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

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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.

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Acknowledgements

The studies performed at the authors’ institute were supported by the Swiss Federal Institute of Technology (ETH) Zurich and the Swiss National Science Foundation (SNSF).

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  1. Laboratory of Behavioral Neurobiology, ETH Zurich, Schorenstrasse 16, 8603, Schwerzenbach, Switzerland

    Urs Meyer & Joram Feldon

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Meyer, U., Feldon, J. Prenatal exposure to infection: a primary mechanism for abnormal dopaminergic development in schizophrenia. Psychopharmacology 206, 587–602 (2009). https://doi.org/10.1007/s00213-009-1504-9

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