Soeiro-de-Souza M G, Lafer B, Moreno R A, Nery F G, Chile T, Chaim K, da Costa Leite C, Machado-Vieira R, Otaduy M C G, Vallada H
Mood Disorders Unit (GRUDA), Department of Psychiatry, Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil.
Genetics and Pharmacogenetics Unit (PROGENE), Department of Psychiatry, Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil.
Transl Psychiatry. 2017 Apr 11;7(4):e1086. doi: 10.1038/tp.2017.57.
Calcium channels control the inflow of calcium ions into cells and are involved in diverse cellular functions. The CACNA1C gene polymorphism rs1006737 A allele has been strongly associated with increased risk for bipolar disorder (BD) and with modulation of brain morphology. The medial prefrontal cortex (mPFC) has been widely associated with mood regulation in BD, but the role of this CACNA1C polymorphism in mPFC morphology and brain aging has yet to be elucidated. One hundred seventeen euthymic BD type I subjects were genotyped for CACNA1C rs1006737 and underwent 3 T three-dimensional structural magnetic resonance imaging scans to determine cortical thickness of mPFC components (superior frontal cortex (sFC), medial orbitofrontal cortex (mOFC), caudal anterior cingulate cortex (cACC) and rostral anterior cingulate cortex (rACC)). Carriers of the CACNA1C allele A exhibited greater left mOFC thickness compared to non-carriers. Moreover, CACNA1C A carriers showed age-related cortical thinning of the left cACC, whereas among A non-carriers there was not an effect of age on left cACC cortical thinning. In the sFC, mOFC and rACC (left or right), a negative correlation was observed between age and cortical thickness, regardless of CACNA1C rs1006737 A status. Further studies investigating the direct link between cortical thickness, calcium channel function, apoptosis mechanism and their underlying relationship with aging-associated cognitive decline in BD are warranted.
钙通道控制钙离子流入细胞，并参与多种细胞功能。CACNA1C基因多态性rs1006737的A等位基因与双相情感障碍（BD）风险增加以及脑形态调节密切相关。内侧前额叶皮质（mPFC）在BD的情绪调节中具有广泛联系，但该CACNA1C多态性在mPFC形态和脑老化中的作用尚待阐明。对117名处于缓解期的I型BD患者进行CACNA1C rs1006737基因分型，并进行3T三维结构磁共振成像扫描，以确定mPFC各部分（额上皮质（sFC）、内侧眶额皮质（mOFC）、尾侧前扣带回皮质（cACC）和嘴侧前扣带回皮质（rACC））的皮质厚度。与非携带者相比，CACNA1C等位基因A的携带者左侧mOFC厚度更大。此外，CACNA1C A携带者左侧cACC出现与年龄相关的皮质变薄，而在A非携带者中，年龄对左侧cACC皮质变薄没有影响。在sFC、mOFC和rACC（左侧或右侧）中，无论CACNA1C rs1006737 A状态如何，年龄与皮质厚度之间均存在负相关。有必要进一步研究皮质厚度、钙通道功能、凋亡机制之间的直接联系以及它们与BD中与衰老相关的认知衰退的潜在关系。
