Lithium increases platelet serine-9 phosphorylated GSK-3β levels in drug-free bipolar disorder during depressive episodes.

Abstract

BACKGROUND:

Glycogen synthase kinase-3 β (GSK3β) is an intracellular enzyme directly implicated in several neural processes relevant to bipolar disorder (BD) pathophysiology. GSK3β is also an important target for lithium and antidepressants. When phosphorylated at serine-9, GSK3β becomes inactive. Few studies evaluated serine-9 phosphorylated GSK3β (phospho-GSK3β) levels in BD subjects in vivo and no study has assessed it specifically in bipolar depression. Also, the effect of lithium monotherapy on GSK3β has never been studied in humans.

METHODS:

In 27 patients with bipolar depression, total GSK3β and phospho-GSK3β were assessed in platelets by enzyme immunometric assay. Subjects were evaluated before and after 6 weeks of lithium treatment at therapeutic levels. Healthy subjects (n = 22) were used as a control group.

RESULTS:

No differences in phospho-GSK3β or total GSK3β were observed when comparing drug-free BD subjects in depression and healthy controls. Baseline HAM-D scores were not correlated with phospho-GSK3β and total GSK3β levels. From baseline to endpoint, lithium treatment inactivated GSK3β by significantly increasing phospho-GSK3β levels (p = 0.010). Clinical improvement (baseline HAM-D - endpoint HAM-D) negatively correlated with the increase in phospho-GSK3β (p = 0.03).

CONCLUSION:

The present results show that lithium inactivates platelet GSK3β in BD during mood episodes. No direct association with pathophysiology of BD was observed. Further studies are needed to clarify the role of GSK3β as a key biomarker in BD and its association with treatment response as well as the relevance of GSK3β in other neuropsychiatric disorders and as a new therapeutic target per se.

• Authors: Rafael T de Sousa, Marcus V Zanetti, Leda L Talib, Mauricio H Serpa, Tiffany M Chaim, Andre F Carvalho, Andre R Brunoni, Geraldo F Busatto, Wagner F Gattaz, Rodrigo Machado-Vieira
• Journal: Journal of psychiatric research (J Psychiatr Res) Vol. 62 Pg. 78-83 (Mar 2015) ISSN: 1879-1379 [Electronic] England
• PMID: 25691093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Antidepressive Agents
• Lithium Carbonate
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Glycogen Synthase Kinase 3

Topics

• Adult
• Antidepressive Agents (therapeutic use)
• Bipolar Disorder (blood, drug therapy)
• Blood Platelets (drug effects)
• Female
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• Humans
• Lithium Carbonate (therapeutic use)
• Male
• Phosphorylation
• Psychiatric Status Rating Scales
• Statistics as Topic
• Young Adult