The cholinergic anti-inflammatory reflex as a function of depression severity in adolescent non-suicidal self-injury

Objectives: Non-suicidal self-injury (NSSI) is associated with pro-inflammatory states. The cholinergic anti-inflammatory reflex is a neural pathway, modulating the body’s inflammatory response. This study aimed to investigate the cholinergic anti-inflammatory reflex in adolescents with and without NSSI in a first, cross-sectional observational study. Methods: Heart rate variability (HRV; a proxy for vagus nerve activity), inflammatory markers (leukocytes, c-reactive protein (CRP), interleukin-6 (IL-6)) and several clinical measures were assessed in female adolescents with NSSI (n = 154) and healthy controls (n = 46). Statistical analyses tested for group differences and correlations between HRV, inflammatory markers and depression in patients and controls. Mediation analyses were conducted to test direct and indirect effects. Results: The NSSI group showed greater depressive symptoms and leukocyte levels, but lower HRV compared to the control group. In the full sample, depression severity was positively correlated with leukocyte and CRP levels and negatively correlated with HRV. HRV was also negatively correlated with leukocyte and CRP levels. Depression severity mediated the association between leukocytes and HRV. Conclusions: Overall, this study lends initial support that lower vagal activity is associated with increased inflammatory markers in a sample of adolescents with NSSI which suggests altered functioning of the cholinergic anti-inflammatory reflex.