Gene-Environment Interaction and Covariation in Schizophrenia: The Role of Obstetric Complications

• Published in: Schizophrenia bulletin 2008-11, Vol.34 (6), p.1083-1094
• Main Authors: Mittal, Vijay A., Ellman, Lauren M., Cannon, Tyrone D.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Analysis of Variance; Brain - physiopathology; Female; Fetal Hypoxia - diagnosis; Fetal Hypoxia - physiopathology; Gene Expression - genetics; Genetic Predisposition to Disease - genetics; Genetic Predisposition to Disease - psychology; Gestational Age; Humans; Infant, Newborn; Obstetric Labor Complications - diagnosis; Obstetric Labor Complications - physiopathology; Phenotype; Pregnancy; Pregnancy Complications, Infectious - diagnosis; Pregnancy Complications, Infectious - physiopathology; Pregnancy Complications, Infectious - psychology; Risk Factors; Schizophrenia - diagnosis; Schizophrenia - genetics; Schizophrenia - physiopathology; Schizophrenic Psychology; Social Environment; Stress, Psychological - complications; Theme: Schizophrenia Aetiology: From G to GxE Guest Editor: Jim van Os and Robin Murray; Young Adult
• ISSN: 0586-7614; 1745-1701
• DOI: 10.1093/schbul/sbn080

While genetic factors account for a significant proportion of liability to schizophrenia, a body of evidence attests to a significant environmental contribution. Understanding the mechanisms through which genetic and environmental factors coalesce in influencing schizophrenia is critical for elucidating the pathways underlying psychotic illness and for developing primary prevention strategies. Although obstetric complications (OCs) remain among the most well-documented environmental indicators of risk for schizophrenia, the pathogenic role they play in the etiology of schizophrenia continues to remain poorly understood. A question of major importance is do these factors result from a genetic diathesis to schizophrenia (as in gene-environment covariation), act additively or interactively with predisposing genes for the disorder in influencing disease risk, or independently cause disease onset? In this review, we evaluate 3 classes of OCs commonly related to schizophrenia including hypoxia-associated OCs, maternal infection during pregnancy, and maternal stress during pregnancy. In addition, we discuss several mechanisms by which OCs impact on genetically susceptible brain regions, increasing constitutional vulnerability to neuromaturational events and stressors later in life (ie, adolescence), which may in turn contribute to triggering psychosis.