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CACNB2 rs11013860 多态性与首发躁狂的双相情感障碍患者前额叶皮层厚度相关。

CACNB2 rs11013860 polymorphism correlates of prefrontal cortex thickness in bipolar patients with first-episode mania.

机构信息

Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou HuiAi Hospital, Guangzhou, Guangdong, PR China.

Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada.

出版信息

J Affect Disord. 2020 May 1;268:82-87. doi: 10.1016/j.jad.2020.02.007. Epub 2020 Feb 3.

Abstract

BACKGROUND

The β2 subunit of the voltage-gated l-type calcium channel gene(CACNB2) rs11013860 polymorphism is a putative genetic susceptibility marker for bipolar disorder (BD). However, the neural effects of CACNB2 rs11013860 in BD are largely unknown.

METHODS

Forty-six bipolar patients with first-episode mania and eighty-three healthy controls (HC) were genotyped for CACNB2 rs11013860 and were scanned with a 3.0 Tesla structural magnetic resonance imaging system to measure cortical thickness of prefrontal cortex (PFC) components (superior frontal cortex, orbitofrontal cortex, middle and inferior frontal gyri).

RESULTS

Cortical thickness was thinner in patients on all PFC measurements compared to HC (p < 0.050). Moreover, we found a significant interaction between CACNB2 genotype and diagnosis for the right superior frontal cortical thickness (F = 8.190, p = 0.040). Bonferroni corrected post-hoc tests revealed that, in CACNB2 A-allele carriers, patients displayed thinner superior frontal thickness compared to HC (p < 0.001). In patients, CACNB2 A-allele carriers also exhibited reduced superior frontal thickness compared to CACNB2 CC-allele carriers (p = 0.016).

LIMITATIONS

Lithium treatment may influence our results, and the sample size in our study is relatively small.

CONCLUSIONS

Our results suggest that the CACNB2 rs11013860 might impact PFC thickness in patients with first-episode mania. These findings provide evidence to support CACNB2 rs11013860 involvement in the emotion-processing neural circuitry abnormality in the early stage of BD, which will ultimately contribute to revealing the link between the variation in calcium channel genes and the neuropathological mechanism of BD.

摘要

背景

电压门控 L 型钙通道基因(CACNB2)rs11013860 多态性β2 亚基是双相障碍(BD)的潜在遗传易感性标志物。然而,CACNB2 rs11013860 在 BD 中的神经效应在很大程度上尚不清楚。

方法

46 例首发躁狂的双相患者和 83 名健康对照者(HC)进行了 CACNB2 rs11013860 基因分型,并使用 3.0 特斯拉结构磁共振成像系统对前额叶皮质(PFC)成分(额上回、眶额回、中回和下回)的皮质厚度进行了测量。

结果

与 HC 相比,所有 PFC 测量的患者皮质厚度均较薄(p<0.050)。此外,我们发现 CACNB2 基因型与诊断之间存在右额上皮质厚度的显著交互作用(F=8.190,p=0.040)。Bonferroni 校正后检验显示,在 CACNB2 A 等位基因携带者中,患者的额上回皮质厚度较 HC 薄(p<0.001)。在患者中,CACNB2 A 等位基因携带者的额上回皮质厚度也较 CACNB2 CC 等位基因携带者薄(p=0.016)。

局限性

锂治疗可能会影响我们的结果,而且我们研究的样本量相对较小。

结论

我们的结果表明,CACNB2 rs11013860 可能会影响首发躁狂患者的 PFC 厚度。这些发现为 CACNB2 rs11013860 参与 BD 早期情绪处理神经回路异常提供了证据,这将最终有助于揭示钙通道基因变异与 BD 神经病理学机制之间的联系。

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