In Search of HPA Axis Dysregulation in Child and Adolescent Depression

Abstract

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.

Hypothalamic-pituitary-adrenal axis function during perinatal depression

“…These hormones play pivotal roles in metabolic, energetic, and growth-associated functions, blastocyst implantation, trophoblast invasion, and the placentation process, facilitating recognition of the fetal allograft during pregnancy. Moreover, these factors have been implicated in mood and/or depressive-like behaviors [5,10,11] .…”

“…The HPA axis, along with the sympathetic-adrenalmedullary axis, is one of the major biological stress response systems in humans [11] . Many of the hallmark symptoms of depression refl ect processes of hypothalamic dysfunction, such as disturbances of mood, appetite, sleep, sex-drive, and motivation.…”

“…Anxiety, depressive disorder, and stress during pregnancy are risk Phillipe Leff Gelman, et al HPA axis in perinatal depression 339 factors for negative outcomes in newborns, like preterm birth or low birth weight; also, insecure attachment and impaired child development could be a consequence of mental disorders during pregnancy [6,[8][9][10] . The mechanisms by which maternal depression impacts fetal and neonatal development are currently under investigation; there is some evidence that depressive symptoms impact the infant's hypothalamic-pituitary-adrenal (HPA) axis, enhancing the levels of catecholamines and cortisol in the newborn [6,10] .The HPA axis, along with the sympathetic-adrenalmedullary axis, is one of the major biological stress response systems in humans [11] . Many of the hallmark symptoms of depression refl ect processes of hypothalamic dysfunction, such as disturbances of mood, appetite, sleep, sex-drive, and motivation.…”

“…These hormones play pivotal roles in metabolic, energetic, and growth-associated functions, blastocyst implantation, trophoblast invasion, and the placentation process, facilitating recognition of the fetal allograft during pregnancy. Moreover, these factors have been implicated in mood and/or depressive-like behaviors [5,10,11] .The wide and varied activities displayed by such factors suggest that the endocrine placenta interacts with both the brain and the HPA system to produce homeostatic balance and optimal metabolic, energetic, and growth-related activity in order to bring a pregnancy to full term with a successful neonatal outcome (Fig. 1).…”

An empirical attempt at evaluating stress: A failure discovered through cross-validation

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