SUBSTANCE ABUSE VULNERABILITY AND PREFRONTAL METABOLISM

精神活性物质滥用障碍(PSUD)的责任是 是多因素的，包括生物、心理和社会领域。 然而，人们对神经生物学特征知之甚少 可能会增加PSUD的风险。PSUD漏洞增加 与行为障碍有关，如行为障碍(CD 儿童和青春期，以及成人中的反社会人格障碍。 有来自神经心理学、神经成像和 神经生理学研究表明这些行为障碍是相关的 伴随着大脑前额叶皮质的功能障碍。因此，我们 假设责任的行为和神经生物学成分 TO PSUD与前额叶皮质能量的变化有关 体内31P可检测到的膜磷脂代谢 磁共振光谱学。 这项探索性研究(R21)的具体目标是： 1)研究早发性品行障碍、家族性 前额叶皮质能量和脑功能不同者患PSUD的风险 活体31P磁共振测定磷脂代谢 光谱学。 2)确定前额叶皮质大脑能量之间的关系 代谢和膜磷脂代谢活性与性状和 国家对攻击性、注意力不集中、冲动和多动的衡量标准； 这些行为被认为是PSUD的重要组成部分 脆弱性，也被观察到是一种 前额叶脑功能障碍。 根据探索性赠款方案的指导方针， 建议的调查是在生物医学研究的一条未开发的道路上， 利用新技术在现有的 旨在描述药物滥用参数的前瞻性家庭研究 病因学。这一项目旨在论证其可行性 以及31P磁共振波谱的潜在价值，作为一种特异性 表征神经生物学基础的生物医学方法 PSUD漏洞。

The liability for a psychoactive substance abuse disorder (PSUD) is multifactorial and comprises biological, psychological and social domains. However, very little is known about neurobiological characteristics that may contribute to the risk for PSUD. Increased vulnerability for PSUD has been linked to behavioral disorders, such as Conduct Disorder (CD) in childhood and adolescence, and Antisocial Personality Disorder in adults. There is converging evidence from neuropsychological, neuroimaging, and neurophysiological studies that these behavior disorders are associated with a disfunction of the prefrontal cortex of the brain. Consequently, we postulate that a behavioral and neurobiological component of the liability to PSUD is associated with a variation in prefrontal cortex energy and membrane phospholipid metabolism that is detectable by in vivo 31P magnetic resonance spectroscopy. The specific aims of this exploratory (R21) study are: 1) Examine the association between early-onset Conduct Disorder, familial risk for PSUD with variations in prefrontal cortical cerebral energy and phospholipid metabolism measured by in vivo 31P magnetic resonance spectroscopy. 2) Determine the associations between prefrontal cortical cerebral energy metabolism and membrane phospholipid metabolic activity with trait and state measures of aggression, inattention, impulsivity and hyperactivity; these behaviors are implicated to be important components of PSUD vulnerability and have also been observed to be manifestations of a prefrontal brain dysfunction. In keeping with the guidelines of the exploratory grants program, the investigation proposed is in an undeveloped avenue of biomedical research, utilizing a novel technology to be carried out within an existing prospective family study aimed at delineating the parameters of drug abuse etiology. This project is directed toward demonstrating the feasibility and potential value of 31P magnetic resonance spectroscopy, as a specific biomedical method for the characterization of a neurobiological basis of PSUD vulnerability.