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 wellcharacterized 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.

COVID-19 Infection During Pregnancy and Risk of Neurodevelopmental Disorders in Offspring: Time for Collaborative Research

“…A number of different mechanisms have been proposed to explain how maternal infection may interfere with brain development in the offspring: 1) systemic allostatic overload with loss of structural and functional placenta integrity, 2) activation of the maternal and fetal immune responses with the production of neuronal antibodies and proinflammatory cytokines, and 3) interference in the fetal neurodevelopment by direct brain infection ( 3 , 6 , 7 , 8 ). However, there is currently limited evidence regarding the risk of intrauterine vertical transmission of SARS-CoV-2, and whether the virus has neuroinvasive potential via retrograde axonal transport from peripheral nerves or via a hematogenous route is the subject of ongoing debate ( 1 , 9 ).…”

“…Thus, attention should focus on how COVID-19 infection could affect the fetal brain through the loss of placental integrity or activation of immune/inflammatory response. Special consideration should be given to the role of cytokines and activation of fetal microglia, mast cells, and astrocytes; changes in placental neurotransmitter production; the consequences of prolonged fever, hypoxia, hypertension, electrolyte abnormalities, and changes in the microbiome; and the effects of medication employed to treat the infection ( 6 , 8 , 10 ). It should further be noted that most of the data currently available concern neonatal and delivery outcomes from low-quality studies of pregnant women infected by COVID-19 in their third trimesters ( 9 ).…”

Starting strong: Dietary, behavioral, and environmental factors that promote “strength” from conception to age 2 years

“…To counter risk, the assessment of the pregnant woman begins with a health screening, including for existing clinical conditions, such as hypertension and diabetes, anemia, asthma, depression, and autoimmune diseases, and the extent of their control. Red flags are noted that may threaten the outcome of the pregnancy, such as tobacco, drugs, or alcohol use, poor maternal dietary habits, physical inactivity, and preconception over-or under-weight (Rasmussen and Yaktine 2009;Kwon and Kim 2017;Khambadkone et al 2020). By measuring and monitoring the mother's health, lifestyle habits, and weight gain, and by measuring fetal growth relative to postconception dates, using physical examination and ultrasound, the clinician can minimize potential problems for the fetus.…”

“…The mother's physical and mental status throughout pregnancy will determine the in-utero environment of the growing fetus (Choi and Friso 2010;Kwon and Kim 2017;Shankar et al 2018). Contributors to adverse maternal well-being will alter fetal development, resulting in a high risk for later chronic diseases, including cardiovascular diseases, metabolic diseases, cancers, obesity, and even behavioral disorders (Larque et al 2019;Khambadkone et al 2020). Epigenetic factors remain predominant stimuli for optimal growth and development in the months and years following birth (Shankar et al 2018).…”

Maternal High-Fat Diet Induces Long-Lasting Defects in Bone Structure in Rat Offspring Through Enhanced Osteoclastogenesis

“…In this study, we examined the effects of a maternal stressor on the maintenance of bone structure in offspring. The intrauterine environment is designed to support fetal development, Priyanka Kushwaha and Seva G. Khambadkone but increasing epidemiologic and experimental evidence indicates that maternal stressors during this period or during early postnatal life can pattern susceptibility for or severity of disease in offspring [4,5]. Referred to as the Developmental Origins of Health and Disease (DOHaD) hypothesis, maternal stressors like under-or over-nutrition, trauma, or infection are associated with increased prevalence of metabolic dysfunction, cardiovascular disease, and mental illness in progeny.…”