Identifying & Characterizing Prodromal Schizophrenia

描述(由申请人提供)：本修订申请导师研究科学家发展奖(K01)提出了一个计划，候选人继续培训和研究精神分裂症前驱症状的评估。培训和研究计划的目标是围绕这样一个假设整合的，即减弱的阴性症状代表着精神分裂症的一个关键风险领域，该领域在表型和内表型水平上都可以与减弱的阳性症状分离。研究将利用自我报告问卷测量和功能磁共振成像(FMRI)，候选人将在培训计划中发展技能，成为一名在精神分裂症谱系障碍发展研究的前沿开展工作的独立调查员。培训计划将提高候选人在两个领域的技能，这两个领域是精神分裂症高危对象进行最先进研究所必需的：1)精神病和亚精神状态的临床评估，包括现象学、精神病理学中的发展问题和心理计量学；2)功能神经成像评估，包括神经生理学、神经发育和功能磁共振任务设计和统计分析。此外，候选人将接受涉及可能有严重精神疾病风险的青少年受试者研究的伦理问题方面的培训。对于每个领域，都有当地的首席顾问，他们将定期监督候选人的培训和研究进展，以及咨询和访问与前兆研究相关的领先实验室。候选人将由总体导师、扎克希尔赛德医院高风险研究部主任芭芭拉·康布拉特博士密切监督。研究计划包括一项综合上述两个评估领域的研究。研究将与进入山坡识别和预防(RAP)计划的青少年受试者进行，这是一项由联邦资助的精神分裂症风险研究。RAP项目的初步研究导致了一个假设的前驱症状神经发育模型，在该模型中，认知缺陷(如注意力障碍)和减弱的负面症状(如社交隔离)先于减弱的阳性症状和精神病发作。这一假设将通过使用分裂型人格问卷(SPQ)对RAP患者和寻求治疗的对照对象进行检验。验证性因素分析将被用来确定阳性和阴性症状域，这可能会区分RAP亚组之间以及RAP患者与非RAP患者之间的差别。将使用新开发的和以前设计的fMRI任务来检验这些症状领域的神经功能相关性，以检验以下假设：阴性症状的减弱与腹侧前额叶皮质的功能障碍有关，而阳性症状的减弱与前额叶背侧皮质的功能障碍有关。这项研究将为应聘者提供申请R01所需的知识和研究经验，以从神经发育的角度扩展这项研究。

DESCRIPTION (provided by applicant): This revised application for a Mentored Research Scientist Development Award (K01) presents a plan for the candidate to pursue training and research in the assessment of the schizophrenia prodrome. The goals of the training and research plan are integrated around the hypothesis that attenuated negative symptoms represent a critical domain of risk for schizophrenia that is dissociable from attenuated positive symptoms at both the phenotypic and endophenotypic level. Research will utilize self-report questionnaire measures and functional magnetic resonance imaging (fMRI), with the candidate developing skills in the training program to become an independent investigator operating at the cutting edge of research in the development of schizophrenia spectrum disorders. The training plan would increase the candidate's skills in two domains necessary for state-of-the art research in subjects at risk for schizophrenia: 1) clinical assessment of psychosis and sub-psychotic states, including phenomenology, developmental issues in psychopathology, and psychometrics; and 2) functional neuroimaging assessment, including neurophysiology, neurodevelopment, and fMRI task design and statistical analysis. Additionally, the candidate will be trained in ethical issues of research involving adolescent subjects who may be at risk for severe mental illness. For each domain, there are local lead advisors who will provide regular supervision of the candidate's training and research progress, as well as consultation with and visits to leading laboratories relevant to prodromal research. The candidate will be closely supervised by the overall mentor, Dr. Barbara Cornblatt, Director of the Division of High Risk Studies at The Zucker Hillside Hospital. The research plan consists of a study integrating the two assessment domains above. Research will be conducted with adolescent subjects entering the Hillside Recognition and Prevention (RAP) Program, a federally funded study of risk for schizophrenia. Preliminary research in the RAP Program has led to a hypothesized neurodevelopmental model of the prodrome, in which cognitive deficits (such as attentional impairment) and attenuated negative symptoms (such as social isolation) precede onset of attenuated positive symptoms and psychosis. This hypothesis will be tested by administering the schizotypal personality questionnaire (SPQ) to RAP patients and treatment-seeking comparison subjects. Confirmatory factor analysis will be performed to identify positive and negative symptoms domains, which may differentiate RAP subgroups from each other and from non-RAP patients. Neurofunctional correlates of these symptom domains will be examined using both newly-developed and previously designed fMRI tasks to test the hypothesis that attenuated negative symptoms are related to dysfunction of the ventral prefrontal cortex, and attenuated positive symptoms are related to dysfunction of dorsal prefrontal cortex. This study will provide the candidate with the knowledge and research experience necessary to apply for an R01 to expand upon this research from a neurodevelopmental perspective.