Maternal stressors and the developmental origins of neuropsychiatric risk

Abstract

The maternal environment during pregnancy is critical for fetal development and perinatal perturbations can prime offspring disease risk. Here, we briefly review evidence linking two well-characterized maternal stressors - psychosocial stress and infection - to increased neuropsychiatric risk in offspring. In the current climate of increasing obesity and globalization of the Western-style diet, maternal overnutrition emerges as a pressing public health concern. We focus our attention on recent epidemiological and animal model evidence showing that, like psychosocial stress and infection, maternal overnutrition can also increase offspring neuropsychiatric risk. Using lessons learned from the psychosocial stress and infection literature, we discuss how altered maternal and placental physiology in the setting of overnutrition may contribute to abnormal fetal development and resulting neuropsychiatric outcomes. A better understanding of converging pathophysiological pathways shared between stressors may enable development of interventions against neuropsychiatric illnesses that may be beneficial across stressors.

Keywords: Allostatic load; Anxiety; Autism spectrum disorders; Depression; Developmental origins of health and disease; Inflammation; Maternal diet; Maternal immune activation; Maternal obesity; Maternal stress; Neuropsychiatric risk; Schizophrenia.

Fig. 1.

Different maternal environmental stressors lead to common neuropsychiatric risk profiles in offspring. Epidemiological and animal model studies associate maternal stress, infection, and altered nutrition with increased risk for an overlapping range of neuropsychiatric outcomes in offspring, including cognitive impairment, anxiety, depression, schizophrenia, and autism spectrum disorders. Evidence suggests that these stressors act via converging pathophysiological pathways characterized by systemic allostatic overload across regulatory systems including the hypothalamic–pituitary–adrenal (HPA) axis, metabolic signaling, and inflammatory pathways. The placenta acts as an integrator and propagator of allostatic overload, not only communicating the maternal environment to the fetus but also altering its own structural and functional capacity in response. The developing fetus, patterned in an environment of dysregulation, is programmed towards increased neuropsychiatric risk. Created with BioRender.com.