Hypothalamic-pituitary-adrenal axis dysregulation in depressed adolescents with non-suicidal self-injury. Psychoneuroendocrinology Non-suicidal self-injury (NSSI) is characterized by causing harm to one's own body without the intent of suicide. While major depressive disorder (MDD) has been associated with elevated cortisol (at least in some subgroups), prior studies in NSSI have suggested that NSSI is associated with blunted reactivity to stress of the hypothalamic-pituitary-adrenal (HPA) axis, possibly consistent with an allostatic load model. The present study used a multi-level approach to examine salivary cortisol in the context of a social stressor in 162 adolescents (ages 12 to 19 years old) with MDD with a history of repeated engagement in NSSI (MDD/NSSI) versus MDD without repeated NSSI (MDD), and healthy controls (HC). Observed (expressed) and self-reported (experienced) ratings of stress were also obtained during the social stress paradigm. The results showed that MDD/NSSI exhibited lower salivary cortisol levels and differed in cortisol trajectories in the context of a social stressor compared to HC and MDD. Observed stress, but not self-reported stress, during the social stress paradigm was greater for the MDD/NSSI than HC. Follow-up analyses suggested the possibility that this pattern of lower cortisol for those who engage in NSSI was present in females and males, and was more pronounced in those with repeated NSSI (but not subthreshold NSSI) and those with a history of NSSI and suicide attempts. Overall, these findings add to the prior literature and begin to show a consistent pattern for how stress is processed in atypical ways for those who engage in repeated NSSI. Importantly, these results suggest that some of the heterogeneity across adolescent depression may be better represented by these underlying biological processes, perhaps even representing subgroups that will benefit from different types of intervention. Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Adolescents with Non-Suicidal Self-Injury. 10.1016/j.psyneuen.2018.11.004