Prefrontal mechanisms of comorbidity from a transdiagnostic and ontogenic perspective

Accumulating behavioral and genetic research suggests that most forms of psychopathology share common genetic and neural vulnerabilities and are manifestations of a relatively few core underlying processes. These findings support the view that comorbidity mostly arises, not from true co-occurrence of distinct disorders, but from the behavioral expression of shared vulnerability processes across the life span. The purpose of this review is to examine the role of the prefrontal cortex (PFC) in the shared vulnerability mechanisms underlying the clinical phenomena of comorbidity from a transdiagnostic and ontogenic perspective. In adopting this perspective, we suggest complex transactions between neurobiologically rooted vulnerabilities inherent in PFC circuitry and environmental factors (e.g., parenting, peers, stress, and substance use) across development converge on three key PFC-mediated processes: executive functioning, emotion regulation, and reward processing. We propose that individual differences and impairments in these PFC-mediated functions provide intermediate mechanisms for transdiagnostic symptoms and underlie behavioral tendencies that evoke and interact with environmental risk factors to further potentiate vulnerability.