This study investigates structural abnormalities in hippocampal subfield volumes and shapes, and their association with plasma CC chemokines in individuals with major depressive disorder (MDD).

A total of 61 patients with MDD and 65 healthy controls (HC) were recruited. All participants underwent high-resolution T1-weighted imaging and provided blood samples for the detection of CC chemokines (CCL2, CCL7, and CCL11). Comparisons of hippocampal subregion volumes, surface shapes, and plasma CC chemokine concentrations were conducted between the MDD and HC groups. Furthermore, partial correlation analysis was performed to assess the relationship between structural abnormalities (hippocampal subfield volume and shape) and plasma CC chemokine levels.

The MDD group exhibited a significant reduction in the volume of the left hippocampal tail compared to the HC group (F = 9.750, Bonferroni-corrected p = 0.026). No significant outward or inward deformation of the hippocampus was detected in MDD patients relative to the HC group (all FWE-corrected p > 0.05). Additionally, plasma CCL11 levels were elevated in the MDD group compared to the HC group (F = 9.982, p = 0.002), with these levels showing a positive correlation with the duration of the illness (r = 0.279, p = 0.029). Partial correlation analysis further revealed a negative correlation between the smaller left hippocampal tail volume and plasma CCL11 levels in MDD patients (r = −0.416, p = 0.001).

Abnormally elevated plasma CCL11 in MDD patients may mediate damage to specific hippocampal substructures.