Dispositional forgiveness is positively associated with many facets of wellbeing and has protective implications against depression and anxiety in adolescents. However, little work has been done to examine neurobiological aspects of forgiveness as they relate to clinical symptoms. In order to better understand the neural mechanisms supporting the protective role of forgiveness in adolescents, the current study examined the middle frontal gyrus, which comprises the majority of the dorsolateral prefrontal cortex and is associated with cognitive regulation, and its relationship to (...) forgiveness and clinical symptoms in a sample of healthy adolescents. In this cross-sectional study, larger MFG volume was significantly associated with higher self-reported dispositional forgiveness scores and lower levels of depressive and anxiety symptoms. Forgiveness mediated the relationship between MFG volume and both depressive and anxiety symptom levels. The mediating role of forgiveness in the relationship between MFG volume and clinical symptoms suggests that one way that cognitive regulation strategies supported by this brain region may improve adolescent mental health is via increasing a capacity for forgiveness. The present study highlights the relevance of forgiveness to neurobiology and their relevance to emotional health in adolescents. Future longitudinal studies should focus on the predictive quality of the relationship between forgiveness, brain volume and clinical symptoms and the effects of forgiveness interventions on these relationships. (shrink)