Brain Mechanisms of Adolescent Bipolar Disorder as Risk Factor for Drug Abuse

青少年双相情感障碍作为药物滥用危险因素的脑机制

• 批准号: 8771972
• 负责人: Alessandra Maria Passarotti
• 金额: $ 23.89万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8771972
• 关键词: 16 year old; Abstinence; Adolescence; Adolescent; Adopted; Affective; Age; Aggressive behavior; Amygdaloid structure; Anterior; Behavior; Behavioral; Biological; Bipolar Disorder; Brain; Cannabis; Clinical; Cognitive; Cognitive deficits; Collection; Comorbidity; Cues; Data; Decision Making; Dorsal; Drug Addiction; Drug abuse; Early Diagnosis; Event; Exhibits; Failure; Figs - dietary; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Hypersensitivity; Illness impact; Impulsivity; Incentives; Individual; Informal Social Control; Knowledge; Lateral; Lead; Maps; Marijuana; Measures; Medial; Mental disorders; Methods; Modeling; Nature; Neurobiology; Neurocognitive; Neurophysiology - biologic function; Outcome; Participant; Patients; Pattern; Phase; Phenotype; Pilot Projects; Populations at Risk; Process; Relapse; Relative (related person); Rewards; Risk; Risk Factors; Self-control as a personality trait; Severity of illness; Subgroup; Substance abuse problem; Suicide; Suicide attempt; System; Testing; Time; Ventral Striatum; Work; addiction; adolescent substance abuse; animal data; base; cingulate cortex; compliance behavior; craving; design; discounting; drug reward; early onset; expectation; human data; insight; neural circuit; neurobiological mechanism; neuropsychological; preference; psychologic; public health relevance; relating to nervous system; response

DESCRIPTION (provided by applicant): Adolescence is a vulnerable time for developing drug addiction, and adolescents who suffer from adolescent bipolar disorder (ABD) are particularly at risk due to the explosive interaction between severe affective dysregulation, impaired self-control, and excessive reward-seeking behavior. In particular, marijuana (cannabis) is the most common illicit substance abused by teenage BD patients. Significant cannabis use in ABD can substantially worsen clinical outcome, with dramatic increases in illness severity, cognitive and affective worsening, and suicide attempts. The nature of the high comorbidity between cannabis use and ABD in the adolescent years, when the brain is still developing, has scarcely been investigated. For the first time, with this pilot study we aim to characterize the mechanistic neuro-circuitry dysfunction associated with high comorbidity between adolescent mental illness such as ABD and SCU (significant cannabis use). Using clinical, neurocognitive, and advanced fMRI methods we will test a model of two brain circuits highly implicated in both drug abuse and bipolar disorder: the reward system and the self-control system. We will test 22 adolescents with significant cannabis use (SCU group), 22 adolescents with ABD and SCU (ABD+SCU group), and 22 healthy controls (HC) using tasks measuring reward sensitivity, and self-control during decision-making involving rewards. All participants with be 14-16 year olds and will be matched on IQ and demographic measures. Our overarching hypothesis is that the fronto-limbic abnormalities typical of bipolar disorder will exacerbate dysfunction in the reward and self-control systems in the ABD+SCU group. This group will exhibit greater reward sensitivity and poorer self-control, associated with hyperactive ventral striatum and amygdala and diminished prefrontal control, relative to the SCU group. Findings from this much needed study will provide a first step towards important neurobiological cues on excessive craving, reward sensitivity and deficient self- control in these patients so difficult to treat. By studying a more homogeneous subgroup with SCU+ABD we may provide insights into drug abuse that were previously unclear due to more heterogeneous collections of SCU. Hence, our findings may extend also to other psychiatric disorders, and give new insights into methods for early detection of SCU.

描述（由申请人提供）：青春期是吸毒成瘾的脆弱时期，患有青少年双相情感障碍（ABD）的青少年尤其面临风险，因为严重的情感失调、自我控制受损和过度奖励之间的爆炸性相互作用- 寻求行为。特别是，大麻是青少年双相情感障碍患者最常见滥用的非法物质。在 ABD 中大量使用大麻会严重恶化临床结果，导致疾病严重程度、认知和情感恶化以及自杀企图急剧增加。在青少年时期，当大脑仍在发育时，吸食大麻与 ABD 之间高度共存的性质几乎没有被研究过。通过这项试点研究，我们首次旨在描述与 ABD 和 SCU（大量使用大麻）等青少年精神疾病之间的高合并症相关的机械性神经回路功能障碍。使用临床、神经认知和先进的功能磁共振成像方法，我们将测试与药物滥用和双相情感障碍高度相关的两个大脑回路模型：奖励系统和自我控制系统。我们将使用测量奖励敏感性以及涉及奖励的决策过程中的自我控制的任务来测试 22 名大量使用大麻的青少年（SCU 组）、22 名患有 ABD 和 SCU 的青少年（ABD+SCU 组）以及 22 名健康对照者（HC） 。所有参与者均为 14-16 岁，并将在智商和人口统计指标上进行匹配。我们的总体假设是，双相情感障碍典型的额叶边缘异常会加剧 ABD+SCU 组奖励和自我控制系统的功能障碍。相对于 SCU 组，该组将表现出更高的奖励敏感性和较差的自我控制能力，这与腹侧纹状体和杏仁核过度活跃以及前额叶控制减弱有关。这项急需的研究结果将为寻找重要的神经生物学线索提供第一步，这些线索涉及这些难以治疗的患者的过度渴望、奖励敏感性和自我控制缺陷。通过使用 SCU+ABD 研究更同质的亚组，我们可以提供有关药物滥用的见解，而这些见解以前由于 SCU 的异质性集合而不清楚。因此，我们的研究结果也可能扩展到其他精神疾病，并为早期检测 SCU 的方法提供新的见解。