神经生物学重点是氧化应激 (OxS)，假设它是 PSUD 和慢性吸烟的基础，以及 OxS 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 异常随着戒酒而改善，并且早期缓解期间的纵向变化测量比相应的横截面测量更好地预测随后的复发。其他 MR 测量将探测额纹状体神经元损伤、神经胶质增生、谷氨酸能和 GABA 能效应以及灌注缺陷，因为它们与治疗前后的认知、自我调节、物质和烟草使用有关。研究将对患有酒精和可卡因使用障碍（中度至重度）、患有或不患有烟草和轻度大麻使用障碍的寻求治疗者进行。这一假设驱动的提案旨在确定持续物质滥用或戒断的多方面决定因素，作为 PSU 药物和行为治疗的潜在新目标。通过禁欲表现出神经生物学和功能的改善也将有助于将公众舆论转移到一种更有帮助的心态，即“你的大脑正在康复”。