Pregnancy and Mental Health: New Research Paves the Way for Better Treatment

Authors: Wansu Qiu (Ph.D. candidate), Liisa A.M. Galea (PhD, Graduate Program in Neuroscience, Department of Psychology. Djavad Mowafaghian Centre for Brain Health, University of British Columbia) & Katherine Moore (Adv. Dip., BA)

Pregnancy and postpartum are two periods in a person’s lifetime that cause major changes to the body and brain. Anyone who has been pregnant will no doubt be fully aware of the dramatic changes to their bodies. But what is perhaps less well known is that there are also changes that occur in the brain. Indeed, you may be familiar with the term “baby brain” or “maternal amnesia”. These terms are often used in a derogatory way towards new parents, but people need to be aware that changes to the brain do occur and can have a significant impact on mental health.

Unfortunately, many of the natural brain changes that occur during pregnancy and the postpartum period are similar to what we see in people with major depression. These changes include, but are not limited to, reductions in brain volume, increased inflammation, hormonal profile changes, and metabolism changes. So, it is natural to wonder whether and how these natural changes contribute to greater susceptibility to depression during pregnancy or postpartum.

It turns out that the perinatal period (pregnancy and postpartum) is a particular time of risk to develop depression. Perinatal depression is defined as depression that occurs during pregnancy or in the first few months following childbirth and affects approximately 15% of new parents. However, not all people that experience perinatal depression develop symptoms at the same time or have the same symptoms. For example, the majority of people with perinatal depression experienced depression at least once before their pregnancy. However, 40% of people with perinatal depression experienced depression for the first time in their lives in the early postpartum period. Unfortunately, research has typically not separated findings according to when depression starts. This is problematic because knowing when depressive symptoms begin can help us determine the cause of depression (etiology), as well as how to properly treat it. In fact, studies that separate findings by depression onset (e.g. during pregnancy versus postpartum) and include whether there was a previous history of depression, show that the success of antidepressants vary depending on these factors. Thus, the distinct biological changes between pregnancy and postpartum may be the reason why drug effectiveness changes during these periods.

Yet, very little research exists on the connection between these biological mechanisms, depression that starts during the perinatal period and treatment efficacy. Our lack of understanding is partially due to the misidentification of perinatal depression as just another form of major depression. This issue stems from the fact that current diagnostic manuals, such as the DSM-V, do not distinguish between depression onset during pregnancy versus depression onset during postpartum. Furthermore, they only consider depression occurring in the first four weeks after birth as the postpartum period, when in fact many distinct physiological changes occur well into the first year of motherhood that may impact depression susceptibility. Considering the large number of people that live with postpartum depression, but who have never experienced depression before, it is pertinent to determine why this period has such a high risk for depression onset. Even more troubling, antidepressant treatments may be less effective when treating perinatal depression compared to treating depression at other times. Indeed, the effectiveness of antidepressants is even worse in the postpartum period compared to other periods of pregnancy such as preconception.

Sadly, pregnant and postpartum people are not often studied and are left out of clinical trials. The lack of females in research is troubling enough given the greater number of pharmaceutical side effects they experience and misdiagnosis they receive compared to men. This is compounded by the lack of data on the safety and efficacy of drugs during the perinatal period. Interestingly, there has been a surge in preclinical animal models of perinatal depression over the last 20 years. These studies have also shown that antidepressants are less effective when depression onset is during the postpartum. Specifically, using a preclinical model of first-time postpartum depression onset, researchers found that high-stress hormone levels cause depressive-like symptoms including passive coping, reduced maternal care (e.g. more time spent away from the nest) and decreased plasticity in the hippocampus. Interestingly, the hippocampus is an area of the brain that is affected by depression in human populations too. In a series of studies, researchers also found that a common antidepressant, fluoxetine (Prozac), shows limited effectiveness in treating these symptoms in the postpartum. This mirrors previous findings in humans on antidepressant use during postpartum. Astonishingly, they found that fluoxetine reversed the decrease in maternal care behaviour in the early postpartum but did not reverse depressive symptoms (e.g. brain changes, passive coping) in the later postpartum, suggesting that fluoxetine may lose its effectiveness over time.

In a recent article, cluster member (Wansu Qiu: @WQiuPhoenix) wanted to understand what mechanisms or biomarkers may be limiting the efficacy of fluoxetine in the postpartum. Using this same preclinical model, Qiu and colleagues discovered that inflammation and metabolism may play a role in the lack of antidepressant efficacy during postpartum in females. Inflammation is important to examine because depression has been linked to increased inflammatory signalling and antidepressant effectiveness has been linked to decreased inflammatory signalling. Fluoxetine treatment in the postpartum increased a proinflammatory signal, IL-1β (a cytokine), in the hippocampus and decreased tryptophan concentrations. This is notable as fluoxetine usually decreases cytokines when it reverses symptoms, and decreased tryptophan is often found in depression in females. More alarmingly, they found that the effects of fluoxetine were still present when rat moms were given a high dose. Thus, the authors suggest that the lack of treatment efficacy is not due to how antidepressants are metabolized in the maternal body, but due to changes in drug action on inflammation and metabolism. Overall, these new findings suggest that the lack of effectiveness of fluoxetine to reverse symptoms in the postpartum may be related to tryptophan metabolism, possibly acting via inflammation in rodent moms. This new research can lead to a better understanding of postpartum depression and antidepressant efficacy, possibly paving new ways for better treatment options.

The bottom line: scientists need more research funding to study the distinct presentations of perinatal depression (pregnancy onset versus postpartum onset) and we need more researchers to take on these kinds of projects. Clinicians need to be on the lookout for perinatal mood disorders, and we need governments to develop a national strategy for perinatal mental health. As a society, we all need to support people not just during pregnancy but also in the postpartum-as they say, it takes a village.

Originally published at https://womenshealthresearch.ubc.ca July 7, 2021

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