Dr. Lee S. Cohen, Director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, recently shared his insights on mitigating psychiatric relapse during pregnancy amidst the COVID-19 pandemic with Ob.Gyn News on August 20th, 2021.

Postpartum depression, in many respects, has become a household term. Over the last decade, there has been increasing awareness of the importance of screening for postpartum depression, with increased systematic screening across clinical settings where care is delivered to women during pregnancy and the postpartum period. There have also been greater efforts to identify women who are suffering postpartum depression and to support them with appropriate clinical interventions, whether through psychotherapy and/or pharmacologic therapy. Clinical interventions are supplemented by the increasing awareness of the value of community-based support groups for women who are suffering from postpartum mood and anxiety disorders.Despite the growing, appropriate focus on recognition and acute treatment of postpartum depression as well as assessing clinical outcomes for those who suffer from postpartum mood and anxiety disorders, less attention has been given to postpartum psychosis, the most severe form of postpartum depression. It is indeed, the least common postpartum psychiatric syndrome (1 in 1,000 births) and comes to public attention when there has been a tragedy during the acute postpartum period such as maternal suicide or infanticide. In this sense, postpartum psychosis is ironically an underappreciated clinical entity across America given its severity, the effect it has on longer-term psychiatric morbidity, and its effect on children and families.

Our group at the Center for Women’s Mental Health has been interested in postpartum psychosis for years and started the Postpartum Psychosis Project in an effort to better understand the phenomenology, course, treatment, outcome, and genomic underpinnings of postpartum psychosis. Risk factors that are well established for postpartum psychosis have been described and overwhelmingly include patients with bipolar disorder. The risk for recurrent postpartum psychosis in women who have had a previous episode is as great as 75%-90% in the absence of prophylactic intervention. With that said, we are extremely interested in understanding the etiology of postpartum psychosis. Various studies over the last 5 years have looked at a whole host of psychosocial as well as neurobiologic variables that may contribute to risk for postpartum psychosis, including dysregulation of the stress axis, heightened inflammation as well as a history of child adversity and heightened experience of stress during the perinatal period.

There have also been anecdotal reports during Virtual Rounds at the Center for Women’s Mental Health of higher recent rates of postpartum psychosis manifesting during the postpartum period. This is a clinical observation and has not been systematically studied. However, one can wonder whether the experience of the pandemic has constituted a stressor for at-risk women, tipping the scales toward women becoming ill, or whether clinicians are seeing this finding more because of our ability to observe it more within the context of the pandemic.

Precise quantification of risk for postpartum psychosis is complicated; as noted, women with bipolar disorder have a predictably high risk for getting ill during the postpartum period and many go on to have clinical courses consistent with recurrent bipolar disorder. However, there are other women who have circumscribed episodes of psychotic illness in the postpartum period who recover and are totally well without any evidence of psychiatric disorder until they have another child, at which time the risk for recurrence of postpartum psychosis is very high. Interest in developing a model of risk that could reliably predict an illness as serious as postpartum psychosis is on the minds of researchers around the world.

One recent study that highlights the multiple factors involved in risk of postpartum psychosis involved a prospective longitudinal study of a group of women who were followed across the peripartum period from the third trimester until 4 weeks postpartum. In this group, 51 women were at increased risk for postpartum psychosis based on their diagnosis of bipolar disorder, schizoaffective disorder, or a previous episode of postpartum psychosis. These women were matched with a control group with no past or current diagnosis of psychiatric disorder or family history of postpartum psychosis. The findings suggested that women at risk for postpartum psychosis who experienced a psychiatric relapse during the first 4 weeks postpartum relative to women at risk who remained well had histories of severe childhood adversity as well as biomarkers consistent with a dysregulated stress axis (a statistically higher daily cortisol level). This is consistent with other data that have implicated the complex role between psychosocial variables as well as neurobiologic variables, such as a dysregulation in the hypothalamic pituitary adrenal axis and other studies that suggest that dysregulated inflammatory status may also drive risk for postpartum psychosis (Hazelgrove K et al. Psychoneuroendocrinology. 2021 Jun. doi: 10.1016/j.psyneuen.2021.105218).

At the end of the day, postpartum psychosis is a psychiatric and obstetrical emergency. In our center, it is rare for women not to be hospitalized with this condition to ensure the safety of the mother as well as her newborn, and to also get her recompensated and functioning as quickly and as significantly as possible. However, an interesting extrapolation of the findings noted by Hazelgrove and colleagues is that it raises the question of what effective treatments might be used to mitigate risk for those at greatest risk for postpartum psychosis. For example, are there other treatments over and above the few effective ones that have been studied as prophylactic pharmacologic interventions that might mitigate risk for recurrence of an illness as serious as postpartum psychosis?

The data suggesting dysregulation of the stress axis as a predictor variable for risk in women vulnerable to postpartum psychosis opens an array of opportunities that are nonpharmacologic, such as mindfulness-based cognitive therapy or other interventions that help to modulate the stress axis. This is a terrific opportunity to have pharmacologic intervention meet nonpharmacologic intervention to potentially mitigate risk for postpartum psychosis with its attendant serious sequelae.

In our own work, where we are evaluating genomic data in an extremely well-characterized group of women with known histories of postpartum psychosis, we are interested to see if we can enhance understanding of the model of risk for postpartum psychosis by factoring in genomic underpinning, history of diagnosis, and psychosocial variables to optimally craft interventions for this population of at-risk women. This brings us one step closer to the future in women’s mental health, to the practice of “precision reproductive psychiatry,” matching interventions to specific presentations across perinatal populations.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at obnews@mdedge.com.

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