Neurodevelopment in Schizophrenia: The Role of the Wnt Pathways

Elisa      Ambrosi; Gabriele      Sani; Paolo      Girardi; Ferdinando      Nicoletti; Marta      Motolese; Delfina      Janiri; Giovanni      Manfredi; Emanuela      Danese; Lavinia   De   Chiara; Valeria      Savoja; Alessio      Simonetti; Isabella      Panaccione; Ilaria      Cuomo; Federica      Caccia; Daniele      Serata; Chiara      Brugnoli; Chiara      Rapinesi; Antonio   Del   Casale; Giorgio   D.   Kotzalidis; Alberto   Maria   Forte; Flavia      Napoletano

Abstract

Objectives. To review the role of Wnt pathways in the neurodevelopment of schizophrenia.

Methods: Systematic PubMed search, using as keywords all the terms related to the Wnt pathways and crossing them with each of the following areas: normal neurodevelopment and physiology, neurodevelopmental theory of schizophrenia, schizophrenia, and antipsychotic drug action.

Results: Neurodevelopmental, behavioural, genetic, and psychopharmacological data point to the possible involvement of Wnt systems, especially the canonical pathway, in the pathophysiology of schizophrenia and in the mechanism of antipsychotic drug action. The molecules most consistently found to be associated with abnormalities or in antipsychotic drug action are Akt1, glycogen synthase kinase3beta, and beta-catenin. However, the extent to which they contribute to the pathophysiology of schizophrenia or to antipsychotic action remains to be established.

Conclusions: The study of the involvement of Wnt pathway abnormalities in schizophrenia may help in understanding this multifaceted clinical entity; the development of Wnt-related pharmacological targets must await the collection of more data.

Keywords: Antipsychotic Drugs; Neurodevelopment; Schizophrenia; Wingless (Wnt) signalling.

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