Prenatal maternal influenza and schizophrenia in offspring: What does this tell us about fetal programming of chronic disease?

Abstract

Accumulating evidence suggests that chronic diseases, physical as well as neuropsychiatric, may have their origins in early life. Alterations in fetal development have been reported to be associated with an increased risk of subsequent cardiovascular and metabolic disorders. This has been formulated as the fetal or developmental programming hypothesis. Schizophrenia is a severe and chronic neuropsychiatric illness of teenage and adult life. Birth cohort studies have reported low birth weight, delays in attaining motor milestones, and deficits in premorbid cognitive and social functioning as factors associated with, and possible risk factors for future schizophrenia. These provide empirical support for the currently widely accepted neurodevelopmental hypothesis of schizophrenia, where abnormalities in early brain development contribute to the evolution of the disorder. Interference with brain development from infections in early life is in line with a neurodevelopmental view of schizophrenia. Prenatal maternal infections such as influenza have been linked with increased risk of both childhood sub-clinical psychotic symptoms and adult schizophrenia. Prenatal maternal infections can increase fetal exposure to excessive maternal glucocorticoids. This can reprogram the hypothalamic-pituitary-adrenal axis leading to increased risk of several chronic diseases including schizophrenia. In this review we focus on epidemiological and preclinical studies concerning prenatal maternal influenza and risk of both childhood psychotic symptoms and later development of schizophrenia in the offspring. We discuss these findings in light of the fetal programming hypothesis, which points towards common links, in early life, between chronic diseases, physical (such as hypertension and type-two diabetes) and neuropsychiatric (such as schizophrenia).

Keywords

Schizophrenia - influenza - pregnancy - prenatal - infection - fetal programming - chronic disease - childhood development