The HPA axis and perinatal depression: a hypothesis

Abstract

Episodes of depression and anxiety are as common during pregnancy as postpartum. Some start in pregnancy and resolve postpartum, others are triggered by parturition and some are maintained throughout. In order to determine any biological basis it is important to delineate these different subtypes. During pregnancy, as well as the rise in plasma oestrogen and progesterone there is a very large increase in plasma corticotropin releasing hormone (CRH), and an increase in cortisol. The latter reaches levels found in Cushing's syndrome and major melancholic depression. Levels of all these hormones drop rapidly on parturition.We here suggest that the symptoms of antenatal and postnatal depression may be different, and linked in part with differences in the function of the hypothalamic pituitary adrenal (HPA) axis. There are two subtypes of major depression, melancholic and atypical, with some differences in symptom profile, and these subtypes are associated with opposite changes in the HPA axis. Antenatal depression may be more melancholic and associated with the raised cortisol of pregnancy, whereas postnatal depression may be more atypical, triggered by cortisol withdrawal and associated with reduced cortisol levels. There is evidence that after delivery some women experience mild bipolar II depression, and others experience post traumatic stress disorder. Both of these are associated with atypical depression. It may also be that some women are genetically predisposed to depression of the melancholic type and some to depression of the atypical type. These women may be more or less vulnerable to depression at the different stages of the perinatal period.

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] .…”

“…In addition, women with different genetic predispositions (e.g., glucocorticoid (GC) receptor polymorphisms) are reported to be at risk of becoming ill with a depressive episode at various times in the perinatal period [10] . [5,6,27,28] .…”

“…Meta-analysis studies have reported that the mean prevalence rate of prenatal depression is ~12% (this varies greatly according to location, mode of assessment, and socioeconomic conditions), and show that a large percentage of pregnant women displaying major depression remain depressed in the postpartum period and/or continuously [6,7] . 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] .…”

“…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).…”