COMT genotype and response to cognitive remediation in schizophrenia

描述（由申请人提供）：本项目将收集试点数据，以探讨儿茶酚-O-甲基转移酶（COMT）Val 158/108 Met基因型与对曼哈顿精神病中心（一家拥有350张床位的三级护理精神病医院）住院的慢性精神分裂症患者进行12周计算机神经认知康复（CRT）的反应之间的关系。有一个广泛的共识，认知缺陷在精神分裂症的发病机制和预后中起着至关重要的作用。认知障碍的有效治疗有可能改善整体疾病结果。神经认知和功能性神经影像学研究一直显示精神分裂症患者的前额皮质异常。COMT基因在一系列健康脑功能和脑疾病（包括精神分裂症）中被认为是重要的神经系统中功能性表达。已显示COMT Met等位基因与较低活性形式的COMT相关，并且在神经认知测试中具有更好的表现，而COMT瓦尔等位基因与较差的执行认知相关。本研究旨在探讨慢性精神分裂症患者COMT基因多态性与CRT靶向治疗的视觉空间加工、注意力和认知灵活性的关系。我们假设COMT Met等位基因与CRT后更好的神经认知表现相关，而COMT瓦尔等位基因与这些区域神经认知功能的较少增益相关。此外，我们将评估基因型对不同神经认知领域的影响，以更有力地描述与COMT多态性相关的神经认知表型。本提案旨在获得资金，对研究样本进行基因分型，并进行拟议的分析。我们不要求资金进行CRT，也不要求资金进行神经认知评估和精神病理学评估，这些评估由医院提供。筛选后，142例受试者将接受CRT治疗，每周3小时，持续12周。将在基线和终点（第12周）时对受试者进行标准化神经心理学评估。接受CRT的患者将提供唾液样本进行遗传分析。基因分型将由精神遗传学家赫伯特拉赫曼博士进行。考虑到精神分裂症脑病理生理的多样性和复杂性，阐明COMT多态性与神经认知康复治疗水平的可能关系可能对患者定制认知治疗有价值。考虑到精神分裂症脑病理生理的多样性和复杂性，阐明COMT多态性与神经认知康复治疗水平的可能关系可能对患者定制认知治疗有价值。

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.