COMT genotype and response to cognitive remediation in schizophrenia

描述(由申请人提供)：该项目将收集试点数据，以探索儿茶酚-O-甲基转移酶(COMT)Val158/108Met基因与曼哈顿精神病院住院的慢性精神分裂症患者接受为期12周的计算机化神经认知康复(CRT)的反应之间的关系。曼哈顿精神病学中心是一家拥有350个床位的三级护理精神病院。人们普遍认为，认知缺陷在精神分裂症的发病机制和预后中都起着至关重要的作用。认知障碍的有效治疗有可能改善总体疾病结局。神经认知和功能神经成像研究一直显示精神分裂症患者前额叶皮质异常。COMT基因在神经系统中有功能表达，被认为对一系列健康的大脑功能和包括精神分裂症在内的大脑疾病很重要。研究表明，COMT Met等位基因与COMT活性较低的形式有关，并且在神经认知测试中表现较好，而COMT Val等位基因与较差的执行认知能力有关。本研究将探讨慢性精神分裂症患者COMT基因多态性与CRT反应的关系。CRT针对视觉空间加工、注意力和认知灵活性。我们假设COMT Met等位基因将与CRT后更好的神经认知表现相关，而COMT Val等位基因将与这些区域神经认知功能的较低收益相关。此外，我们将评估不同神经认知域的基因效应，以更有力地描述与COMT多态相关的神经认知表型。本提案寻求获得资金，以便对研究样本进行基因分型，同时进行拟议的分析。我们没有要求资金进行CRT，也没有要求资金进行由医院提供的神经认知评估和精神病理评估。筛查后，142名受试者将接受为期12周的每周3小时的CRT。受试者将在基线和终点(第12周)接受标准化的神经心理学评估。接受CRT的患者将提供唾液样本进行基因分析。基因分型将由精神病遗传学家赫伯特·拉赫曼博士进行。鉴于精神分裂症患者大脑病理生理学的多样性和复杂性，阐明COMT基因多态与神经认知康复治疗中表现水平的可能关系，对于为患者定制认知治疗可能有价值。鉴于精神分裂症患者大脑病理生理学的多样性和复杂性，阐明COMT基因多态与神经认知康复治疗中表现水平的可能关系，对于为患者定制认知治疗可能有价值。

DESCRIPTION (provided by applicant): This project will collect pilot data to explore the relationship between catechol-O-methyltransferase (COMT) Val158/108Met genotype and response to a 12-week computerized neurocognitive rehabilitation (CRT) given to chronic schizophrenic patients hospitalized at Manhattan Psychiatric Center, a 350-bed tertiary care psychiatric hospital. There is a broad consensus that cognitive deficits play a crucial role in both the pathogenesis and prognosis of schizophrenia. Effective treatment of cognitive impairments has the potential to improve overall illness outcome. Neurocognitive and functional neuroimaging studies have consistently revealed abnormalities in prefrontal cortex in patients with schizophrenia. The COMT gene is functionally expressed in neural systems considered important in a range of healthy brain functions and brain disorders, including schizophrenia. The COMT Met allele has been shown to be associated with a lower activity form of COMT, and with better performance on neurocognitive tests, while the COMT Val allele is associated with poorer executive cognition. This study will investigate the relationship of COMT polymorphism in patients with chronic schizophrenia with the response to CRT targeting visuospatial processing, attention, and cognitive flexibility. We hypothesize that the COMT Met allele will be associated with better neurocognitive performance after CRT, while the COMT Val allele will be associated with lesser gains in neurocognitive functioning in these areas. In addition, we will assess the genotype effect on different neurocognitive domains to characterize the neurocognitive phenotype more robustly related to the COMT polymorphism. The present proposal seeks to obtain funds to conduct the genotyping of the study sample, together with the proposed analysis. We are not requesting funds to conduct the CRT, nor for the neurocognitive evaluations and psychopathological assessments, which are provided by the hospital. After screening, 142 subjects will receive CRT for 3 hours per week for 12 weeks. Subjects will be evaluated on a standardized battery of neuropsychological assessments at baseline and at endpoint (Week 12). Patients having received CRT will provide saliva samples for genetic analysis. Genotyping will be conducted by psychiatric geneticist Dr. Herbert Lachman. Given the diversity and complexity of brain pathophysiology in schizophrenia, elucidating the possible relationship of COMT polymorphism with the level of performance in a neurocognitive rehabilitation treatment may be valuable for customizing cognitive treatments for patients. Given the diversity and complexity of brain pathophysiology in schizophrenia, elucidating the possible relationship of COMT polymorphism with the level of performance in a neurocognitive rehabilitation treatment may be valuable for customizing cognitive treatments for patients.