Postpartum Depression and the dysregulated HPA axis: biological hypothesis

Shilpi Awasthi


Postpartum depression (PPD) is a clinical condition that has a severe impact on mood and lasts for more than 10 days after delivery. Symptoms include feelings of worthlessness, shame, lack of motivation and thoughts of hurting oneself or the baby. It is diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). In comparison to postpartum blues, PPD lasts longer and has a more severe impact on the mother. Worldwide, PPD affects up to 15% of mothers and  87% of these women do not seek or attain support. Barriers to this may be due to a lack of education and social stigma.

Some of the pathological theories for PPD correlate to those explaining psychiatric illnesses. This may not be justified as there are many biological and social events that occur exclusively to women during pregnancy and postpartum. Given the lack of current biological understanding, this article aims to explore the hypothesis of Hypothalamic-pituitary-adrenal (HPA) axis dysregulation in PPD.

PPD not only affects the mother’s health but can also cause serious developmental problems to the child. For example, a study found that children of depressed mothers were about three times more likely to experience depression by age 16 than children of non-depressed mothers. This supports that it is imperative to have a better biological understanding of PPD to identify mothers at risk, and potentially allow for better therapies in the future.

Stress is one of the major factors for the onset and prolongation of depressive symptoms. Cortisol is released in response to this - allowing it to be used as a key marker for the stress response. Consequently, there have been propositions that PPD may be associated with abnormal cortisol levels, two of which have been explored below:

First hypothesis:  Hypercortisolaemia can increase the risks of developing depressive symptoms especially in the presence of environmental stressors. 

As the placenta develops it produces cortisol releasing hormone (CRH) in addition to the maternal CRH. Both forms of CRH are similar in terms of biological activity. However, the placental CRH is stimulated (not negatively regulated) by maternal cortisol, leading to an exponential increase in cortisol of up to 60 to 700 times during pregnancy. 


In the postpartum period, there will be reduced activation in the PVN (paraventricular nucleus) due to negative feedback from the high cortisol levels. PVN is found in the hypothalamus and is important for responding to external stressors - this would now be reduced. Also since cortisol plays a role in limbic processing, there may be an alteration in this - affecting the response to emotional stressors.


Second hypothesis: Overadjustment of HPA feedback  causing PPD


After pregnancy there is expected to be a major decline in cortisol levels, this is self-adjusted generally in women during postpartum, where the cortisol goes back to the normal pre-pregnant level as the HPA axis is attenuated. However in PPD, this doesn’t occur and there is an over adjustment in the HPA feedback sensitivity, where the decline of cortisol sequentially decreases CRH and ACTH. A decrease in ACTH, in turn, decreases cortisol, resulting in hypocortisolaemia meaning there is not enough for the dopaminergic system - thereby triggering depressive emotions, and to fulfill the body’s needs in general. 


Mechanisms such as those explained above are just a starting point towards a more scientific underpinning for PPD – which is crucial to understand, given the serious implications on both mother and infant.  Future medical research enabling better scientific understanding of PPD could allow better identification of mothers at risk - enabling preventative actions and for more effective biological therapies for PPD. 


References:

  1. https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-016-0915-y

  2. https://www.karger.com/Article/FullText/354702

  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918890/

Comments

  1. Bipin23 July 2020 at 07:15

    Very interesting and educating article.

    ReplyDelete
    Replies
    1. Universal Medicine Team14 August 2020 at 20:47

      Glad you found this article informative and we hope that you continue to follow our posts!

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