Department of Psychiatry and Psychotherapy, Jena University Hospital, Germany.
Institute of Human Genetics, University of Bonn, Germany.
Psychol Med. 2014 Mar;44(4):811-20. doi: 10.1017/S0033291713001414.
Recent studies have provided strong evidence that variation in the gene neurocan (NCAN, rs1064395) is a common risk factor for bipolar disorder (BD) and schizophrenia. However, the possible relevance of NCAN variation to disease mechanisms in the human brain has not yet been explored. Thus, to identify a putative pathomechanism, we tested whether the risk allele has an influence on cortical thickness and folding in a well-characterized sample of patients with schizophrenia and healthy controls.
Sixty-three patients and 65 controls underwent T1-weighted magnetic resonance imaging (MRI) and were genotyped for the single nucleotide polymorphism (SNP) rs1064395. Folding and thickness were analysed on a node-by-node basis using a surface-based approach (FreeSurfer).
In patients, NCAN risk status (defined by AA and AG carriers) was found to be associated with higher folding in the right lateral occipital region and at a trend level for the left dorsolateral prefrontal cortex. Controls did not show any association (p > 0.05). For cortical thickness, there was no significant effect in either patients or controls.
This study is the first to describe an effect of the NCAN risk variant on brain structure. Our data show that the NCAN risk allele influences cortical folding in the occipital and prefrontal cortex, which may establish disease susceptibility during neurodevelopment. The findings suggest that NCAN is involved in visual processing and top-down cognitive functioning. Both major cognitive processes are known to be disturbed in schizophrenia. Moreover, our study reveals new evidence for a specific genetic influence on local cortical folding in schizophrenia.
最近的研究提供了强有力的证据，表明神经粘蛋白（NCAN，rs1064395）基因的变异是双相情感障碍（BD）和精神分裂症的常见风险因素。然而，NCAN 变异与人类大脑疾病机制的可能相关性尚未得到探索。因此，为了确定一个可能的发病机制，我们测试了风险等位基因是否对精神分裂症患者和健康对照者的特征明确的样本中的皮质厚度和折叠有影响。
63 名患者和 65 名对照者接受了 T1 加权磁共振成像（MRI）检查，并对单核苷酸多态性（SNP）rs1064395 进行了基因分型。使用基于表面的方法（FreeSurfer），在节点基础上分析折叠和厚度。
在患者中，NCAN 风险状态（由 AA 和 AG 携带者定义）与右侧外侧枕叶区域的折叠增加有关，而在左侧背外侧前额叶皮层则呈趋势水平。对照组没有发现任何关联（p>0.05）。对于皮质厚度，无论是患者还是对照组，都没有显著影响。
本研究首次描述了 NCAN 风险变异对大脑结构的影响。我们的数据表明，NCAN 风险等位基因影响枕叶和前额叶皮层的皮质折叠，这可能在神经发育过程中建立疾病易感性。研究结果表明，NCAN 参与视觉处理和自上而下的认知功能。这两个主要的认知过程在精神分裂症中都被认为是紊乱的。此外，我们的研究为精神分裂症中局部皮质折叠的特定遗传影响提供了新的证据。
