The Cholinergic Anti-Inflammatory Reflex as a Function of Depression Severity in Adolescent Non-Suicidal Self-Injury

A growing body of research has demonstrated a link between non-suicidal self-injury (NSSI) and mood disorders with pro-inflammatory states. The cholinergic anti-inflammatory reflex is a neural pathway that helps modulate the body’s inflammatory response and has been posited as a potential avenue for adjuvant treatment in mental disorders. However, no study to date has investigated the functioning of the cholinergic anti-inflammatory reflex in a clinical adolescent population with NSSI. This study measured 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 in female adolescents with NSSI (n = 154) along with healthy controls (n = 46). Statistical analyses tested for group differences and correlations between HRV, inflammatory markers and depression in the NSSI group. Mediation analyses were conducted to test direct and indirect effects. 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. Overall, this study supports the notion 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.