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

Author(s)

de Sousa, Rafael T. ^[1] ; Zanetti, Marcus V. ^{[2, 1, 3]} ; Talib, Leda L. ^[1] ; Serpa, Mauricio H. ^[3] ; Chaim, Tiffany M. ^[3] ; Carvalho, Andre F. ^{[4, 5]} ; Brunoni, Andre R. ^[1] ; Busatto, Geraldo F. ^{[2, 3]} ; Gattaz, Wagner E. ^{[2, 1]} ; Machado-Vieira, Rodrigo ^{[2, 6, 1]}

Affiliation

^[1] Univ Sao Paulo, Lab Neurosci, Inst & Dept Psychiat, LIM 27, BR-05508 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-05508 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Lab Psychiat Neuroimaging, LIM 21, Dept & Inst Psychiat, BR-05508 Sao Paulo - Brazil

^[4] Univ Fed Ceara, Translat Psychiat Res Grp, Fac Med, Fortaleza, Ceara - Brazil

^[5] Univ Fed Ceara, Dept Clin Med, Fac Med, Fortaleza, Ceara - Brazil

^[6] NIMH, ETPB, NIH, Bethesda, MD 20892 - USA

• Document type: Journal article
• Source: JOURNAL OF PSYCHIATRIC RESEARCH; v. 62, p. 78-83, MAR 2015.
• Web of Science Citations: 20

Abstract

Background: Glycogen synthase kinase-3 beta (GSK3 beta) is an intracellular enzyme directly implicated in several neural processes relevant to bipolar disorder (BD) pathophysiology. GSK3 beta is also an important target for lithium and antidepressants. When phosphorylated at serine-9, GSK3 beta becomes inactive. Few studies evaluated serine-9 phosphorylated GSK3 beta(phospho-GSK3 beta) levels in BD subjects in vivo and no study has assessed it specifically in bipolar depression. Also, the effect of lithium monotherapy on GSK3 beta has never been studied in humans. Methods: In 27 patients with bipolar depression, total GSK3 beta and phospho-GSK3 beta 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-GSK3 beta or total GSK3 beta were observed when comparing drug-free BD subjects in depression and healthy controls. Baseline HAM-D scores were not correlated with phospho GSK3 beta and total GSK3 beta levels. From baseline to endpoint, lithium treatment inactivated GSK3 beta by significantly increasing phospho-GSK3 beta levels (p = 0.010). Clinical improvement (baseline HAM-D endpoint HAM-D) negatively correlated with the increase in phospho-GSK3 beta (p = 0.03). Conclusion: The present results show that lithium inactivates platelet GSK3 beta in BD during mood episodes. No direct association with pathophysiology of BD was observed. Further studies are needed to clarify the role of GSK3 beta as a key biomarker in BD and its association with treatment response as well as the relevance of GSK3 beta in other neuropsychiatric disorders and as a new therapeutic target per se. Published by Elsevier Ltd. (AU)

• FAPESP's process: 09/14891-9 - Longitudinal study on the neuroprotective and neurotrophic effects of lithium in bipolar disorder: identification of cellular and molecular targets clinically relevant
• Grantee: Rodrigo Machado-Vieira
• Support Opportunities: Research Grants - Young Investigators Grants