Citation

Karege F, Perroud N, Burkhardt S, Schwald M, Ballmann E, La Harpe R, Malafosse A. Biol. Psychiatry 2007; 61(2): 240-245.

Affiliation

Department of Psychiatry, Geneva University Hospitals, Chêne-Bourg, Geneva, Switzerland. felicien.karege@biolo.unige.ch

Comment In:

Biol Psychiatry 2007;61(2):139-41

Copyright

(Copyright © 2007, Elsevier Publishing)

DOI

10.1016/j.biopsych.2006.04.036

PMID

16876135

Abstract

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.

Language: en