Journal
TRENDS IN NEUROSCIENCES
Volume 30, Issue 4, Pages 142-149Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tins.2007.02.002
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- Wellcome Trust Funding Source: Medline
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Converging evidence suggests that the regulation of glycogen synthase kinase 3 (GSK-3) might be important in schizophrenia. Atypical and typical antipsychotic drugs alter GSK-3 activity, as do drugs that induce psychosis. GSK-3 regulatory pathways are altered in schizophrenia, and many of the genes associated with schizophrenia directly or indirectly regulate GSK-3 activity. We propose a variant on the neurodevelopment and dopamine hypotheses of schizophrenia, whereby (i) an early dysfunction in GSK-3 regulation has neurodevelopmental consequences that predispose to disease and (ii) dysfunction in GSK-3 regulation in the adult brain alters dopamine signalling events, causing psychotic symptoms and cognitive dysfunction. If, as we suggest, GSK-3 regulation is crucial to schizophrenia, the Wnt and insulin signalling pathways become targets for therapy.
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