Qiao Juan, Tao Shiwan, Sun Yurong, Shi Jiabo, Chen Yu, Tian Shui, Yao Zhijian, Lu Qing
Department of Psychology, Xuzhou East Hospital Affiliated to Xuzhou Medical University, Xuzhou, People's Republic of China.
Department of Psychiatry, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
Neuropsychiatr Dis Treat. 2024 Sep 24;20:1781-1796. doi: 10.2147/NDT.S468290. eCollection 2024.
γ-aminobutyric acid (GABA) and its main receptor, the GABA receptor, are implicated in major depressive disorder (MDD). Anxious depression (AD) is deemed to be a primary subtype of MDD. The amygdala and the dorsolateral prefrontal cortex (DLPFC) are key brain regions involved in emotional regulation. These regions contain the most GABA receptors. Although the GABAergic deficit hypothesis of MDD is generally accepted, few studies have demonstrated how GABA receptor gene polymorphisms affect the functions of specific brain regions, in particular, the amygdala and the DLPFC.
The sample comprised 83 patients with AD, 70 patients with non-anxious depression (NAD), and 62 healthy controls (HC). All participants underwent genotyping for polymorphisms of GABA receptor subunit genes, followed by a resting-state fMRI scan. The HAMD-17 was used to evaluate the severity of MDD. ANOVA was performed to obtain the difference in the imaging data, GABA receptor multi-locus genetic profile scores (MGPS), and HAMD-17 scores among three groups, then the significant differences between AD and NAD groups were identified. Mediating effect analysis was used to explore the role of functional connectivity (FC) between the amygdala and DLPFC in the association between the GABA receptor gene MGPS and AD clinical features.
Compared with the NAD group, the AD group had a higher GABA receptor MGPS. AD patients exhibited a negative correlation between the MGPS and FC of the right centromedial (CM) subregion, and the right middle frontal gyrus (MFG). A negative correlation was also observed between the MGPS and anxiety/somatic symptoms. More importantly, the right CM and right MFG connectivity mediated the association between the GABA receptor MGPS and anxiety/somatic symptoms in patients with AD.
The decreased FC between the right MFG and right CM subregion mediates the association between GABA receptor MGPS and AD.
γ-氨基丁酸（GABA）及其主要受体GABA受体与重度抑郁症（MDD）有关。焦虑抑郁（AD）被认为是MDD的一种主要亚型。杏仁核和背外侧前额叶皮质（DLPFC）是参与情绪调节的关键脑区。这些区域含有最多的GABA受体。尽管MDD的GABA能缺陷假说已被普遍接受，但很少有研究表明GABA受体基因多态性如何影响特定脑区的功能，特别是杏仁核和DLPFC。
样本包括83例AD患者、70例非焦虑抑郁（NAD）患者和62名健康对照（HC）。所有参与者均接受GABA受体亚基基因多态性的基因分型，随后进行静息态功能磁共振成像扫描。采用汉密尔顿抑郁量表17项版（HAMD-17）评估MDD的严重程度。进行方差分析以获得三组之间成像数据、GABA受体多位点基因谱评分（MGPS）和HAMD-17评分的差异，然后确定AD组和NAD组之间的显著差异。采用中介效应分析探讨杏仁核与DLPFC之间的功能连接（FC）在GABA受体基因MGPS与AD临床特征关联中的作用。
与NAD组相比，AD组的GABA受体MGPS更高。AD患者的MGPS与右侧中央内侧（CM）亚区和右侧额中回（MFG）的FC呈负相关。MGPS与焦虑/躯体症状之间也观察到负相关。更重要的是，右侧CM和右侧MFG连接介导了AD患者GABA受体MGPS与焦虑/躯体症状之间的关联。
右侧MFG和右侧CM亚区之间FC的降低介导了GABA受体MGPS与AD之间的关联。
