From synapses to symptoms in maternal mental health during pregnancy and postpartum

Pregnancy is one of the most dynamic and plastic periods in a woman's life, offering a remarkable potential for physiological adaptation. Although in most cases occurring without serious complications, a substantial proportion of women are affected by "postpartum blues" or the more pervasive postpartum depression or psychosis. The mechanisms are elusive, but may partly reflect the cost of boosted brain plasticity (i.e., the potential for neural change in response to changing environmental demands) during pregnancy. The current research project will utilize recent technological advances to test the conjecture that increased brain plasticity during pregnancy not only promotes environmental adaptation and attachment to the infant, but also increases susceptibility to psychopathology when combined with specific genetic risk and environmental triggers. Specifically, we will test the hypothesis that combination of changes in (1) brain plasticity, (2) immune system regulation, and (3) gene expression are associated both with a healthy adaptation to the changing environment and increased risk for mental disorders in some mothers. During the fourth year of the project we have focused on follow-ups of earlier examinations, which includes imaging of the structure and function of the maternal brain using MRI and EEG, monitor physical activity, sleep, and emotional states, probe immune system and inflammatory responses, and assess sub-clinical and diagnostic symptoms. Our combination of careful phenotyping and advanced statistical tools will allow us to assess maternal brain changes in detail and predict clinical trajectories. By now, we have received 844 visits at the EEG-lab, 606 visits at the MRI-scanner, and 1014 blood sampling visits. In addition, we have started quality control and preprocessing of the acquired data. The results will inform models of maternal mental health, with important implications for our understanding of mechanisms that increase or decrease risk for mental disorders in general, which is needed to move mental health research from a descriptive to a predictive framework required for personalized interventions in maternal health care.

Pregnancy is one of the most dynamic and plastic periods in a woman's life, offering a remarkable potential for physiological adaptation. Although in most cases occurring without complications, a substantial proportion of women are affected by "postpartum blues" or the more pervasive postpartum depression or psychosis. The mechanisms are elusive, but partly reflect the cost of boosted brain plasticity during pregnancy. We utilize recent advances to test the conjecture that increased brain plasticity during pregnancy not only promotes adaptation and attachment, but also increases susceptibility to psychopathology when combined with genetic risk and environmental triggers. We propose that a multi-level investigation with this dark side of brain plasticity as the axis mundi will add a mechanistic understanding of maternal mental health. We combine novel approaches for in vitro neuronal characterization using iPSC-based techniques and prospective in-vivo imaging of the structure, function and biochemistry of the maternal brain. We monitor physical activity, sleep, and emotional states, probe immune system and inflammatory responses, and assess sub-clinical and diagnostic symptoms. We perform full-genome chipping and estimate polygenic risk for a variety of traits, and assess changes in gene expression throughout pregnancy and postpartum. Our big data approach uses advanced statistical tools to estimate normative models based on huge datasets to form individual predictions in our prospective cohorts. This unique combination of data mining and careful phenotyping allows us to test if maternal brain changes mirror other transformative phases or disorders and predict clinical trajectories. Identifying such common and unique mechanisms is a critical step towards an empirical nosology of complex traits, which is needed to move mental health research from a descriptive to a predictive framework required for personalized interventions in maternal health care.