Affiliations: Department of Psychiatry, University of Cambridge,
Cambridge, UK | West Suffolk Hospital, Norfolk and Suffolk NHS
Foundation Trust, Suffolk, UK
Note: [] Correspondence: Dr. Golam Khandaker, Department of Psychiatry,
University of Cambridge, Box 189, Addenbrooke's Hospital, Cambridge CB2 2QQ,
UK. Tel.: +44 1223 768510; Fax: +44 1223 336968; E-mail:
[email protected]
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).
