Objective: Self-harm is associated with alterations in the psychobiological stress response. Specifically, the reactivity of the autonomic nervous system (ANS) and the endocrine hypothalamic-pituitary-adrenal (HPA) axis may differ in individuals who engage in self-harm. However, evidence in this regard is inconsistent.

Background: We conducted a preregistered random-effects meta-analysis of sympathetic ANS, parasympathetic ANS, sympathetic-parasympathetic, i.e., mixed-influence ANS, and HPA axis reactivity following laboratory stress exposure in individuals who engage in self-harm and controls. Stress exposure consisted of paradigms using either social-evaluative (e.g., TSST), emotional (e.g., negatively valenced visual stimuli), or physical (e.g., cold pressor test) challenges. A total of 29 studies (self-harm: n = 954, controls: n = 1122, 74% females) were included in the analysis.

Results: Regarding ANS reactivity to stress, no differences emerged between the two groups. However, parasympathetic ANS activity was lower before stress (g = -0.30, CI -0.51 to -0.09) and after stressor cessation (g = 0.54, CI -1.07 to -0.01) in the self-harm group compared to controls. Regarding HPA axis reactivity, individuals who engage in self-harm showed significantly lower cortisol responses to stress than did controls (g = -0.26, CI -0.45 to -0.08). After stressor cessation (i.e., during stress recovery), cortisol was also lower in individuals who engage in self-harm compared to controls (g = -0.26, CI -0.43 to -0.08).

Conclusions: Lower basal parasympathetic ANS activity and flattened cortisol responses indicate dysregulation of psychobiological stress systems in individuals who engage in self-harm. A better understanding of the psychobiological underpinnings of self-harm may allow for the establishment of biomarkers of risk stratification and treatment monitoring in affected individuals.