Early Environmental Upheaval and the Risk for Schizophrenia

Abstract

Why does prenatal exposure to wars, natural disasters, urbanicity, or winter increase the risk for schizophrenia? Research from the last two decades has provided rich insight about the underlying chains of causation at play during environmental upheaval, from conception to early infancy. In this review, we appraise the evidence linking schizophrenia spectrum disorder to prenatal maternal stress, obstetric complications, early infections, and maternal nutrition and other lifestyle factors. We discuss putative mechanisms, including the maternal stress system, perinatal hypoxia, and maternal–offspring immune activation. We propose that gene–environment interactions, timing during development, and sex differentiate the neuropsychiatric outcomes. Future research should pursue the translation of animal studies to humans and the longitudinal associations between early exposures, intermediate phenotypes, and psychiatric disorders. Finally, to paint a comprehensive model of risk and to harness targets for prevention, we argue that risk factors should be situated within the individual's personal ecosystem. Expected final online publication date for the Annual Review of Clinical Psychology, Volume 17 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Longitudinal Trajectories of Food Insecurity in Childhood and Their Associations With Mental Health and Functioning in Adolescence

“…To yield more tangible differences in mental health, food insecurity may require interaction with other forms of adversity or genetic factors. 52 , 53 , 54 …”

“…Age at exposure to food insecurity (eg, infancy vs adolescence) may also be associated with outcomes. 52 , 57 Because of sparse, overlapping exposure data, we were unable to explore this in the cohort. Our assessment of food insecurity began at 1.5 years of age; therefore, the prevalence and contribution to outcomes of earlier (eg, prenatal) onset of food insecurity could not be examined.…”

Age- and sex-specific associations between risk scores for schizophrenia and self-reported health in the general population

“…Using linear mixed models, we estimated the trend between PRS-SCZ or ES-SCZ and the outcomes at various ages, including linear and quadratic effects of age on these trends only, and not for mental health. Ultimately, mechanisms for these sex differences are complex and may include multiple social and environmental factors, genes, neurodevelopmental trajectories, immune responses, and gonadal hormones, and the relative contribution of these mechanisms may be heterogeneous depending on population characteristics, measurements, and outcome selection [11,31].…”

“…However, the health correlates of PRS-SCZ and ES-SCZ may vary as a function of age and sex [9][10][11]. For example, in non-clinical samples, PRS-SCZ seems to be more strongly related to cognition during late life [12], and its associations with cognitive task performance and schizotypy may be male-specific [13,14].…”

Association between exposome score for schizophrenia and functioning in first-episode psychosis: results from the Athens first-episode psychosis research study

“…Future studies should conduct long-term follow-up replications to examine the stability of our findings across time. Fourth, deep clinical phenotyping and rich environmental assessment allowed for inclusion of several associated alternative explanatory variables to test the robustness of the association between ES-SCZ and functioning independent of clinical and other environmental features, such as pre-and perinatal risk factors (Davies et al, 2020;Paquin, Lapierre, Veru, & King, 2021). However, there might still be unmeasured confounding considering the extensive list of factors associated with functioning.…”