Laboratory of Neuro Imaging and Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
Hum Brain Mapp. 2009 Nov;30(11):3783-94. doi: 10.1002/hbm.20806.
Dystrobrevin binding protein 1 (DTNBP1) has been identified as putative schizophrenia susceptibility gene, but it remains unknown whether polymorphisms relate to altered cerebral structure. We examined relationships between a previously implicated DTNBP1 risk variant [P1578] and global and segmented brain tissue volumes and regional cortical thickness in schizophrenia (n = 62; 24 risk carriers) and healthy subjects (n = 42; 11 risk carriers), across ethnic groups and within Caucasians. Schizophrenia patients showed similar brain volumes, but significantly reduced brain-size adjusted gray matter and CSF volumes and cortical thinning in a widespread neocortical distribution compared to controls. DTNBP1 risk was found associated with reduced brain volume, but not with tissue sub-compartments. Cortical thickness, which was weakly associated with brain size, showed regional variations in association with genetic risk, although effects were dominated by highly significant genotype by diagnosis interactions over broad areas of cortex. Risk status was found associated with regional cortical thinning in patients, particularly in temporal networks, but with thickness increases in controls. DTNBP1 effects for brain volume and cortical thickness appear driven by different neurobiological processes. Smaller brain volumes observed in risk carriers may relate to previously reported DTNBP1/cognitive function relationships irrespective of diagnosis. Regional cortical thinning in patient, but not in control risk carriers, may suggest that DTNBP1 interacts with other schizophrenia-related risk factors to affect laminar thickness. Alternatively, DTNBP1 may influence neural processes for which individuals with thicker cortex are less vulnerable. Although DTNBP1 relates to cortical thinning in schizophrenia, morphological changes in the disorder are influenced by additional genetic and/or environmental factors.
肌营养不良蛋白结合蛋白 1（DTNBP1）已被确定为潜在的精神分裂症易感基因，但尚不清楚其多态性是否与改变的大脑结构有关。我们研究了先前涉及的 DTNBP1 风险变异 [P1578] 与精神分裂症患者（n=62；24 名风险携带者）和健康受试者（n=42；11 名风险携带者）的大脑整体和分段组织体积以及皮质厚度之间的关系，跨越了种族群体，在白种人中也进行了研究。精神分裂症患者的脑容量相似，但与对照组相比，大脑大小调整后的灰质和 CSF 体积以及广泛的新皮质分布中的皮质变薄明显减少。DTNBP1 风险与脑体积减少有关，但与组织亚区无关。皮质厚度与大脑大小弱相关，与遗传风险相关的区域也存在差异，但在广泛的皮质区域，基因型与诊断的相互作用具有显著的主导作用。在患者中，风险状态与局部皮质变薄有关，特别是在颞叶网络中，但在对照组中与皮质厚度增加有关。DTNBP1 对脑体积和皮质厚度的影响似乎是由不同的神经生物学过程驱动的。风险携带者中观察到的较小脑容量可能与先前报道的 DTNBP1/认知功能关系有关，而与诊断无关。患者而非对照组风险携带者的局部皮质变薄可能表明 DTNBP1 与其他精神分裂症相关风险因素相互作用，从而影响层厚度。或者，DTNBP1 可能影响皮层较厚的个体不易受到影响的神经过程。尽管 DTNBP1 与精神分裂症中的皮质变薄有关，但该疾病的形态变化还受到其他遗传和/或环境因素的影响。
