Inhibitory Deficits in Bipolar Disorder and Methamphetamine Dependence

双相情感障碍和甲基苯丙胺依赖的抑制缺陷

• 批准号: 7766991
• 负责人: Brook Henry
• 金额: $ 5.22万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7766991
• 关键词: Ambulatory Monitoring; Amphetamines; Attenuated; Basal Ganglia; Behavior; Behavioral; Bipolar Disorder; Brain region; Cardiac; Chronic; Clinical; Clinical Trials; Clinical assessments; Cognition; Cognitive; Data; Development; Diagnosis; Disease; Dopamine; Drug Addiction; Drug abuse; Elements; Environment; Etiology; Exhibits; Failure; Functional disorder; Funding; Furniture; Genetic; Goals; Gold; Human; Hyperactive behavior; Impulsivity; Individual; Inpatients; Knock-out; Manic; Measures; Mediating; Mental disorders; Methamphetamine; Methamphetamine dependence; Modeling; Monitor; Mood Disorders; Moods; Motor; Motor Activity; Neurobiology; Outpatients; Participant; Pathology; Pattern; Pharmacological Treatment; Population; Prefrontal Cortex; Psychiatry; Recording of previous events; Regulation; Reporting; Request for Applications; Respiration; Rodent; Rodent Model; Severities; Substance Addiction; Substance abuse problem; Symptoms; System; Tactile; Testing; Translational Research; Treatment outcome; United States; Wages; Work; base; cost; design; disability; dopamine transporter; improved; innovation; monitoring device; neuropsychiatry; neurotoxic; novel; public health relevance; relating to nervous system; research study; response; ward

DESCRIPTION (provided by applicant): Inhibition, i.e. the ability to withhold or attenuate an action or a thought, is of central importance in the regulation of behavior. Inhibitory deficits are key features of Bipolar Disorder (BD) and substance abuse disorders, including methamphetamine (MA) dependence. BD is one of the leading causes of disability worldwide, with an estimated cost of 96 million lost workdays and 14 billion dollars in salary per year in the United States alone. Although comorbid drug abuse has been reported to occur in a majority of BD individuals and is associated with more severe psychiatric symptoms and worse treatment outcome, most research studies and clinical trials involving BD have excluded subjects with a history of drug abuse. The objective of the current project is to examine the effect of both MA dependence and BD on deficits in inhibition using a novel human open field paradigm that we have developed in our lab. The assessment of inhibitory failure in BD individuals with concurrent MA dependence will enable the development of a model that may be used to predict novel treatments for these pathologies and help to identify the neural substrates underlying these disorders. Inhibitory deficits manifest as increased hyperactivity, perseverative behavior, and symptoms characterized by impulsivity, including increased responses to novelty. The first aim of this project will assess the effect of MA and BD on these behaviors in individuals placed into a novel room where locomotor activity, perseverative motor responses, and interactions with novel objects are quantified. Based on evidence for activation/sensitization of the dopaminergic system in the basal ganglia and damage to the prefrontal cortex, a region of the brain that mediates inhibition of behavior, we predict the most severe inhibitory deficits will be observed in BD individuals with a chronic history of MA dependence. The second aim of our project will examine the relationship between the clinical assessment of mania and deficits in inhibition in our human open field paradigm. We predict that increased manic symptoms, as measured by the Young Mania Rating Scale, will show a significant correlation with increased inhibitory deficits. PUBLIC HEALTH RELEVANCE: Our understanding and treatment of BD and the effects of concurrent drug dependence will greatly benefit from the development of a human model of the behavior dysfunction that occurs in this population. This project will improve our understanding of the etiology and pathology of BD and uses a paradigm that can help to diagnose and test treatments for the mood and substance abuse disorders.

描述（由申请人提供）：抑制，即抑制或减弱某种行为或想法的能力，在行为调节中至关重要。抑制缺陷是双相情感障碍 (BD) 和药物滥用障碍（包括甲基苯丙胺 (MA) 依赖）的关键特征。 BD 是全球残疾的主要原因之一，据估计，仅在美国每年就造成 9600 万个工作日的损失和 140 亿美元的工资损失。尽管据报道大多数双相障碍患者都存在药物滥用共病，并且与更严重的精神症状和更差的治疗结果相关，但大多数涉及双相障碍的研究和临床试验都排除了有药物滥用史的受试者。 当前项目的目标是使用我们在实验室开发的新型人类开放领域范例来检查 MA 依赖性和 BD 对抑制缺陷的影响。对同时患有 MA 依赖的 BD 个体的抑制失败的评估将有助于开发一个模型，该模型可用于预测这些病理的新疗法，并有助于识别这些疾病背后的神经基质。 抑制缺陷表现为多动、持续行为和以冲动为特征的症状增加，包括对新奇事物的反应增加。该项目的第一个目标是评估 MA 和 BD 对放置在新房间中的个体的这些行为的影响，在该房间中，对运动活动、持续运动反应以及与新物体的相互作用进行量化。基于基底神经节多巴胺能系统的激活/敏化以及前额皮质（大脑中介导行为抑制的区域）受损的证据，我们预测在具有长期 MA 依赖史的 BD 个体中将观察到最严重的抑制缺陷。我们项目的第二个目标将检查躁狂症的临床评估与人类开放领域范式中的抑制缺陷之间的关系。我们预测，通过年轻躁狂评定量表测量的躁狂症状的增加将与抑制缺陷的增加显示出显着的相关性。 公共卫生相关性：我们对双相情感障碍以及并发药物依赖的影响的理解和治疗将极大地受益于该人群中发生的行为功能障碍的人类模型的开发。该项目将提高我们对双相情感障碍病因学和病理学的理解，并使用有助于诊断和测试情绪和药物滥用障碍治疗方法的范例。