Seidman Larry J, Wencel Heidi E
Neuropsychology Laboratory, Massachusetts Mental Health Center, 74 Fenwood Road, Boston, MA 02115, USA.
Curr Psychiatry Rep. 2003 Jun;5(2):135-44. doi: 10.1007/s11920-003-0030-4.
Schizophrenia is a highly heritable, neurobehavioral disorder; however, the mode of inheritance is complex, and linkage findings have been difficult to replicate. Some consistent linkage findings have emerged on chromosomes 1, 6, 8, 11, 13, 15, and 22. New methods are being developed for candidate gene identification, including the use of neurobiologic phenotypes observed in relatives of persons with schizophrenia. Neuroimaging studies of relatives implicate abnormal hippocampal structure and inefficient prefrontal network functioning, probably representing mild variants of the abnormalities observed in schizophrenia. These characteristics may represent stable markers of vulnerability to schizophrenia, because they are not confounded by effects of antipsychotic drugs or psychosis. Recent studies provide evidence for a small role of the catechol-O-methyltransferase gene on 22q, and the serotonin receptor transporter gene on 17q11-q12 in the development of schizophrenia. Linking genes and brain regions or networks is an important step in identification of the pathophysiology of schizophrenia.
精神分裂症是一种高度可遗传的神经行为障碍；然而，其遗传模式复杂，连锁研究结果难以重复。在1号、6号、8号、11号、13号、15号和22号染色体上已出现一些一致的连锁研究结果。目前正在开发用于识别候选基因的新方法，包括利用在精神分裂症患者亲属中观察到的神经生物学表型。对亲属的神经影像学研究表明海马结构异常和前额叶网络功能低效，这可能代表了在精神分裂症中观察到的异常的轻度变体。这些特征可能是易患精神分裂症的稳定标志物，因为它们不受抗精神病药物或精神病影响的干扰。最近的研究为22号染色体上的儿茶酚-O-甲基转移酶基因以及17号染色体q11-q12区域的5-羟色胺受体转运蛋白基因在精神分裂症发病中起的小作用提供了证据。将基因与脑区或神经网络联系起来是识别精神分裂症病理生理学的重要一步。
