Prenatal Maternal Stress and the Cascade of Risk to Schizophrenia Spectrum Disorders in Offspring.

Abstract

Disruptions in fetal development (via genetic and environmental pathways) have been consistently associated with risk for schizophrenia in a variety of studies. Although multiple obstetric complications (OCs) have been linked to schizophrenia, this review will discuss emerging evidence supporting the role of prenatal maternal stress (PNMS) in the etiology of schizophrenia spectrum disorders (SSD). In addition, findings linking PNMS to intermediate phenotypes of the disorder, such as OCs and premorbid cognitive, behavioral, and motor deficits, will be reviewed. Maternal immune and endocrine dysregulation will also be explored as potential mechanisms by which PNMS confers risk for SSD. PNMS has been linked to offspring SSD; however, findings are mixed due to inconsistent and retrospective assessments of PNMS and lack of specificity about SSD outcomes. PNMS is also associated with various intermediate phenotypes of SSD (e.g., prenatal infection/inflammation, decreased fetal growth, hypoxia-related OCs). Recent studies continue to elucidate the impact of PNMS while considering the moderating roles of fetal sex and stress timing, but it is still unclear which aspects of PNMS (e.g., type, timing) confer risk for SSD specifically. PNMS increases risk for SSD, but only in a small portion of fetuses exposed to PNMS. Fetal sex, genetics, and other environmental factors, as well as additional pre- and postnatal insults, likely contribute to the PNMS-SSD association. Longitudinal birth cohort studies are needed to prospectively illuminate the mechanisms that account for the variability in outcomes following PNMS.