Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Sep 24:20:1781-1796.
doi: 10.2147/NDT.S468290. eCollection 2024.

The Effects of Variation in the GABAA Receptor Gene on Anxious Depression are Mediated by the Functional Connectivity Between the Amygdala and Middle Frontal Gyrus

Juan Qiao  1   2 , Shiwan Tao  2 , Yurong Sun  3   4 , Jiabo Shi  2   5 , Yu Chen  2   5 , Shui Tian  3   4 , Zhijian Yao  2   5 , Qing Lu  3   4
Affiliations

The Effects of Variation in the GABAA Receptor Gene on Anxious Depression are Mediated by the Functional Connectivity Between the Amygdala and Middle Frontal Gyrus

Juan Qiao et al. Neuropsychiatr Dis Treat. .

Abstract

Background: γ-aminobutyric acid (GABA) and its main receptor, the GABAA 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 GABAA receptors. Although the GABAergic deficit hypothesis of MDD is generally accepted, few studies have demonstrated how GABAA receptor gene polymorphisms affect the functions of specific brain regions, in particular, the amygdala and the DLPFC.

Methods: 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 GABAA 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, GABAA 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 GABAA receptor gene MGPS and AD clinical features.

Results: Compared with the NAD group, the AD group had a higher GABAA 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 GABAA receptor MGPS and anxiety/somatic symptoms in patients with AD.

Conclusion: The decreased FC between the right MFG and right CM subregion mediates the association between GABAA receptor MGPS and AD.

Keywords: GABAA receptor; amygdala subregion; anxious depression; dorsolateral prefrontal cortex; multi-locus genetic profile scores.

PubMed Disclaimer

Conflict of interest statement

The authors declare that this study was performed without any business or financial relationships that could be interpreted as potential conflicts of interest.

Figures

Figure 1
Figure 1
The amygdala subregions.
Figure 2
Figure 2
The ROI of the dorsolateral prefrontal cortex (DLPFC).
Figure 3
Figure 3
Comparison of the MGPS among the three groups.
Figure 4
Figure 4
Correlation analysis between the MGPS and the anxiety/somatic factor in the AD group.
Figure 5
Figure 5
Correlation analysis between the MGPS and FC in the anxious depression group.
Figure 6
Figure 6
Correlation analysis between FC and clinical symptoms.
Figure 7
Figure 7
Analysis of the mediating effect in patients with anxious depression.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Kessler RC, Sampson NA, Berglund P. et al. Anxious and non-anxious major depressive disorder in the World Health Organization World Mental Health Surveys. Epidemiol Psychiatr Sci. 2015;24(3):210–226. doi:10.1017/S2045796015000189 - DOI - PMC - PubMed
    1. Bui E, Fava M. From depression to anxiety, and back. Acta Psychiatr Scand. 2017;136:341–342. doi:10.1111/acps.12801 - DOI - PubMed
    1. Fava M, Rush AJ, Alpert JE, et al. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry. 2008;165(3):342–351. doi:10.1176/appi.ajp.2007.06111868 - DOI - PubMed
    1. Ionescu DF, Niciu MJ, Richards EM, et al. Pharmacologic treatment of dimensional anxious depression: a review. Prim Care Companion CNS Disord. 2014;16(3):27099. doi:10.4088/PCC.13r01621 - DOI - PMC - PubMed
    1. Seo HJ, Jung YE, Kim TS, et al. Distinctive clinical characteristics and suicidal tendencies of patients with anxious depression. J Nerv Ment Dis. 2011;199(1):42–48. doi:10.1097/NMD.0b013e3182043b60 - DOI - PubMed

LinkOut - more resources