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. 2025 Jul 25:16:1589040.
doi: 10.3389/fpsyt.2025.1589040. eCollection 2025.

Structural brain alterations in patients with anxious depression: evidence from the REST-meta-MDD project

Songhao Hu #  1   2 , Li Zhu #  1   2 , Xiang-Yang Zhang  1
Affiliations

Structural brain alterations in patients with anxious depression: evidence from the REST-meta-MDD project

Songhao Hu et al. Front Psychiatry. .

Abstract

Background: Anxious depression (AD) is a clinically significant subtype of major depressive disorder (MDD) characterized by prominent anxiety symptoms. Emerging neuroimaging evidence shows that AD patients have significantly altered brain structure. This study aimed to identify reliable neuroimaging biomarkers for AD in a Chinese cohort.

Methods: Participants were recruited from the REST-meta-MDD project, including 178 MDD patients and 89 healthy controls. MDD patients were stratified into 89 patients with AD and 89 with non-anxious depression (NAD). Voxel-based morphometry (VBM) was used to quantify gray matter volume (GMV) using T1-weighted images. Depressive and anxiety symptoms were assessed using the Hamilton Depression Rating Scale (HAMD-17) and the Hamilton Anxiety Rating Scale (HAMA-14). Structural covariance (SC) analysis was employed to investigate coordinated morphological changes across brain regions. Additionally, a support vector regression (SVR) model was constructed to predict anxiety severity in MDD patients, with external validation performed in an independent dataset.

Results: In AD patients, significant increases in GMV were observed in the right precuneus (PCUN) and right superior parietal gyrus (SPG). Reduced SC was also found between the right PCUN and left anterior cingulate gyrus (ACG), as well as between the right PCUN and right angular gyrus (ANG). Additionally, SVR analysis demonstrated that the right PCUN GMV could effectively predict MDD patients' HAMA-14 scores (r = 0.477, MSE = 73.865), validated in an independent external dataset (r = 0.368, MSE = 100.961).

Conclusions: This study's findings indicate that brain structural abnormalities may be a crucial pathophysiological basis for AD.

Keywords: anxious depression; gray matter volume; major depressive disorder; structural covariance; support vector regression.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Brain regions showed significant differences in GMV among the AD, NAD, and HC groups, and their correlations with HAMA-14 scores. (B) Brain regions with significant GMV differences between AD and NAD groups, and their correlations with HAMA-14 scores. (C) Brain regions demonstrating significant GMV differences between AD and HC groups, and their correlations with HAMA-14 scores. PCUN, Precuneus; SPG, Superior parietal gyrus. The color bars indicate the t-value or F-value (voxel-p< 0.001, cluster-p< 0.05, FDR correction).
Figure 2
Figure 2
SC with significant differences between the AD group and the NAD group. SC, Structural covariance; PCUN, Precuneus; ACG, Anterior cingulate and paracingulate gyri; ANG, Angular gyrus.
Figure 3
Figure 3
Predictive efficacy of a support vector regression model based on the right PCUN-derived GMV for HAMA Scores. (A) Performance Evaluation in the primary datasets. (B) Performance Evaluation in the external validation datasets. PCUN = Precuneus.
Figure 4
Figure 4
Consensus features and their weight distribution in the support vector regression Model.
See this image and copyright information in PMC

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