Identifying & Characterizing Prodromal Schizophrenia

识别

• 批准号: 6717732
• 负责人: TODD LENCZ
• 金额: $ 13.28万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6717732
• 关键词: adolescence (12-20); behavioral /social science research tag; clinical research; cognition; developmental neurobiology; disease /disorder proneness /risk; functional magnetic resonance imaging; human subject; mental health epidemiology; neuroimaging; neurophysiology; pathologic process; patient oriented research; phenotype; prefrontal lobe /cortex; psychological tests; psychometrics; psychosis; questionnaires; schizophrenia

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.

描述（由申请人提供）：这份修订后的指导研究科学家发展奖（K01）申请提出了一项计划，供候选人在精神分裂症前驱症状评估中进行培训和研究。培训和研究计划的目标是围绕这样一个假设进行整合的，即减毒阴性症状代表了精神分裂症风险的一个关键领域，在表型和内表型水平上与减毒阳性症状无关。研究将利用自我报告问卷测量和功能性磁共振成像（fMRI），候选人在培训计划中发展技能，成为一名独立的调查员，在精神分裂症谱系障碍的发展研究中处于领先地位。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风险受试者最先进研究所必需的：1）精神病和亚精神病状态的临床评估，包括现象学，精神病理学中的发展问题和心理测量学; 2）功能性神经影像评估，包括神经生理学，神经发育和fMRI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的研究伦理问题的培训。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驱研究相关的领先实验室。候选人将由总导师芭芭拉·康布拉特博士密切监督，她是Zucker希尔赛德医院高风险研究部主任。研究计划包括一项综合上述两个评估领域的研究。研究将在参加希尔赛德识别和预防（RAP）项目的青少年受试者中进行，该项目是一项由联邦政府资助的精神分裂症风险研究。RAP计划的初步研究已经导致了前驱症状的假设神经发育模型，其中认知缺陷（如注意力障碍）和减弱的阴性症状（如社会孤立）先于减弱的阳性症状和精神病发作。将通过对RAP患者和寻求治疗的对照受试者进行典型人格问卷（SPQ）来检验这一假设。将进行炎症因子分析，以确定阳性和阴性症状领域，这可能会区分RAP亚组彼此和非RAP患者。这些症状域的神经功能相关性将检查使用新开发的和以前设计的功能磁共振成像任务，以检验假设，衰减的阴性症状与腹侧前额叶皮层功能障碍，衰减的阳性症状与背侧前额叶皮层功能障碍。这项研究将为候选人提供申请R01所需的知识和研究经验，以便从神经发育的角度扩展这项研究。