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

Abstract

Purpose of Review-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. Recent Findings-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. Summary-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.

Effects of inflammation on the kynurenine pathway in schizophrenia — a systematic review

“…5 Center for Mind, Brain and Behavior (CMBB), Hans-Meerwein-Strasse 6, Marburg 35043, Hessen, Germany. 6 Collaborative Research Center 936 (SFB936) -Project C6 -Third Funding Period, Justus-Liebig University, Klinikstrasse 36, Giessen 35392, Hessen, Germany.…”

“…The model implies that genetic makeup predisposes the subject to be easily affected by stress, which would show inflammatory responses later in life [5]. A review by Lipner et al has concluded that prenatal maternal stress (e.g., prenatal infection/inflammation, decreased fetal growth, hypoxia-related obstetric complications) has been linked to the development of schizophrenia in offspring [6].…”

Becoming Stressed: Does the Age Matter? Reviewing the Neurobiological and Socio-Affective Effects of Stress throughout the Lifespan

“…Prenatal stress refers to the stress suffered by mothers during the gestational period that affects the offspring [31]. In humans, it has been demonstrated that prenatal exposure to unpredictable or chronic stressors, such as adverse life events, natural disasters or social pressures [34,35], increases the risk of suffering several psychopathologies, including schizophrenia [36][37][38], ASD [39,40], and major depression-and anxiety-related disorders [41]. Importantly, recent studies have confirmed what has long been theorized, but not yet observed in humans: that stress suffered during pregnancy is reflected in the connectional characteristics of the offspring's brain, independent of the influences of the postnatal environment [42].…”

Ecosystem approaches to the risk for schizophrenia

“…Studying the single contributions of specific environmental exposures in the pathogenesis of schizophrenia is challenging, as these factors are dynamically interconnected and interdependent over time. Prenatal maternal stress, for example, may increase the risk for schizophrenia in offspring through maternal subjective distress, obstetrical complications, health-impairing behaviors, or other pathways (King et al, 2010;Lipner et al, 2019). These pathways converge downstream to biological mechanisms such as maternal immune activation (Lipner et al, 2019).…”

“…Prenatal maternal stress, for example, may increase the risk for schizophrenia in offspring through maternal subjective distress, obstetrical complications, health-impairing behaviors, or other pathways (King et al, 2010;Lipner et al, 2019). These pathways converge downstream to biological mechanisms such as maternal immune activation (Lipner et al, 2019). Further, prenatal maternal stress, such as daily life hassles, may also be a proxy variable for inheritable or familial vulnerability factors (King et al, 2010).…”