Alteration in Kinase Activity But Not in Protein Levels of Protein Kinase B and Glycogen Synthase Kinase-3β in Ventral Prefrontal Cortex of Depressed Suicide Victims

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-3β (GSK-3β) 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-3α/β and Akt-1 were assayed with the Western blot method, and the kinase activity of Akt and GSK-3α/β were determined by phosphorylation of specific substrates. Results: There was no change either in GSK-3α/β and Akt-1 protein levels or in lithium-inhibitable total GSK-3α/β 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-3β 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-3β was altered. The alteration was associated with MDD rather than with suicide per se.