Low GSK-3 activity in frontal cortex of schizophrenic patients

N. Kozlovsky, R. H. Belmaker, G. Agam

Research output: Contribution to journalArticlepeer-review

119 Scopus citations


Glycogen synthase kinase-3 (GSK-3) (EC is a protein kinase highly abundant in brain and involved in signal transduction cascades of multiple cellular processes, particularly neurodevelopment. Two forms of the enzyme, GSK-3α and -3β have been previously identified. We have previously reported reduced GSK-3β protein levels in postmortem frontal cortex of schizophrenic patients. In an attempt to explore whether reduction of GSK-3β levels is brain region specific we examined it in occipital cortex. In order to find out if the reduction in frontal cortex is reflected in altered activity we measured GSK-3 enzymatic activity in this brain region. Western-blot analysis of GSK-3β was carried out in postmortem occipital cortex of 15 schizophrenic, 15 bipolar, and 15 unipolar patients, and 15 normal controls. GSK-3 activity was measured by quantitating the phosphorylation of the specific substrate phospho-CREB in the frontal cortex specimens. GSK-3β levels in occipital cortex did not differ between the four diagnostic groups. GSK-3 activity in the frontal cortex of schizophrenic patients was 45% lower than that of normal controls (0.196±0.082 and 0.357±0.084 pmol/mg protein x min, respectively; Kruskal-Wallis analysis: chi-square=8.27, df=3, p=0.04). The other two diagnostic groups showed no difference from the control group. Our results are consistent with the notion that schizophrenia involves neurodevelopmental pathology.

Original languageEnglish
Pages (from-to)101-105
Number of pages5
JournalSchizophrenia Research
Issue number1-2
StatePublished - 1 Oct 2001


  • Enzyme activity
  • Frontal cortex
  • Glycogen synthase kinase-3
  • Occipital cortex
  • Postmortem brain
  • Protein levels

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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