Faculty Bibliography

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.

OBJECTIVES/OBJECTIVE:Intergenerational transmission of trauma occurs when the effects of childhood maltreatment (CM) influence the next generation's development and health; prenatal programming via maternal mood symptoms is a potential pathway. CM is a risk factor for bipolar disorder which is present in 1.8% of pregnant women. Mood symptoms are likely to increase during pregnancy, particularly for those with a history of CM. We examined whether there was evidence for intergenerational transmission of trauma in utero in this population, and whether maternal mood was a transmission pathway. METHODS:CM and maternal mood were self-reported by N = 82 pregnant women in treatment for bipolar disorder. Fetal heart rate variability (FHRV) was measured at 24, 30, and 36 weeks' gestation. Gestational age at birth and birth weight were obtained from medical charts. RESULTS:A cluster analysis yielded two groups, Symptom+ (18.29%) and Euthymic (81.71%), who differed on severe mood symptoms (p < 0.001) but not on medication use. The Symptom+ group had more CM exposures (p < 0.001), a trend of lower FHRV (p = 0.077), and greater birth complications (33.3% vs. 6.07% born preterm p < 0.01). Maternal prenatal mood mediated the association between maternal CM and birth weight in both sexes and at trend level for gestational age at birth in females. CONCLUSIONS:This is the first study to identify intergenerational effects of maternal CM prior to postnatal influences in a sample of pregnant women with bipolar disorder. These findings underscore the potential enduring impact of CM for women with severe psychiatric illness and their children.

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.

BACKGROUND:Preliminary country-specific reports suggest that the COVID-19 pandemic has a negative impact on the mental health of the healthcare workforce. In this paper, we summarize the protocol of the COVID-19 HEalth caRe wOrkErS (HEROES) study, an ongoing, global initiative, aimed to describe and track longitudinal trajectories of mental health symptoms and disorders among health care workers at different phases of the pandemic across a wide range of countries in Latin America, Europe, Africa, Middle-East, and Asia. METHODS:Participants from various settings, including primary care clinics, hospitals, nursing homes, and mental health facilities, are being enrolled. In 26 countries, we are using a similar study design with harmonized measures to capture data on COVID-19 related exposures and variables of interest during two years of follow-up. Exposures include potential stressors related to working in healthcare during the COVID-19 pandemic, as well as sociodemographic and clinical factors. Primary outcomes of interest include mental health variables such as psychological distress, depressive symptoms, and posttraumatic stress disorders. Other domains of interest include potentially mediating or moderating influences such as workplace conditions, trust in the government, and the country's income level. RESULTS:As of August 2021, ~ 34,000 health workers have been recruited. A general characterization of the recruited samples by sociodemographic and workplace variables is presented. Most participating countries have identified several health facilities where they can identify denominators and attain acceptable response rates. Of the 26 countries, 22 are collecting data and 2 plan to start shortly. CONCLUSIONS:This is one of the most extensive global studies on the mental health of healthcare workers during the COVID-19 pandemic, including a variety of countries with diverse economic realities and different levels of severity of pandemic and management. Moreover, unlike most previous studies, we included workers (clinical and non-clinical staff) in a wide range of settings.

BACKGROUND:While the acquisition and application of Cognitive Behaviour Therapy (CBT) skills is a core component and likely mechanism of effect maintenance in all CBT-based treatments, the extent of post-therapeutic CBT skills usage among internet-delivered CBT (iCBT) clients remains under-researched. METHOD/METHODS:Nested within a pragmatic randomized controlled trial, 241 participants received an 8-week supported iCBT intervention for anxiety and/or depression and answered open-ended questions about their use and experience of CBT skills at 3-, 6-, 9-, and 12-month follow-up. Recurrent, cross-sectional qualitative analysis following the descriptive and interpretive approach was used to create a taxonomy, through which all qualitative data was coded. RESULTS:In total, 479 qualitative responses across 181 participants were analysed. Participants reported using a wide range of CBT skills and associated helpful and hindering experiences and impacts. The reasons for discontinued CBT skills usage were diverse, ranging from rare adverse effects to healthy adaptation. CONCLUSION/CONCLUSIONS:The study shows how clients receiving iCBT in routine care learn CBT skills during treatment and utilize them in productive ways post-treatment. Findings coincide with similar research in face-to-face CBT and may inform future research to drive innovation and iCBT intervention development.

Pregnancy is a critical time for the effects of environmental factors on children's development. The effect of added sugar intake on fetal development and pregnancy outcomes remains understudied despite increasing dietary intake in the United States. This study investigated the effect of added sugar on fetal programming by examining the association between maternal added sugar consumption, fetal movement, birth outcomes, and placental DNA methylation. Further, primary human fibroblasts were cultured under normal or high glucose conditions to assess the effect of high glucose exposure on cells' DNA methylation. We found that higher added sugar intake across pregnancy was associated with reduced 3rd-trimester fetal movement (p < .05) and shorter gestation (p < .01). Our sample size was not powered to detect the alteration of individual placental CpG with genome-wide significance. However, a secondary analysis suggested that added sugar consumption was associated with differential methylation of functionally related gene families across pregnancy. Consistent with this, high glucose exposure in primary cultured human fibroblasts altered the methylation of 17% of all CpGs, providing converging evidence for an effect of sugar on DNA methylation. Our results suggest that diets high in added sugar during pregnancy may have implications for offspring health via prenatal programming effects measurable before birth.

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.