Cytokines and cognitive function in first-episode drug-naïve MDD: an inflammation panel perspective

Inflammation is involved in the process of cognitive impairment in some psychiatric disorders; however, the relationship between cognitive function and inflammation markers in major depressive disorder (MDD) remains unclear. Herein, we sought to investigate the alterations in cytokine levels and the relationships between cytokine levels and cognitive performance in MDD patients and healthy controls (HCs) from the perspective of the inflammation panel. This present study included 170 participants, including 101 first-episode drug-naïve MDD patients and 69 HCs. The levels of 27 cytokines were assayed by the Bio-Plex human 27-plex (BioRad). The depressive and anxiety symptoms were evaluated using the Hamilton Depression Rating Scale-17 (HAMD-17) and Hamilton Anxiety Rating Scale-14 (HAMA-14), respectively. The cognitive function was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Toronto Alexithymia Scale (TAS-20). First-episode drug-naïve MDD patients exhibited significantly poorer neurocognitive and social cognitive function compared to HCs, even after adjusting for potential confounders. Of the 27 cytokines measured, 26 were significantly elevated in MDD patients. The principal component analysis identified five components accounting for 71.26% of the variance, with four components differing significantly between the MDD and HC groups. Notably, PC3, comprising RANTES, IL-9, MIP-1beta, TNF-alpha, IL-2, and IL-10, demonstrated strong discriminative power between MDD and HCs (AUC = 0.829, 95%CI: 0.769-0.889). The analysis revealed that PC3 and its contained cytokines (RANTES, IL-9, IL-2, and IL-10) exhibited a negative correlation with the scores of TAS-20, RBANS, and its subscales in HCs, but no such associations were observed in MDD patients. Our findings may contribute to elucidating the biological mechanisms underlying cognitive impairment in MDD by emphasizing the relationship between cytokine subtypes, including RANTES, IL-9, IL-2, and IL-10, and cognitive functions.