GSK-3 and the neurodevelopmental hypothesis of schizophrenia

Nitsan Kozlovsky, R. H. Belmaker, Galila Agam

Research output: Contribution to journalReview articlepeer-review

127 Scopus citations


The Neurodevelopmental Hypothesis of schizophrenia suggests that interaction between genetic and environmental events occurring during critical early periods in neuronal growth may negatively influence the way by which nerve cells are laid down, differentiated and selectively culled by apoptosis. Recent advances offer insights into the regulation of brain development. The Wnt family of genes plays a central role in normal brain development. Activation of the Wnt cascade leads to inactivation of glycogen synthase kinase-3β (GSK-3β), accumulation and activation of β-catenin and expression of genes involved in neuronal development. Alteration in the Wnt transduction cascade, which may represent an aberrant neurodevelopment in schizophrenia, is discussed. Programmed cell death is also an essential component of normal brain development. Abnormal neuronal distribution found in schizophrenic patients' brains may imply aberrant programmed cell death. GSK-3 participates in the signal transduction cascade of apoptosis. The possible role of aberrant GSK-3 in the etiology of schizophrenia is discussed.

Original languageEnglish
Pages (from-to)13-25
Number of pages13
JournalEuropean Neuropsychopharmacology
Issue number1
StatePublished - 1 Jan 2002


  • Apoptosis
  • Glycogen synthase kinase-3 (GSK-3)
  • Neurodevelopmental hypothesis
  • Schizophrenia
  • Wnt signaling

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)


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