Farmer Anne, Elkin Amanda, McGuffin Peter
MRC SGDP Centre, Institute of Psychiatry, Camberwell, London, UK.
Curr Opin Psychiatry. 2007 Jan;20(1):8-12. doi: 10.1097/YCO.0b013e3280117722.
Molecular genetic studies of bipolar affective disorder are beginning to show some positive and reproducible findings. The most relevant of these will be reviewed.
Obtaining consistent findings from whole genome scans has been hampered by small sample sizes and phenotypic heterogeneity. Recently, there have been concerted efforts to overcome these problems by combining data for meta-analysis. What has become increasingly clear is that several regions that are likely to contain genes contributing to bipolar affective disorder are also relevant to schizophrenia, a finding supported by recent twin data. Studies to date have implicated the D-amino acid oxidase activator complex (also known as G72/G30), disrupted in schizophrenia-1 and neuregulin, and have pointed to several promising linkage regions in which the genes have not yet been identified. In addition, there is some evidence to support the involvement of genetic variants in catechol-o-methyl transferase and brain-derived neurotrophic factor in the aetiology of bipolar affective disorder.
Molecular genetic research in bipolar affective disorder may lead to the development of new diagnostic paradigms for classifying the psychoses and affective states. In addition, determining the functional significance of the susceptibility genes will pave the way for enhanced diagnostic accuracy and improved treatments.
双相情感障碍的分子遗传学研究开始展现出一些积极且可重复的结果。本文将对其中最相关的结果进行综述。
全基因组扫描结果的一致性受到样本量小和表型异质性的阻碍。最近,人们通过整合数据进行荟萃分析,共同努力克服这些问题。越来越明确的是,几个可能包含导致双相情感障碍基因的区域也与精神分裂症相关,这一发现得到了近期双胞胎数据的支持。迄今为止的研究表明,D-氨基酸氧化酶激活复合物(也称为G72/G30)、精神分裂症相关基因-1和神经调节蛋白与双相情感障碍有关,并指出了几个有希望的连锁区域,但其中的基因尚未确定。此外,有证据支持儿茶酚-O-甲基转移酶和脑源性神经营养因子的遗传变异参与双相情感障碍的病因学。
双相情感障碍的分子遗传学研究可能会带来新的诊断模式,用于对精神病和情感状态进行分类。此外,确定易感基因的功能意义将为提高诊断准确性和改进治疗方法铺平道路。