50 In depressed patients, it has been shown that there is a change in the regulation of the HPA axis.51 A hallmark feature that characterizes the HPA axis in depression is the altered response to stress and inability to maintain regulation: indeed, hyperactivity of the HPA axis is one of the most robust biological findings Inhibitors,research,lifescience,medical in major depression.51 Both women with PPD and women with nonpuerperal MDD show abnormalities in HPA axis activity. In general women (and men) suffering from MDD exhibit high cell assay baseline cortisol and an exaggerated response to the dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test. However, in the first few weeks

postpartum, euthymic women demonstrate an HPA axis that remains refractory to external CRH challenge.

In contrast, women with PPD have been shown to experience an ongoing blunting of ACTH response to corticotrophin-releasing hormone (CRH) at 6 to 12 Inhibitors,research,lifescience,medical weeks postpartum compared with nondepressed women, interpreted as reflecting an ongoing hyporeactive HPA axis.43 Additionally, Bloch et al observed that currently euthymic women with a past history of PPD experienced an increased cortisol response and onset of significant depressive symptoms when exposed to Inhibitors,research,lifescience,medical a protocol consisting of high-dose gonadal steroid administration followed by abrupt withdrawal. This observed effect in those women with a history of PPD was in marked contrast to the group of women without a history of PPD who experienced no observed mood disturbance Inhibitors,research,lifescience,medical when exposed to the same protocol. Thus, this work suggests either a trait vulnerability related to the onset of PPD or a consequence of an earlier depression.45 Interestingly, the HPA axis has also been a focus of recent efforts to identify a biomarker for those at risk for perinatal or postpartum depression.

In particular, elevated placental CRH has been a potential candidate with Inhibitors,research,lifescience,medical earlier literature demonstrating conflicting etc results.52,53 The increasing production of placental CRH (pCRH) throughout pregnancy can be measured in maternal peripheral blood54 and within hours after childbirth, levels of pCRH quickly drop and become undetectable.55 Nonetheless, the role of midpregnancy pCRH as a biomarker of maternal prenatal and PPD does not appear to be clinically useful, and the most recent Batimastat report did not demonstrate an association between increased midpregnancy pCRH and increased risk for either depression during pregnancy nor PPD.56 Moreover, while the dysregulated HPA axis in PPD is interesting, disturbances in other endocrine systems may also play a role in the etiology of PPD. For example, one study has demonstrated that women with antenatal total and free thyroxine concentrations in the lower euthyroid range may be at greater risk of developing postpartum depressive symptoms.