Department of Psychology, Institute of Psychiatry, King's College London, 103 Denmark Hill, London, UK.
Neuroimage. 2010 Jan 1;49(1):817-22. doi: 10.1016/j.neuroimage.2009.07.030. Epub 2009 Jul 22.
Schizophrenia is a neurodevelopmental disorder, and risk genes are thought to act through disruption of brain development. Several genetic studies have identified dystrobrevin binding protein 1 (DTNBP1, also known as dysbindin) as a potential susceptibility gene for schizophrenia, but its impact on brain function is poorly understood. It has been proposed that DTNBP1 may be associated with differences in visual processing. To test this, we examined the impact on visual processing in 61 healthy children aged 10-12 years of a genetic variant in DTNBP1 (rs2619538) that was common to all schizophrenia associated haplotypes in an earlier UK-Irish study. We tested the hypothesis that carriers of the risk allele would show altered occipital cortical function relative to noncarriers. Functional Magnetic Resonance Imaging (fMRI) was used to measure brain responses during a visual matching task. The data were analysed using statistical parametric mapping and statistical inferences were made at p<0.05 (corrected for multiple comparisons). Relative to noncarriers, carriers of the risk allele had greater activation in the lingual, fusiform gyrus and inferior occipital gyri. In these regions DTNBP1 genotype accounted for 19%, 20% and 14% of the inter-individual variance, respectively. Our results suggest that that genetic variation in DTNBP1 is associated with differences in the function of brain areas that mediate visual processing, and that these effects are evident in young children. These findings are consistent with the notion that the DTNBP1 gene influences brain development and can thereby modulate vulnerability to schizophrenia.
精神分裂症是一种神经发育障碍，风险基因被认为通过破坏大脑发育起作用。几项遗传研究已经确定了桥粒结合蛋白 1（DTNBP1，也称为 dysbindin）是精神分裂症的一个潜在易感基因，但它对大脑功能的影响知之甚少。有人提出 DTNBP1 可能与视觉处理的差异有关。为了检验这一点，我们研究了在 61 名年龄在 10-12 岁的健康儿童中，一种常见于早期英国-爱尔兰研究中所有与精神分裂症相关单体型的 DTNBP1 （rs2619538）遗传变异对视觉处理的影响。我们检验了这样一个假设，即风险等位基因的携带者相对于非携带者会表现出枕叶皮质功能的改变。功能磁共振成像（fMRI）用于测量视觉匹配任务期间的大脑反应。使用统计参数映射分析数据，并在 p<0.05 （校正多重比较）时进行统计推断。与非携带者相比，风险等位基因的携带者在舌回、梭状回和枕下回的激活程度更高。在这些区域，DTNBP1 基因型分别解释了个体间变异的 19%、20%和 14%。我们的结果表明，DTNBP1 中的遗传变异与介导视觉处理的大脑区域功能的差异有关，这些影响在幼儿中就很明显。这些发现与 DTNBP1 基因影响大脑发育并因此调节精神分裂症易感性的观点一致。
