Combined serum IL-6, C-reactive protein, and cortisol may distinguish patients with anhedonia in major depressive disorder.

Neuroinflammation and anhedonia in major depressive disorder (MDD) are closely connected, though the exact mechanism is unclear. This study aimed to investigate the relationships between cytokines, C-reactive protein (CRP), cortisol, and anhedonia, revealing the potential predictive value in identifying anhedonic MDD. In total, 66 patients with MDD (29 with anhedonia and 37 without anhedonia) and 66 healthy controls (HCs) were included. The severity of depression and anhedonia was evaluated using the Hamilton Rating Scale for Depression-24 (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS), respectively. Serum cytokines were measured using flow cytofluorometric kits, while CRP and cortisol were measured using enzyme-linked immunosorbent assay kits. We found higher serum levels of interleukin-2 (IL-2), IL-6, and cortisol in MDD than in HC where anhedonic MDD was highest. CRP and IL-6 were positively associated with anhedonia, and cortisol levels were related to both anhedonia and depression. A combination of IL-6, CRP, and cortisol had optimal predictive value for distinguishing anhedonic MDD. Anhedonic MDD has unique neuroendocrine-immune characteristics compared with those without anhedonia. The combination of IL-6, CRP, and cortisol might be an early marker to distinguish anhedonic MDD.