Recent advances in understanding maternal perinatal mood disorders

Introduction

The most recent advances in the study of perinatal mental health fall into several categories. We have first addressed updates to our understanding of the epidemiological patterns and clinical manifestations of perinatal mood disruption. Next, we have discussed updates to expert guidelines for screening. We cover critical recent additions to the ongoing conversation about treatment efficacy and about the relative contributions of maternal mental illness versus psychotropic medications to obstetric, neonatal, and childhood outcomes.

Part I: Advances in understanding epidemiology, phenomenology, and pathophysiology of perinatal mood disruption

Scholarship in recent years has added important insights to our understanding of the landscape of perinatal mental health. Past work had revealed major roles for mood disorder history (particularly a history of the diagnosis of bipolar disorder, or BD), poor social supports, and a history of maltreatment^1,2. Recent research has provided new information about the role of bipolar diathesis, personality factors, anxiety disorders, and obstetrical complications in the risk for postpartum depression.

Although it has been known for some time that BD confers a greatly increased risk of mood disruption in the perinatal period^3,4, evidence recently has accumulated that many women initially diagnosed with unipolar postpartum depression in fact suffer from “hidden” BD. Sharma et al.⁵ published the results of a prospective study of 142 postpartum women, demonstrating a rate of diagnostic conversion (from unipolar to bipolar) in the postpartum period of 6.52%, which is 11- to 18-fold higher than diagnostic conversion rates measured in other populations. This study also used validated diagnostic interviews with family members to identify family history of BD and found that conversion from unipolar to bipolar in the first six months postpartum was significantly associated with a family history of BD. This first prospective study of “switch rates” in perinatal mood disorders is extremely important as it guides the clinician to pay special attention to family history of BD and highlights the need to monitor postpartum patients carefully to rule out subtle signs of emerging hypomania and mixed symptoms. It also provides an understanding of the role of BD in treatment resistance in postpartum depression, as Sharma et al.⁶ have previously reported high rates of missed BD in patients referred for treatment-resistant postpartum depression. This recent recognition of high rates of bipolar II disorder in patients diagnosed with postpartum depression is further supported by a study by Mandelli et al.⁷ of women with major depression, bipolar I and II which found that 50% of the women with bipolar II had a history of postpartum depression compared with 27.5% of women with bipolar I and 21.6% of women with major depressive disorder.

Furthermore, in a prospective study by Wisner et al.⁸, 10,000 women were screened with the Edinburgh Postnatal Depression Scale (EPDS) between 4 and 6 weeks postpartum, patients were interviewed by using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders IV (SCID), and high rates of BDs (22.6%) were found in women who “screened positive” for postpartum depression (EPDS >10). Notably, high rates of anxiety disorders were also found, as nearly two thirds of patients had comorbid anxiety disorders. Anxiety during pregnancy is now recognized as an important risk factor for postpartum depressive symptoms⁹ as well as a risk factor for longer time to treatment response in postpartum depression¹⁰.

Recognition of the importance of maternal personality factors, particularly insecure attachment style, has also been growing. Robakis et al. (2016) (n = 107)¹¹ and Ikeda et al. (2016)¹² (n = 76) both published the results of prospective studies indicating a major role for antenatally measured attachment insecurity in the risk for postpartum depression. Robakis et al. used a longitudinal follow-up design that revealed the importance of maternal attachment style to be specific to the early postpartum period, whereas more classically recognized risk factors such as mood disorder history were of greater importance in predicting depression after the third postpartum month. Personality disorders existing prior to conception were demonstrated to be related to anxious and depressive symptoms in pregnancy, independently of the effect of coexisting mood or anxiety disorders¹³. Neuroticism, which has been previously identified as a risk factor, was also affirmed to confer significant risk for postpartum depression in a prospective study of 1,037 non-depressed pregnant women¹⁴.

Efforts to identify pathophysiological cascades and associated biomarkers for perinatal mood disorders are ongoing¹⁵; however, results have been heterogeneous to date and clear agreements have for the most part not emerged. However, low serum vitamin D stands out as a risk factor that has emerged across several recent studies^16–19, suggesting that screening and supplementation for vitamin D deficiencies could be clinically important.

Part II: Advances in screening for perinatal mood disorders

Recently, the considerable controversy regarding whether to recommend universal screening of all women for perinatal mood disorders has moved to a general consensus that this screening is worth the time and effort. The American College of Obstetricians and Gynecologists²⁰ and the American Academy of Pediatrics²¹ published position statements recommending screening of all women for depression during pregnancy and postpartum. Most recently, the US Preventive Services Task Force updated guidelines for screening for depression in adults to include screening for perinatal depression²². According to these recent guidelines, minimum screening for perinatal women includes screening for depression once during pregnancy and postpartum; however, since depression may evolve over the first postpartum year, it is recommended that clinicians consider continued screening, especially in high-risk groups. The recent findings of high rates of anxiety disorders in women who screen positive on the EPDS have increased the need for universal EPDS screening even further, since the EPDS has three questions (questions 3, 4, and 5) that can be used to identify anxiety symptoms, but further validation of the EPDS for screening of anxiety disorders is needed²³.

Part III: Obstetrical, fetal, and developmental outcomes: maternal mental illness versus pharmacological exposures

It is difficult to distinguish those adverse effects on obstetrical, fetal, and developmental outcomes attributable to psychotropic medication from the adverse effects attributable to maternal mental illness. The infeasibility of conducting randomized trials in pregnant women makes studies in this field difficult to control and their results difficult to interpret. In earlier years, there was perhaps a bias on the part of researchers toward assuming that adverse outcomes were related to medication. However, several recent studies using careful designs targeted to disentangle the contributions of medication from those of maternal illness have further revealed the true scope of the effects of perinatal mental illness.

The emerging consensus from the existing literature is that although antenatal administration of serotonin reuptake inhibitor (SRI) antidepressants does carry risks, most notably reduced term of gestation, pulmonary hypertension of the newborn, and neonatal withdrawal, these risks are manageable and accrue largely to SSRI use in the third trimester²⁴. More importantly, they pale in comparison to the effects of maternal mental illness, which are still being articulated fully but include poorer fetal outcomes²⁵, long-term effects on child behavior²⁶ and cognition²⁷, and maternal self-harm, the last of which recently was again shown to be the most common cause of death in a population of perinatal women²⁸. Less information is available on perinatal use of other classes of psychotropics, including mood stabilizers and antipsychotics. Recent advances in these areas are summarized below.

Part IV: Recent advances in acute pharmacologic and psychotherapy treatment of perinatal mood disorders

A meta-analysis of 40 randomized studies of cognitive behavior therapy (CBT) during pregnancy and the first year postpartum reported that CBT was associated with significant reduction in depressive symptoms⁵¹. Recent advances in CBT delivery have included internet-based CBT for postpartum depression, and this method was associated with improvement in depressive symptoms in preliminary investigations⁵². Interpersonal psychotherapy (IPT) remains an effective evidence-based treatment for postpartum depression⁵³, and recent adaptations have included a pilot study of partner-assisted IPT⁵⁴ and mother-infant IPT⁵⁵, both of which appear promising.

Although several systematic reviews have been completed that report that antidepressants are associated with significant reductions in depressive symptoms in women with unipolar depression postpartum^56,57, there is only one published study to date of the acute treatment of acute bipolar postpartum depression⁵⁸. In a chart review of 18 bipolar women who were treated with quietapine alone (or with sedative hypnotic), Sharma et al.⁵⁸ reported that 83% were much improved or improved on retrospective Clinical Global Impression Scale scores. Given that recent investigations have demonstrated high rates of postpartum depression in patients with BD, future psychopharmacologic and psychotherapeutic treatment studies are needed in this population.

Part V: Advances in preventing perinatal mood disorders

Although there have been many advancements in the study of risk factors for perinatal depression, advancement in methods to prevent perinatal depression has remained less studied, except in high-risk groups, such as women with BD. Recent studies have built upon the initial reports of Viguera et al.⁴ of high rates of relapse in bipolar pregnant women who discontinue lithium during pregnancy. For instance, Rosso et al.⁵⁹ reported in a study of 17 women with lithium-responsive bipolar I that continued use of lithium in pregnancy and postpartum resulted in reduced rates of postpartum relapse compared with previously published unmedicated relapse rates of 66%⁶⁰ to 75%⁶¹ in this population. Uguz et al.⁶² reported the first small case series of relapse risk in women who switched from other mood stabilizers such as lithium or valproic acid prior to pregnancy to olanzapine or quietapine in pregnancy. In their sample of eight women, none experienced relapse. Sharma and Sommerdyk⁶³, in their report of prevention of postpartum depression in three women with bipolar II disorder with the use of lamotrigine, also highlight the need for larger randomized trials of mood stabilizer treatments for management of BD in pregnancy and postpartum. Lithium prophylaxis immediately postpartum has been shown to decrease relapse in those very-high-risk women with histories of postpartum mania and psychosis⁶⁴.

Summary and conclusions

The most recent updates in the field of perinatal mental health highlight the importance of risk factors such as BDs, anxiety disorders, attachment insecurity, and neuroticism. This closer examination of factors that relate to individual personality traits represents an evolution from an earlier period in which unipolar history and social stressors were more heavily emphasized. The new emphasis on personality traits holds the promise for more accurate, individually tailored risk assessments by clinicians.

At the same time, recognition of the importance of early detection has been growing, as underlined by the recent release of guidelines from several bodies of experts who recommend increased attention to careful and regular screening for mood disorders and comorbid anxiety disorders in perinatal women. Although “universal screening” recommendations represent an advancement in early recognition and treatment, more research on susceptibility factors is needed so that high-risk groups can be easily identified through targeted screening practices.

There have been several important additions to the evolving conversation about the relative contributions of maternal mental illness versus psychotropic medication to obstetric, neonatal, and childhood outcomes. On the whole, these highlight the morbidity associated with maternal mental illness to a greater degree than has been previously recognized. The question of whether medication can mitigate these effects is still an open one. Recent work suggests that this may be true for at least some outcomes with respect to the use of SRI antidepressants for depression or anxiety but may not be true for the use of mood stabilizers or antipsychotics in women with BD.

For future research, questions remain regarding the respective roles of maternal mental illness and psychiatric medications in obstetrical and infant outcomes, and future studies must control for frequently unmeasured differences between groups, such as confounding by intention, family history of psychiatric illness, and developmental disorders. Larger and more carefully controlled studies of long-term neurodevelopmental outcomes in children are also lacking, particularly so for mood stabilizers and antipsychotics. Another unanswered question concerns the potential utility of tapering or briefly discontinuing antidepressants toward the end of pregnancy, as the most well-established adverse effects of medication (reduced term of gestation, pulmonary hypertension of the newborn, and neonatal adaptation) are all associated with third-trimester exposure. So far, data to inform this approach are lacking.