Peripheral pro-inflammatory cytokine levels are associated with brain structural atrophies in patients with anxious...

Anxious depression (AD), a common neurophysiological subtype of major depressive disorder (MDD), is often accompanied by immune dysregulation and volumetric alterations in brain structures. However, the intrinsic relationships between inflammatory markers and brain structural changes in AD patients remain unclear.

Participants were categorized into three groups: the AD group (n = 43), the non-anxious depression group (NAD, n = 68), and healthy controls (HC, n = 53), matched for age, sex, and education level. Serum levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were measured across the groups. All participants underwent T1-weighted magnetic resonance imaging (MRI) scans, and voxel-based morphometry (VBM) analysis was performed to assess gray matter volume (GMV). Correlation analyses were conducted to investigate potential associations between inflammatory markers and GMV in the AD group.

Compared to HCs, patients with MDD exhibited significantly elevated serum IL-6 levels. Additionally, AD patients demonstrated reduced GMV in the right putamen, right superior temporal gyrus (STG), and right cuneus compared to both NAD and HC groups. Notably, reduced GMV in the right STG was significantly correlated with serum IL-1β levels and depression severity within the AD group.

These findings provide preliminary psychoradiological evidence for the pathophysiological mechanisms underlying this MDD subtype and possible explanations for the differences in clinical features and prognosis between AD and NAD.