NEUROBIOLOGIC MECHANISMS OF DRUG ABUSE IN SCHIZOPHRENIA

精神分裂症药物滥用的神经生物学机制

• 批准号: 6391367
• 负责人: GERALDINE SCHELLER-GILKEY
• 金额: $ 12.15万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-15 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6391367
• 关键词: adrenocorticotropic hormone; age difference; blood chemistry; clinical research; comorbidity; corticosteroids; cortisol; dopamine; drug addiction; functional ability; gender difference; homovanillate; human subject; hypothalamic pituitary axis; interview; mental disorder diagnosis; neuroendocrine system; psychological stressor; schizophrenia; substance abuse related disorder

DESCRIPTION (Adapted from applicant's abstract): This proposal for a Mentored Research Scientist Development Award is designed to provide the candidate with training in the neurobiological sciences. The long-term goal is to establish the candidate as an independent investigator in the area of substance abuse and schizophrenia. The extremely high rate of co-morbidity of substance abuse and schizophrenia presents a serious problem in delivery of public mental health care to the chronically mentally ill. The candidate's preliminary studies on outpatients attending a community mental health clinic indicate that concurrent substance abuse is not only a common occurrence in schizophrenia patients (55 percent) but is also a major contributor to acute exacerbations as manifested by re-hospitalization. The candidate hypothesizes that these disorders share a common neurobiologic substrate involving the hypothalamic-pituitary-adrenal (HPA) axis and mesolimbic dopamine (DA) pathways. Specifically, it is the candidate's belief that in schizophrenia patients who become substance abusers, increases in stress hormones (corticosteroids) lead to increased mesolimbic DA activity, accompanied by an increase in psychotic symptoms, drug craving and sensitivity to drugs of abuse, enhancing the potential for addiction. To test this hypothesis, the following specific aims are proposed Aim 1: To characterize clinical features (including stress, depression and social support) of subjects with co-morbid substance abuse and schizophrenia as distinguished from subjects with schizophrenia or substance abuse alone, and healthy age-, sex- and race-matched controls. Aim 2: To characterize baseline neuroendocrine function (plasma ACTH, cortisol, and homovanillic acid (HVA)) in the four matched groups of subjects. Aim 3: To test the hypothesis that substance abusers will exhibit an increased dopaminergic response to cortisol administration with subsequently increased DA activity in mesolimbic pathways as assessed by plasma HVA, the Positive and Negative Symptom Scale, and Craving Indices. This research project, taken together with the training component of the proposal and the resources of Emory University, will help develop the candidate's skills as a researcher and will allow the candidate to make significant contributions to our understanding and treatment of co-morbid substance abuse and schizophrenia.

描述（改编自申请人的摘要）：本提案 指导研究科学家发展奖旨在提供 接受过神经生物科学培训的候选人。 远景目标 是确定候选人作为一个独立的调查员在该领域的 药物滥用和精神分裂症。 极高的合并症发病率 药物滥用和精神分裂症在分娩方面存在严重问题 公共精神健康护理的一部分。 的 候选人对社区精神科门诊病人的初步研究 健康诊所指出，同时滥用药物不仅是一种常见现象， 发生在精神分裂症患者（55%），但也是一个主要的 导致急性加重，表现为再次住院。 的 候选人假设这些疾病具有共同的神经生物学特性， 涉及下丘脑-垂体-肾上腺（HPA）轴的底物， 中脑边缘多巴胺（DA）通路。 具体来说，这是候选人的 相信在精神分裂症患者成为物质滥用者时， 应激激素（皮质类固醇）的增加导致中脑边缘系统的增加， DA活性增加，伴有精神病症状、药物渴求 和对滥用药物的敏感性，增加了成瘾的可能性。 为了检验这一假设，提出了以下具体目标 目的1：描述临床特征（包括应激、抑郁和 精神分裂症与药物滥用共病者社会支持 与单独患有精神分裂症或药物滥用的受试者不同， 以及年龄、性别和种族匹配的健康对照组。 目的2：表征基线神经内分泌功能（血浆ACTH， 皮质醇和高香草酸（HVA））在四个匹配组中， 科目 目的3：检验物质滥用者会表现出 对皮质醇给药的多巴胺能反应增加， 通过血浆HVA评估，中脑边缘通路中DA活性增加， 阳性和阴性症状量表和渴望指数。 这项研究项目，连同培训部分， 建议和埃默里大学的资源，将有助于发展 候选人的技能作为一个研究人员，并将允许候选人，使 对我们理解和治疗共病的重大贡献 药物滥用和精神分裂症。