Schizophrenia risk to onset: Neurobiology and prevention

描述(由申请人提供)：本次修订后的以患者为导向的研究职业发展奖(K23)申请书为谢丽尔·科克伦博士提出了一项计划，以便在精神分裂症前驱症状的前瞻性评估中进行培训和研究，特别是与精神病发病相关的风险因素、干预变量和标记。培训和研究计划的目标是围绕这样一个假设进行整合的，即精神分裂症易感性的神经素质涉及在心理社会压力的背景下发展成精神病的脆弱性。科克伦博士目前在研究1)精神分裂症的前驱症状和2)精神分裂症的压力暴露及其相关性方面拥有丰富的经验。在Malaspina博士的赞助下，并利用NYSPI/Columbia和Hillside医院的资源，Corcoran博士的培训计划将正式课程和直接监督与临床研究经验和培训结合在一起。科克伦博士在NYSPI建立了一个前驱症状研究诊所，名为“预防和评估中心”(COP)。培训计划包括1)评估精神分裂症的压力和HPA轴的临床方法(Malaspina)；2)增加前驱研究和神经心理学方面的专门知识(Cornblatt)；3)纵向研究中的数据分析(Begg)；4)青少年认知和社会发展(Kestenbuam)。这项研究计划是对前驱症状患者进行的前瞻性队列研究，采用临床方法探讨HPA轴功能、前驱症状和心理社会应激暴露。假设基线应激反应(应激反应性皮质醇和对正常应激的耐受性受损)和干预生活事件将增加前驱症状患者的精神病风险。重要的协变量也被评估，包括认知、早期创伤、药物和物质使用。这项研究将为申请者提供必要的知识和研究经验，以申请R01，以进一步评估先兆患者精神病发病的危险因素、介体和标记物。

DESCRIPTION (provided by applicant): This revised application for a Mentored Patient-Oriented Research Career Development Award (K23) presents a plan for Dr. Cheryl Corcoran to pursue training and research in the prospective assessment of the schizophrenia prodrome, specifically risk factors, intervening variables and markers associated with the onset of psychosis. The goals of the training and research plan are integrated around the hypothesis that the neural diathesis of schizophrenia liability involves a vulnerability to develop psychosis in the context of psychosocial stress. Dr. Corcoran currently has experience in studying 1) the schizophrenia prodrome and 2) stress exposure and its correlates in schizophrenia. Under the sponsorship of Dr. Malaspina, and drawing upon resources at both NYSPI/Columbia and Hillside Hospital, Dr. Corcoran's training plan combines formal coursework and direct supervision with clinical research experience and training. Dr. Corcoran has established a prodromal research clinic at NYSPI, entitled the "Center of Prevention and Evaluation" (COPE). The training plan involves 1) clinical methodologies in the assessment of stress and the HPA axis in schizophrenia (Malaspina); 2) increased expertise in prodromal research and neuropsychology (Cornblatt); 3) data analysis in longitudinal studies (Begg) and 4) adolescent cognitive and social development (Kestenbuam). The research plan is a prospective cohort study of prodromal patients that employs clinical methodologies that probe HPA axis function, prodromal symptoms, and psychosocial stress exposure. The hypotheses are that baseline stress-reactivity (stress reactive cortisol and impaired tolerance to normal stress) and intervening life events will increase risk for psychosis in prodromal patients. Important covariates are also evaluated, including cognition, early trauma, and medication and substance use. This study will provide the applicant with the knowledge and research experience necessary to apply for an R01 to further evaluate risk factors, mediators and markers of psychosis onset in prodromal patients.