Savitz J, Solms M, Ramesar R
MRC/UCT Human Genetics Research Unit, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
Genes Brain Behav. 2006 Jun;5(4):311-28. doi: 10.1111/j.1601-183X.2005.00163.x.
The important contribution of genetic factors to the development of cognition and intelligence is widely acknowledged, but identification of these genes has proven to be difficult. Given a variety of evidence implicating the prefrontal cortex and its dopaminergic circuits in cognition, most of the research conducted to date has focused on genes regulating dopaminergic function. Here we review the genetic association studies carried out on catechol-O-methyltransferase (COMT) and the dopamine receptor genes, D1, D2 and D4. In addition, the evidence implicating another promising candidate gene, brain-derived neurotrophic factor (BDNF) in neuropsychological function, is assessed. Both the COMT val158met polymorphism and the BDNF val66met variant appear to influence cognitive function, but the specific neurocognitive processes involved continue to be a matter of debate. Part of the difficulty is distinguishing between false positives, pleiotropy and the influence of a general intelligence factor, g. Also at issue is the complexity of the relevant neuromolecular pathways, which make the inference of simple causal relationships difficult. The implications of molecular genetic cognitive research for psychiatry are discussed in light of these data.
遗传因素对认知和智力发展的重要贡献已得到广泛认可，但事实证明，识别这些基因颇具难度。鉴于有各种证据表明前额叶皮质及其多巴胺能回路与认知有关，迄今为止开展的大多数研究都集中在调节多巴胺能功能的基因上。在此，我们综述了针对儿茶酚-O-甲基转移酶（COMT）以及多巴胺受体基因D1、D2和D4所进行的基因关联研究。此外，还评估了另一个有前景的候选基因——脑源性神经营养因子（BDNF）与神经心理功能有关的证据。COMT基因的val158met多态性和BDNF基因的val66met变体似乎都影响认知功能，但其中涉及的具体神经认知过程仍是一个有争议的问题。部分困难在于区分假阳性、多效性以及一般智力因素g的影响。同样存在争议的是相关神经分子途径的复杂性，这使得推断简单的因果关系变得困难。鉴于这些数据，我们讨论了分子遗传学认知研究对精神病学的意义。
