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Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants
Published on: June 13, 2021
Maternal Perinatal Stress Trajectories and Negative Affect and Amygdala Development in Offspring
Mollie C Marr1, Alice M Graham1, Eric Feczko1
1Department of Behavioral Neuroscience (Marr, Graham, Sturgeon, Schifsky, Fair) and Department of Psychiatry (Graham, Fair), Oregon Health and Science University School of Medicine, Portland; Department of Psychiatry, Massachusetts General Hospital, Boston (Marr); Department of Psychiatry, McLean Hospital, Belmont, Mass. (Marr); Masonic Institute for the Developing Brain, Institute of Child Development (Fair), and Department of Pediatrics (Feczko, Fair), University of Minnesota, Minneapolis; Department of Psychology and Speech-Language Pathology, University of Turku, Turku, Finland (Nolvi, Korja); Institute of Medical Psychology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin (Nolvi, Entringer, Buss); Department of Neuroscience, Earlham College, Richmond, Ind. (Thomas); Development, Health, and Disease Research Program and Departments of Pediatrics, Psychiatry and Human Behavior, Obstetrics and Gynecology, and Epidemiology, University of California, Irvine, School of Medicine, Irvine (Rasmussen, Entringer, Wadhwa, Buss); Department of Pediatrics, University of California, Irvine, School of Medicine, Orange (Rasmussen, Entringer, Wadhwa, Buss); Departments of Psychiatry and Human Behavior (Entringer, Wadhwa), Obstetrics and Gynecology (Wadhwa), and Epidemiology (Wadhwa), University of California, Irvine, School of Medicine, Orange; FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, University of Turku (Korja, H. Karlsson, L. Karlsson); Centre for Population Health Research, University of Turku and Turku University Hospital (Korja, H. Karlsson, L. Karlsson); Department of Paediatrics and Adolescent Medicine (L. Karlsson) and Department of Psychiatry (H. Karlsson), Department of Clinical Medicine, Turku University Hospital and University of Turku; Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill (Gilmore); Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill (Styner).
Objective:
Maternal psychological stress during pregnancy is a common risk factor for psychiatric disorders in offspring, but little is known about how heterogeneity of stress trajectories during pregnancy affect brain systems and behavioral phenotypes in infancy. This study was designed to address this gap in knowledge.
Methods:
Maternal anxiety, stress, and depression were assessed at multiple time points during pregnancy in two independent low-risk mother-infant cohorts (N=115 and N=2,156). Trajectories in maternal stress levels in relation to infant negative affect were examined in both cohorts. Neonatal amygdala resting-state functional connectivity MRI was examined in a subset of one cohort (N=60) to explore the potential relationship between maternal stress trajectories and brain systems in infants relevant to negative affect.
Results:
Four distinct trajectory clusters, characterized by changing patterns of stress over time, and two magnitude clusters, characterized by severity of stress, were identified in the original mother-infant cohort (N=115). The magnitude clusters were not associated with infant outcomes. The trajectory characterized by increasing stress in late pregnancy was associated with blunted development of infant negative affect. This relationship was replicated in the second, larger cohort (N=2,156). In addition, the trajectories that included increasing or peak maternal stress in late pregnancy were related to stronger neonatal amygdala functional connectivity to the anterior insula and the ventromedial prefrontal cortex in the exploratory analysis.
Conclusions:
The trajectory of maternal stress appears to be important for offspring brain and behavioral development. Understanding heterogeneity in trajectories of maternal stress and their influence on infant brain and behavioral development is critical to developing targeted interventions.
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