Nieratschker Vanessa, Nöthen Markus M, Rietschel Marcella
Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim, Germany.
Front Behav Neurosci. 2010 May 11;4:23. doi: 10.3389/fnbeh.2010.00023. eCollection 2010.
Schizophrenia is a highly heritable disorder, but the identification of specific genes has proven to be a difficult endeavor. Genes involved in the dopaminergic system are considered to be major candidates since the "dopamine hypothesis" of impairment in dopaminergic neurotransmission is one of the most widely accepted hypotheses of the etiology of schizophrenia. The overall findings from candidate studies do provide some support for the "dopamine hypothesis." However, results from the first systematic genome-wide association (GWA) studies have implicated variants within ZNF804A, NRGN, TCF4, and variants in the MHC region on chromosome 6p22.1. Although these genes may not immediately impact on dopaminergic neurotransmission, it remains possible that downstream impairments in dopaminergic function are caused. Furthermore, only a very small fraction of all truly associated genetic variants have been detected and many more associated variants will be identified in the future by GWA studies and alternative approaches. The results of these studies may allow a more comprehensive re-evaluation of the dopamine hypothesis.
精神分裂症是一种高度可遗传的疾病，但已证明识别特定基因是一项艰巨的任务。由于多巴胺能神经传递受损的“多巴胺假说”是精神分裂症病因学中最广泛接受的假说之一，因此参与多巴胺能系统的基因被认为是主要候选基因。候选研究的总体结果确实为“多巴胺假说”提供了一些支持。然而，首批全基因组关联（GWA）系统研究的结果表明，锌指蛋白804A（ZNF804A）、神经调节蛋白（NRGN）、转录因子4（TCF4）以及6号染色体p22.1区域主要组织相容性复合体（MHC）中的变异体与精神分裂症有关。尽管这些基因可能不会立即影响多巴胺能神经传递，但仍有可能导致多巴胺能功能的下游损伤。此外，在所有真正相关的基因变异中，目前仅检测到极小一部分，未来通过全基因组关联研究和其他方法将识别出更多相关变异体。这些研究结果可能会使人们对多巴胺假说进行更全面的重新评估。
