NEUROBIOLOGIC MECHANISMS OF DRUG ABUSE IN SCHIZOPHRENIA

描述(改编自申请人的摘要)：本建议书 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。长期目标 是将候选人确立为该领域的独立调查员 药物滥用和精神分裂症。极高的并存率 药物滥用和精神分裂症是分娩中的一个严重问题 向慢性精神病患者提供公共精神卫生保健服务。这个 应聘者参加社区精神科门诊的初步研究 健康诊所表明，并发药物滥用不仅是一种常见的 在精神分裂症患者中发生(55%)，但也是一个主要的 再次住院表现为急性加重的诱因。这个 候选人假设这些疾病具有共同的神经生物学特征 底物涉及下丘脑-垂体-肾上腺(HPA)轴和 中脑边缘多巴胺(DA)通路。具体地说，这是候选人的 相信在成为物质滥用者的精神分裂症患者中， 应激激素(皮质类固醇)的增加导致中脑边缘的增加 DA活动时，伴有精神症状增多、药物渴求 以及对滥用药物的敏感性，增加了上瘾的可能性。 为了验证这一假设，提出了以下具体目标 目标1：描述临床特征(包括应激、抑郁和 社会支持)与药物滥用和精神分裂症共病 与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。 目的2：测定基线神经内分泌功能(血浆促肾上腺皮质激素， 皮质醇和高香草酸(HVA)在四个匹配的组中 研究对象。 目标3：检验物质滥用者将表现出 皮质醇给药后多巴胺能反应增强 用血浆HVA评价中脑边缘通路DA活性的增加 阳性症状量表、阴性症状量表、渴求指数。 这项研究项目与 提案和埃默里大学的资源，将有助于开发 应聘者作为研究人员的技能，并将使应聘者 对我们理解和治疗并存疾病有重大贡献 药物滥用和精神分裂症。

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.