Addiction and Subsequent Schizophrenia: A Link?

描述(由申请人提供)： 这项以病人为本的研究生涯发展奖(K23)旨在研究药物滥用与青少年精神分裂症发展之间的关系。理解这种联系的一个关键因素可能是决策过程：在药物滥用中，只有在存在直接的奖励预期时，大脑奖励回路的功能障碍才可能导致决策障碍。在精神分裂症患者中，前额叶皮质缺陷可能会导致决策障碍，而不受直接奖励期望的影响。 该奖项有三个具体目的来考察这一假设：(1)评估和比较有或没有精神分裂症的大麻滥用者、有精神分裂症但没有药物滥用的患者和正常对照组之间的决策任务；(2)考察精神分裂症患者在最初和治疗一年后决策过程、阴性症状和神经认知功能之间的关系；(3)研究决策与性别、行为和反社会人格障碍、冲动控制障碍和症状维度等变量之间的关联。 该奖项的主要职业发展活动包括(1)对前额叶皮质的决策和认知评估的教学计划；(2)参加一项正在进行的大型临床试验，比较有和没有药物滥用史的第一次精神病发作的患者，跟踪他们的治疗反应和神经认知；(3)设计、实施和分析一项使用计算机决策任务的研究，包括有和没有立即奖励的情况。 该奖项的长期目标是：(1)获得成瘾的精神后果方面的专业知识；(2)在希尔赛德医院开发旨在改善双重诊断患者护理的研究项目；(3)在希尔赛德医院介绍研究和临床项目中的决策领域。这一修订后的应用通过以下方式得到加强：(1)将研究项目的重点放在大麻滥用上，这将导致对更同质的患者群体的研究，并增加统计能力；(2)增加神经科学和神经成像方面的培训；以及(3)澄清研究设计，提供与第一次精神病发作研究有关的额外信息。

DESCRIPTION (provided by applicant): The purpose of this Mentored Patient-Oriented Research Career Development (K23) Award is to study the linkage between substance abuse and the subsequent development of schizophrenia in adolescents and young adults. A key element in understanding this linkage may be the decision-making process: In substance abuse, a dysfunction of the brain reward circuit may result in an impairment in decision-making only when there is an immediate reward expectancy. In schizophrenia, a prefrontal cortical deficit may result in an impairment in decision-making independent of immediate reward expectancy. This award has three specific aims for investigating this assumption: (1) to assess and compare decision-making tasks with and without immediate reward expectancy between cannabis abusers with and without schizophrenia, patients with schizophrenia and no substance abuse, and normal controls; (2) to examine the association between the decision-making process, negative symptoms, and neurocognitive functions of the prefrontal cortex in schizophrenia patients initially and after one year of treatment; (3) to examine the association between decision-making and variables such as gender, conduct and antisocial personality disorders, impulse control disorders, and symptom dimensions. Major career development activities of this award are (1) didactic programs in decision-making and cognitive assessments of the prefrontal cortex; (2) participation in a large ongoing clinical trial comparing patients experiencing their first episode of psychosis, with and without a history of substance abuse, following them for treatment response and neurocognition; (3) the design, conduct and analyses of a study using computerized decision-making tasks with and without immediate reward. Long-term objectives of this award are: (1) to gain expertise in the psychiatric consequences of addiction; (2) to develop research programs at Hillside Hospital aimed at improving the care of dual-diagnosis patients; (3) to introduce the field of decision-making in research and clinical programs at Hillside Hospital. This revised application has been strengthened by (1) focusing the research project on cannabis abuse, which will result in the study of more homogenous groups of patients and increased statistical power; (2) adding training in neuroscience and neuroimaging; and (3) clarifying the study design with additional information pertaining to the first-psychotic episode study.