Prenatal exposure to infection: A primary mechanism for abnormal dopaminergic development in schizophrenia

Urs Meyer*, Joram Feldon

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Rationale: Prenatal exposure to infection is a notable environmental risk factor in the development of schizophrenia. One prevalent hypothesis suggests that infection-induced disruption of early prenatal brain development predisposes the organism to long-lasting structural and functional brain abnormalities. Many of the prenatal infection-induced functional brain abnormalities appear to be closely associated with imbalances in the mesocorticolimbic dopamine system in adult life, suggesting that disruption of functional and structural dopaminergic development may be at the core of the developmental neuropathology associated with psychosis-related abnormalities induced by prenatal exposure to infection. Objectives: In this review, we integrate recent findings derived from experimental models in animals with parallel research in humans which supports this hypothesis. We thereby highlight the developmental perspective of abnormal DA functions following in-utero exposure to infection in relation to the developmental and maturational mechanisms potentially involved in schizophrenia. Results: Experimental investigations show that early prenatal immune challenge can lead to the emergence of early structural and functional alterations in the mesocorticolimbic DA system, long before the onset of the full spectrum of psychosis-associated behavioral and cognitive abnormalities in adulthood. Conclusions: Dopaminergic mal-development in general, and following prenatal immune activation in particular, may represent a primary etiopathological mechanism in the development of schizophrenia and related disorders. This hypothesis differs from the view that dopaminergic abnormalities in schizophrenia may be secondary to abnormalities in other brain structures and/or neurotransmitter systems. The existence of primary dopaminergic mechanisms may have important implications for the identification and early treatment of individuals prodromally symptomatic for schizophrenia.

Original languageEnglish
Pages (from-to)587-602
Number of pages16
JournalPsychopharmacology
Volume206
Issue number4
DOIs
StatePublished - Nov 2009
Externally publishedYes

Keywords

  • Animal model
  • Cytokines
  • Dopamine
  • Limbic system
  • NMDA
  • Neurodevelopment
  • Prefrontal cortex
  • Prodromal
  • Psychosis
  • Striatum

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