Long-term sertraline treatment increases expression and decreases phosphorylation of glycogen synthase kinase-3B in platelets of patients with late-life major depression

• Published in: Journal of psychiatric research Vol. 46; no. 8; pp. 1053 - 1058
• Main Authors: Joaquim, Helena P.G, Talib, Leda L, Forlenza, Orestes V, Diniz, Breno S, Gattaz, Wagner F
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.08.2012; Elsevier
• Subjects: Adult and adolescent clinical studies; Aged; Aged, 80 and over; Analysis of Variance; Antidepressant drugs; Antidepressant treatment; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Biological and medical sciences; Biomarkers; Blood Platelets - drug effects; Blood Platelets - metabolism; Depression; Depressive Disorder, Major - blood; Depressive Disorder, Major - drug therapy; Depressive personality disorders; Female; Geriatrics; Glycogen Synthase Kinase 3 - blood; Glycogen Synthase Kinase 3 beta; Humans; Immunoenzyme Techniques; Induced; Longitudinal Studies; Male; Medical sciences; Middle Aged; Mood disorders; Neuropharmacology; Pharmacology. Drug treatments; Phosphorylation - drug effects; Platelets; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Regulation; Residence Characteristics; Sertraline; Sertraline - pharmacology; Sertraline - therapeutic use; Biomarkers; Antidepressant treatment; Platelets; Glycogen synthase kinase 3-beta; Phosphorylation; Psychotropic; Glycogen synthase kinase-3; Biological marker; Synthase; Reuptake inhibitor; Selective serotonin reuptake inhibitor; Antidepressant agent; Mood disorder; Human; Serotonin; Enzyme; Glycogen; Transferases; Depression; Long term; Sertraline; Naphthylamine derivatives; Platelet; Treatment; Kinase; Geriatric depression; Neurotransmitter; Elderly
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/j.jpsychires.2012.04.020

Abstract Background Abnormal regulation of glycogen synthase kinase 3-beta (GSK3B) activity has been implicated in the pathophysiology of mood disorders. Many pharmacological agents, including antidepressants, can modulate GSK3B. The aim of the present study was to investigate the effect of short-and long-term sertraline treatment on the expression and phosphorylation of GSK3B in platelets of patients with late-life major depression. Methods Thirty-nine unmedicated elderly adults with major depressive disorder (MDD) were initially included in this study. The comparison group comprised 18 age-matched, healthy individuals. The expression of total and Ser-9 phosphorylated GSK3B (pGSK3B) was determined by Enzyme Immunometric Assay (EIA) in platelets of patients and controls at baseline, and after 3 and 12 months of sertraline treatments for patients only. During this period, patients were continuously treated with therapeutic doses of sertraline. GSK3B activity was indirectly estimated by calculating the proportion of inactive (phosphorylated) forms (pGSK3B) in relation to the total expression of the enzyme (i.e., GSK3B ratio). Results Depressed patients had significantly higher levels of pGSK3B as compared to controls ( p  < 0.001). Within the MDD group, after 3 months of sertraline treatment no significant changes were observed in GSK3B expression and phosphorylation state, as compared to baseline levels. However, after 12 months of treatment we found a significant increase in the expression of total GSK3B ( p  = 0.05), in the absence of any significant changes in pGSK3B ( p  = 0.12), leading to a significant reduction in GSK3B ratio ( p  = 0.001). Conclusions Our findings indicate that GSK3B expression was upregulated by the continuous treatment with sertraline, along with an increment in the proportion of active forms of the enzyme. This is compatible with an increase in overall GSK3B activity, which may have been induced by the long-term treatment of late-life depression with sertraline.