Faculty Bibliography

Human and animal neuroscience studies support the view that plastic shifts occur in the brain during pregnancy that support the emergence of new maternal behaviours. The idea of adaptive plasticity in pregnancy is at odds with the notion of "baby brain", in which pregnant women describe the onset of forgetfulness. While inconsistent evidence for memory deficits during pregnancy has been reported, few studies have investigated spatial associative memory (which is consistently enhanced in studies of pregnant rodents). Moreover, most studies assess domain-general stimuli, which might miss adaptations specific to parent-relevant stimuli. In the present study, we examined the retention of spatial associative memory for parenting-relevant and non-parenting-relevant stimuli across 4-weeks in a sample of women in their third trimester of pregnancy, and compared their performance to a sample of never pregnant women. We demonstrated that relative to never pregnant women, pregnant women exhibited enhanced long-term retention of object-scene-location associations (spatial associative memory), as well as better initial learning about parenting-relevant, relative to non-parenting-relevant, stimuli. Thus, similar to studies in rodents, cognitive improvements were seen during pregnancy in humans, and those improvements were specific to the domain of spatial associative retention, and in the recognition of stimuli relevant to parenting.

Inflammatory processes are a candidate mechanism by which early adversity may be biologically embedded and subsequently lead to poorer health outcomes; in pregnancy, this has been posited as a pathway for intergenerational transmission of adversity. Studies in non-pregnant adults suggest that factors such as mood, diet, BMI, and social support may moderate associations between childhood trauma history and inflammation in adulthood, though few studies have examined these associations among pregnant women. In a sample of healthy pregnant women (N = 187), we analyzed associations between maternal childhood adversity, including maltreatment and non-optimal caregiving experiences, with circulating Interleukin-6 (IL-6) levels during trimesters 2 (T2) and 3 (T3) of pregnancy. We also assessed whether these associations were moderated by psychosocial and lifestyle factors including depressive symptoms, social support, physical activity, and diet quality. History of childhood maltreatment was not associated with IL-6 in either T2 or T3 of pregnancy, either independently or in interaction with depressive symptom severity. However, in there was a significant positive association between childhood maltreatment and IL-6 in Trimester 2 in the context of poorer diet quality (p = 0.01), even after adjusting for BMI. Additionally, the quality of caregiving women received in childhood was associated with levels of IL-6 in Trimester 3, but only via interaction with concurrent depressive symptoms (p = 0.02). These findings provide evidence that for those with a history of childhood adversity, levels of inflammatory cytokines in pregnancy may be more sensitive to depressive symptoms and diet quality.

This chapter provides an overview of current research discoveries beginning to uncover the neurobiology of maternal mental illness. Results are described according to standard diagnostic categories (specifically, perinatal depression, perinatal anxiety and OCD, postpartum psychosis and bipolar disorder, and trauma and posttraumatic stress disorder), yet we aim to put this approach in context with the introduction of a classification model for psychiatric research, the research domain criteria, gaining traction in basic and clinical translational fields. We first review a new area of study, the neuroplasticity of the pregnant and postpartum brain, as work here has relevance for understanding the pathophysiology of mental disorders and may provide clues to changes in brain functioning that are related to compromised parenting in the context of postpartum depression. We next provide background information on neuroendocrine and immune changes during pregnancy and, to a lesser extent, the postpartum period, as alterations in these systems are significantly implicated in underlying neurobiology of mental illness for peripartum women. Our discussion of the major mental illnesses for pregnant and postpartum women includes neuroendocrine changes, neuroinflammation, and neurotransmitter alterations, as well as circuit dysfunction. Overall, remarkable progress has been made in identifying variations in neurobiology (and related systems) involved in maternal mental illness; yet, it is clear that, as classified with standard diagnostic systems, these are heterogeneous disorders and there is individual variability in the alterations in neurobiology for the same illness.

Maternal prenatal stress influences offspring neurodevelopment and birth outcomes including the ratio of males to females born; however, there is limited understanding of what types of stress matter, and for whom. Using a data-driven approach with 27 variables from questionnaires, ambulatory diaries, and physical assessments collected early in the singleton pregnancies of 187 women, 3 latent profiles of maternal prenatal stress emerged that were differentially associated with sex at birth, birth outcomes, and fetal neurodevelopment. Most women (66.8%) were in the healthy group (HG); 17.1% were in the psychologically stressed group (PSYG), evidencing clinically meaningful elevations in perceived stress, depression, and anxiety; and 16% were in the physically stressed group (PHSG) with relatively higher ambulatory blood pressure and increased caloric intake. The population normative male:female secondary sex ratio (105:100) was lower in the PSYG (2:3) and PHSG (4:9), and higher in the HG (23:18), consistent with research showing diminished male births in maternal stress contexts. PHSG versus HG infants were born 1.5 wk earlier (P < 0.05) with 22% compared to 5% born preterm. PHSG versus HG fetuses had decreased fetal heart rate-movement coupling (P < 0.05), which may indicate slower central nervous system development, and PSYG versus PHSG fetuses had more birth complications, consistent with previous findings among offspring of women with psychiatric illness. Social support most strongly differentiated the HG, PSYG, and PHSG groups, and higher social support was associated with increased odds of male versus female births. Stress phenotypes in pregnant women are associated with male vulnerability and poor fetal outcomes.

PURPOSE OF REVIEW:To synthesize and critically examine recent evidence regarding associations between immune system activity and perinatal depression. RECENT FINDINGS:Despite a significant number of studies assessing potential immunological markers of perinatal depression, it does not appear that levels of any individual pro- or anti-inflammatory marker is a useful predictor of perinatal depression. Some recent studies have observed differences in overall immune system functioning and adaptation across this period, taking into account multiple pro- and anti- inflammatory markers. Furthermore, there is evidence for interactions between depression and maternal psychosocial factors. Immune system functioning may be a mechanism through which social determinants of health contribute to risk for perinatal depression. There is substantial evidence implicating dysregulated immune activity in perinatal depression, yet little clarity regarding a consistent immune profile, especially based on analysis of circulating peripheral cytokines.

Healthcare workers (HCWs) were at increased risk for mental health problems during the COVID-19 pandemic, with prior data suggesting women may be particularly vulnerable. Our global mental health study aimed to examine factors associated with gender differences in psychological distress and depressive symptoms among HCWs during COVID-19. Across 22 countries in South America, Europe, Asia and Africa, 32,410 HCWs participated in the COVID-19 HEalth caRe wOrkErS (HEROES) study between March 2020 and February 2021. They completed the General Health Questionnaire-12, the Patient Health Questionnaire-9 and questions about pandemic-relevant exposures. Consistently across countries, women reported elevated mental health problems compared to men. Women also reported increased COVID-19-relevant stressors, including insufficient personal protective equipment and less support from colleagues, while men reported increased contact with COVID-19 patients. At the country level, HCWs in countries with higher gender inequality reported less mental health problems. Higher COVID-19 mortality rates were associated with increased psychological distress merely among women. Our findings suggest that among HCWs, women may have been disproportionately exposed to COVID-19-relevant stressors at the individual and country level. This highlights the importance of considering gender in emergency response efforts to safeguard women's well-being and ensure healthcare system preparedness during future public health crises.

IMPORTANCE/UNASSIGNED:General trauma is the leading cause of nonobstetric maternal morbidity and mortality, affecting approximately 8% of all pregnancies. Pregnant women with traumatic brain injury (TBI) face high morbidity and mortality rates, requiring complex management due to physiological changes, teratogenic risks of treatments, and the need for fetal monitoring. OBJECTIVES/UNASSIGNED:To assess the consequences of TBI during pregnancy on maternal and fetal outcomes and to evaluate management strategies to inform clinical decision-making. EVIDENCE REVIEW/UNASSIGNED:A systematic literature search was conducted on January 12, 2024, in PubMed, Web of Science, and PsycInfo to identify articles published in English, German, or Spanish between January 1, 1990, and December 31, 2023, that included at least 1 pregnant individual with TBI. Peer-reviewed, human-based studies with original data on maternal and fetal outcomes were included. Reviews, meta-analyses, and nonhuman studies were excluded. Two independent reviewers screened abstracts and full-text articles. Study characteristics, pregnancy outcomes (maternal and fetal), management methods, and authors' conclusions were extracted. Risk of bias was assessed by 2 reviewers, with interrater agreement measured using Cohen κ. Disagreements were resolved through discussion. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed. FINDINGS/UNASSIGNED:This systematic review included 16 articles involving a total of 4112 individuals (mean maternal age, 26.9 years; range, 16-47 years) who experienced TBI during pregnancy (mean gestational age at injury, 24 weeks; range, 3-38 weeks). The articles comprised 10 case reports, 2 case series, and 4 cohort studies. Motor vehicle crashes were the most common cause of injury, reported in 12 articles. The average Glasgow Coma Scale score ranged from 3 to 15 across all individuals. Conservative management was reported in 7 case patients, whereas surgery was performed in 6 case patients. Maternal outcomes ranged from functional recovery to severe cognitive impairment, and fetal outcomes varied from stable to severe adverse outcomes, including stillbirth and death. Risk of bias assessment indicated moderate to good methodological validity overall, but most articles demonstrated poor quality of evidence. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this review, no definitive association between TBI during pregnancy and maternal or fetal outcomes was found owing to conflicting findings, poor to moderate study quality, and limited evidence. Although some articles suggested increased risks such as placental abruption and cesarean delivery, the findings remained inconclusive. The findings of this review underscore the need for high-quality research, standardized reporting, and rigorous methodology to improve data reliability. Future research should focus on developing consensus-driven, multidisciplinary management strategies to improve maternal and fetal outcomes.