Pregnancy—A Critical Time for Mental Health : Interrogating Psychiatry with Microbiota-Gut-Brain Axis and Autonomic Nervous System Biomarkers

Abstract: Perinatal mood and anxiety disorders (PMADs) are common and impact the parent and child beyond the perinatal period of pregnancy and postpartum. The aim of this thesis was to study biomarkers that might reflect perinatal mental health. This work focused on multiple methods of mental health characterization and the autonomic nervous system as reflected by heart rate variability (HRV), the immune system, and the gut microbiome.Three observational longitudinal cohorts of pregnant individuals from three geographic regions were studied: 1) the Biology, Affect, Stress, Imaging and Cognition (BASIC) and the follow-up study U-BIRTH from Uppsala University Hospital; 2) the University of Illinois at Chicago (UIC) MoMent cohort; and 3) the University of North Carolina at Chapel Hill (UNC) cohort.The first paper assessed HRV before and after a mental task and in relation to psychiatric diagnoses, exposure to trauma, and self-report of mental distress. The second paper studied the Perceived Stress Scale (PSS-10) in relation to microbial composition and T-cell related cytokines and chemokines. The third paper studied the Edinburgh Postnatal Depression Scale (EPDS) in relation to whole genome sequencing and Gut Brain Modules for functioning. The fourth paper assessed trajectories of infant temperament in relation to depression and anxiety from the EPDS.The PSS-10 and the EPDS factored differently in the cohorts. HRV patterns differed based on anxiety disorder type, greater trait anxiety, and greater exposure to childhood traumatic eventsut microbiome data improved the prediction of PSS-10 self-efficacy; and self-efficacy was associated with a bacteria type more beneficial in the presence of dietary fiber that also associated with an immune factor important in immune tolerance. Greatest variation in microbial community functioning was due to cortisol degradation and synthesis of inositol, menaquinone, and the short chain fatty acid (SCFA) acetate. nxiety in pregnancy was associated with children who had higher levels of sensitivity and greater negative affectivity that increased over early life.These four papers highlight: 1) the course of mental health in pregnancy is critical to the development of parent and child; 2) the characterization of perinatal mental health requires a mix of methods that recognize there may be differences in the use of the methods based on the population; and 3) biomarkers of perinatal mental health need to reflect dynamic systems, and the components may not be as important as the patterns and interactions.