Effect of Genetic Variant in BICC1 on Functional and Structural Brain Changes in Depression
Effect of Genetic Variant in BICC1 on Functional and Structural Brain Changes in Depression
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DOI：
10.1038/npp.2012.158
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发表时间：
2012-08
影响因子：
7.6
通讯作者：
R. Bermingham;A. Carballedo;Danuta M Lisiecka;A. Fagan;D. Morris;C. Fahey;G. Donohoe;J. Meaney;M. Gill;T. Frodl
中科院分区：
文献类型：
--
作者：
R. Bermingham;A. Carballedo;Danuta M Lisiecka;A. Fagan;D. Morris;C. Fahey;G. Donohoe;J. Meaney;M. Gill;T. Frodl
基因和早期生活逆境(ELA)交互作用增加患严重抑郁障碍(MDD)的风险。最近的全基因组关联研究表明，双尾状C同源1基因(BICC1)单核苷酸多态的次要T等位基因对MDD具有保护作用。本研究的目的是研究BICC1的微小T等位基因是否对海马区结构的脑变化具有保护作用，它是否与情绪调节系统中脑功能活动的增加有关，以及ELA如何改变这种联系。对44例MDD患者和44例健康对照进行了情绪抑制任务的结构磁共振成像(MRI)和功能磁共振成像(FMRI)检查。对BICC1-1(Rs999845)基因进行单核苷酸多态性分析。与携带BICC1主要C等位基因纯合子的参与者相比，没有ELA病史且携带BICC1保护性T等位基因的患者和对照组的右侧海马体明显更大。然而，携带T等位基因的携带ELA的MDD患者与不携带ELA的MDD患者相比，海马头体积较小。功能磁共振成像显示，与携带主要C等位基因纯合子的患者和对照组相比，携带保护性T等位基因的患者和对照组激活情绪调节系统的程度显著更高(p<；0.05，家庭错误校正)。这些结果提示，BICC1的微小T等位基因对MDD及其已知的脑结构和功能改变具有保护作用。然而，在ELA并存的情况下，这种保护作用似乎消失了。
Genes and early-life adversity (ELA) interactively increase the risk of developing major depressive disorder (MDD). A recent genome-wide association study suggests that the minor T-allele of single-nucleotide polymorphisms in the bicaudal C homolog 1 gene (BICC1) has a protective role against MDD. The aims of the study were to investigate whether the minor T-allele of BICC1 is protective against hippocampal structural brain changes, whether it is associated with increased functional brain activity in the emotion regulation system, and how ELA would modify this association. Forty-four patients with MDD and 44 healthy controls were investigated using structural magnetic resonance imaging (MRI) and functional MRI with an emotion inhibition task. Analysis of a single-nucleotide polymorphism in the BICC1-1 (rs999845) gene was performed. Right hippocampal bodies of patients and controls without a history of ELA and who carry the protective T-allele of BICC1 were significantly larger compared with those participants homozygous for the major C-allele of BICC1. However, MDD patients with ELA, who carry the T-allele, had smaller hippocampal head volumes compared with MDD patients without ELA. FMRI showed that patients and controls carrying the protective T-allele of BICC1 activate the emotion regulation system significantly more compared with those participants homozygous for the major C-allele (p< 0.05, family wise error corrected). These results are suggestive that the minor T-allele of BICC1 has a protective role against MDD and its known structural and functional brain changes. However, this protective effect seems to be lost in the case of co-occurrence of ELA.