Addiction and Subsequent Schizophrenia: A Link?

描述（由申请人提供）： 这个指导以患者为导向的研究职业发展（K23）奖的目的是研究药物滥用与青少年和年轻人精神分裂症的后续发展之间的联系。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，大脑奖励回路的功能障碍可能只会在有即时奖励期望时导致决策障碍。在精神分裂症中，前额叶皮层缺陷可能导致决策障碍，而不依赖于即时奖励期望。 该奖项有三个具体目的来调查这一假设：（1）评估和比较大麻滥用者与精神分裂症患者、精神分裂症患者和正常对照者之间在有和没有立即奖励期望的情况下的决策任务;（2）检查决策过程、阴性症状、精神分裂症患者治疗初期和治疗一年后前额叶皮层神经认知功能的变化;（3）检查决策与性别、行为和反社会人格障碍、冲动控制障碍、和症状维度。 该奖项的主要职业发展活动包括：（1）前额叶皮层决策和认知评估的教学计划;（2）参与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首次精神病发作患者，跟踪他们的治疗反应和神经认知;（3）设计、实施和分析一项研究，该研究使用计算机化决策任务，有或没有立即奖励。 该奖项的长期目标是：（1）获得成瘾的精神病学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的决策领域。修订后的申请通过以下方式得到了加强：（1）将研究项目集中在大麻滥用上，这将导致对更同质的患者群体进行研究，并增加统计功效;（2）增加神经科学和神经成像方面的培训;（3）通过与首次精神病发作研究有关的额外信息澄清研究设计。

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.