Gray matter volume alterations in generalized anxiety disorder and major depressive disorder

Generalized anxiety disorder (GAD) and major depressive disorder (MDD) are highly comorbid and clinically overlapping, but their shared and differential structural brain alterations remain unclear. This study investigated gray matter volume (GMV) alterations in GAD and MDD using voxel-based morphometry (VBM).

A total of 168 right-handed participants, including 42 patients with GAD, 43 patients with MDD, and 83 healthy controls (HCs), underwent high-resolution T1-weighted MRI. Whole-brain VBM analyses were performed to compare GMV differences among the three groups, controlling for age, sex, education, and total intracranial volume. Post hoc analyses were conducted for significant clusters, and partial correlation analyses examined associations between abnormal GMV and symptom severity.

Significant group differences in GMV were found in the left middle frontal gyrus, left postcentral gyrus, left putamen, and right superior frontal gyrus. Both GAD and MDD patients showed decreased GMV in the left middle frontal gyrus and left postcentral gyrus, and increased GMV in the left putamen, compared with HCs. In contrast, decreased GMV in the right superior frontal gyrus was observed only in MDD patients and was positively correlated with both anxiety and depressive symptom severity.

These findings suggest that GAD and MDD share GMV alterations in prefrontal, somatosensory, and striatal regions, whereas reduced GMV in the right superior frontal gyrus was observed only in the MDD group.