The relationship between plasma interleukin-6 and cognition based on curve correlation in drug-naïve patients with major depressive disorder

Background: The effect of interleukin-6 (IL-6) on cognition in patients with major depressive disorder (MDD) remains unclear. The aim of the present study was to investigate for the first time the non-linear relationship between plasma IL-6 and cognition and its sex-specific associations in patients with drug-na & iuml;ve MDD. Methods: A total of 326 participants, including 237 drug-na & iuml;ve MDD patients and 89 healthy controls (HCs), were included in this study. All participants completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and fasting venous blood was collected for IL-6 measurement. Patients with MDD completed the Hamilton Depression Scale-17 (HAMD-17) and the Hamilton Anxiety Scale-14 (HAMA-14) assessments. Two-way analysis of variance and curve estimation analyses were used to explore the effects of IL-6 on cognition and its sex differences. Results: We found that IL-6 and cognition were associated in different patterns in HCs and MDD patients. The best model for curve estimation between IL-6 and attention (F = 2.736, p = 0.045) and HAMA (F = 6.416, p < 0.001) in females with MDD was the cubic model. In male MDD patients, the best model for curve estimation between IL-6 and immediate memory was the cubic model (F = 3.077, p = 0.034). However, in HCs, the best model for curve estimation analysis between IL-6 and language was the quadratic model (F = 3.803, p = 0.026). Limitations: The main limitations were cross-sectional design. Conclusion: There was a non-linear and sex-specific relationship between IL-6 levels and cognition in patients with MDD.