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Lithium increases platelet serine-9 phosphorylated GSK-3β levels in drug-free bipolar disorder during depressive episodes
- Source :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP
- Publication Year :
- 2014
-
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 .
- Subjects :
- Adult
Blood Platelets
Male
medicine.medical_specialty
Bipolar Disorder
Lithium (medication)
Statistics as Topic
Young Mania Rating Scale
LÍTIO (EFEITOS ADVERSOS)
Glycogen Synthase Kinase 3
Young Adult
Lithium Carbonate
Internal medicine
medicine
Humans
Platelet
Bipolar disorder
Phosphorylation
Glycogen synthase
Biological Psychiatry
Psychiatric Status Rating Scales
Glycogen Synthase Kinase 3 beta
biology
medicine.disease
Pathophysiology
Antidepressive Agents
Psychiatry and Mental health
Mood
Endocrinology
biology.protein
Biomarker (medicine)
Female
Psychology
medicine.drug
Subjects
Details
- ISSN :
- 18791379
- Volume :
- 62
- Database :
- OpenAIRE
- Journal :
- Journal of psychiatric research
- Accession number :
- edsair.doi.dedup.....02a77b94d11ad554b1da5bcafb2a5a8f