Centre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Pharmacology, University of Toronto, Toronto, Canada.
Centre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada.
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Jan 10;104:110071. doi: 10.1016/j.pnpbp.2020.110071. Epub 2020 Aug 13.
Investigate the effects of CACNA1C rs1006737 on cortical and subcortical neurostructural phenotypes in Caucasian bipolar disorder (BD) and healthy control (HC) adolescents.
Seventy-one adolescents (14-20 years; 38BD, 33HC) underwent 3-Tesla Magnetic Resonance Imaging (MRI). Region of interest (ROI) and vertex-wise analyses examined cortical volume, surface area (SA), and thickness, as well as subcortical volume. ROIs included the ventromedial prefrontal cortex (vmPFC), ventrolateral prefrontal cortex (vlPFC), anterior cingulate cortex (ACC), putamen, and amygdala. General linear models included main effects of diagnosis and rs1006737, and an interaction term, controlling for age, sex, and total intracranial volume.
Vertex-wise analysis found significant BD-by-rs1006737 interactions for prefrontal and occipital regions such that BD A-carriers were found to have greater SA relative to BD non-carriers, while HC A-carriers had reduced SA relative to HC non-carriers. ROI analysis found an interaction in the ACC such that BD A-carriers were found to have greater SA relative to BD non-carriers, while no significant difference was found in HCs. Main effects of rs1006737 were also found on ACC SA from ROI analysis, and occipital SA from vertex-wise analysis, such that A-carriers had larger SA relative to non-carriers in both of these regions.
The current study identified neurostructural intermediate phenotypes relevant to the impact of CACNA1C rs1006737 on adolescent BD. Further investigation is warranted into the neurofunctional and neurocognitive relevance of rs1006737 associations with BD-specific elevations in regional SA.
研究 CACNA1C rs1006737 对高加索裔双相情感障碍（BD）和健康对照（HC）青少年皮质和皮质下神经结构表型的影响。
71 名青少年（14-20 岁；38 名 BD，33 名 HC）接受了 3-Tesla 磁共振成像（MRI）检查。感兴趣区（ROI）和顶点分析检查了皮质体积、表面积（SA）和厚度以及皮质下体积。ROI 包括腹内侧前额叶皮质（vmPFC）、腹外侧前额叶皮质（vlPFC）、前扣带皮质（ACC）、壳核和杏仁核。一般线性模型包括诊断和 rs1006737 的主效应，以及年龄、性别和总颅内体积的交互项。
顶点分析发现，前额叶和枕叶区域存在显著的 BD-rs1006737 相互作用，即 BD A 携带者的 SA 相对于 BD 非携带者增加，而 HC A 携带者的 SA 相对于 HC 非携带者减少。ROI 分析发现，ACC 存在交互作用，即 BD A 携带者的 SA 相对于 BD 非携带者增加，而 HC 中未发现显著差异。ROI 分析还发现，ACC 的 SA 存在 rs1006737 的主效应，而顶点分析发现，枕叶的 SA 也存在 rs1006737 的主效应，即这两个区域的 A 携带者的 SA 相对于非携带者更大。
本研究确定了与 CACNA1C rs1006737 对青少年 BD 影响相关的神经结构中间表型。进一步研究 rs1006737 与 BD 特异性的区域 SA 升高相关的神经功能和神经认知相关性是有必要的。
