In Search of HPA Axis Dysregulation in Child and Adolescent Depression

Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis in adults with major depressive disorder is among the most
consistent and robust biological findings in psychiatry. Given the importance of the adolescent transition to the development
and recurrence of depressive phenomena over the lifespan, it is important to have an integrative perspective on research investigating
the various components of HPA axis functioning among depressed young people. The present narrative review synthesizes evidence
from the following five categories of studies conducted with children and adolescents: (1) those examining the HPA system’s
response to the dexamethasone suppression test (DST); (2) those assessing basal HPA axis functioning; (3) those administering
corticotropin-releasing hormone (CRH) challenge; (4) those incorporating psychological probes of the HPA axis; and (5) those
examining HPA axis functioning in children of depressed mothers. Evidence is generally consistent with models of developmental
psychopathology that hypothesize that atypical HPA axis functioning precedes the emergence of clinical levels of depression
and that the HPA axis becomes increasingly dysregulated from child to adult manifestations of depression. Multidisciplinary
approaches and longitudinal research designs that extend across development are needed to more clearly and usefully elucidate
the role of the HPA axis in depression.