Linking peripheral IL-6, IL-1β and hypocretin-1 with cognitive impairment from major depression

Background: Cognitive impairment has long challenged the patients with major depressive disorder (MDD), hypocretins and inflammation have recently been implicated in cognitive function. However, limited studies have compressively assessed their associations with cognitive impairment in MDD. Methods: A total of 100 MDD patients and 100 healthy controls (HC) were recruited for this study. They were tested with HAMD, HAMA, and MCCB scales. The plasma level of selected inflammatory factors (IL-1 beta, IL-6, and TNF-alpha) and hypocretin-1 were determined using enzyme-linked immunosorbent assay (ELISA). Correlation analysis was performed to explore the relationship between the plasma level of the factors and clinical performances. Results: Patients with MDD showed cognitive impairment in each MCCB subdomain except working memory compared with HC. The levels of IL-6, IL-1 beta and hypocretin-1 in MDD patients were higher than HC. Besides, IL-1 beta levels was negatively correlated with overall cognitive function in the combined group. Hypocretin-1 was positively correlated with socially cognitive impairment in MDD patients. A negative correlation between plasma hypocretin-1 levels and HAMA scales was also observed in MDD patients. Limitation: The study was cross-sectional, thereby limiting causal inference, and had a relatively small sample size. There are no subcategories for MDD based on characteristics. Conclusion: IL-1 beta, IL-6 and Hypocretin-1 were reported as potential factors involved in MDD pathology. Hypocretin-1 could contribute to the biological mechanisms of anxiety relief. Hypocretin-1, therefore, may be important in exploring the pathological mechanisms of social cognitive impairment in MDD patients. Conclusively, this study provides new insights for exploring cognitive impairment in depression.