Alteration in kinase activity but not in protein levels of protein kinase B and glycogen synthase kinase-3beta in ventral prefrontal cortex of depressed suicide victims

Biol Psychiatry. 2007 Jan 15;61(2):240-5. doi: 10.1016/j.biopsych.2006.04.036. Epub 2006 Jul 28.


Background: Past studies in the neurobiology of suicide have reported alterations in serotonin and downstream effectors, such as Akt/protein kinase B. In this study, we aimed to examine possible abnormality in the Akt/glycogen synthase kinase-3beta (GSK-3beta) axis of depressed suicide victims' brains.

Methods: Twenty suicide victims and 20 drug-free non-suicide subjects were included for a postmortem study. The ventral prefrontal cortex area (BA'11) was used, and antemortem diagnoses of major depression disorder (MDD) (DSM-IV) were made from Institution's records. The protein levels of GSK-3alpha/beta and Akt-1 were assayed with the Western blot method, and the kinase activity of Akt and GSK-3alpha/beta were determined by phosphorylation of specific substrates.

Results: There was no change either in GSK-3alpha/beta and Akt-1 protein levels or in lithium-inhibitable total GSK-3alpha/beta enzyme activity of the ventral prefrontal cortex. The enzyme activity of Akt decreased significantly [analysis of variance (ANOVA): F(3,36)=5.372; p= .003], whereas GSK-3beta activity increased significantly [ANOVA: F(3,36)=8.567; p= .002] in depressed suicide victims and non-suicide subjects but not in non-depressed suicide victims.

Conclusions: This study indicated that the activity rather than the protein levels of Akt and GSK-3beta was altered. The alteration was associated with MDD rather than with suicide per se.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cause of Death
  • Depressive Disorder, Major / pathology*
  • Female
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Immunoblotting
  • Male
  • Middle Aged
  • Prefrontal Cortex / pathology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Reference Values
  • Suicide / psychology*


  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3
  • glycogen synthase kinase 3 alpha