In(s) and out(s) of adolescent depression - Trajectories of development and recovery.

While the role of biological markers in understanding major depressive disorder (MDD) in adults have been studied extensively, less has been done to identify the biomarkers of MDD development and recovery in adolescence. With the majority of mental health disorders starting in adolescence, identifying biomarkers of transition and recovery from MDD early in life is critical for developing effective prevention strategies. Considering most of the child and adolescent populations come from low-and-middle-income countries (LMICs), it is vital to focus on adolescent populations in these settings. With most studies coming from high-income countries (HICs), evidence suggests that elevated morning cortisol levels including cortisol awakening response (CAR), increased peripheral inflammation and brain abnormalities such as cortico-limbic dysregulation or blunted activity in reward related regions in response to positive information are associated with MDD and being at-risk for MDD development in adolescence. We also find that some of the biological mechanisms of recovery from MDD, mainly normalisation in the cortico-limbic dysregulation, are reported following psychological therapy, suggesting shared pathways leading to MDD vulnerability and recovery. Although, only a few studies include adolescent populations. Understanding molecular mechanisms through which psychological interventions are effective, as well as molecular markers of transition to depression in individuals at-risk, are important to inform effective prevention and intervention strategies.