The HPA axis and perinatal depression: a hypothesis

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.