Mood stabilizer treatment increases serotonin type 1A receptor binding in bipolar depression. (October 2013)

• Record Type: Journal Article
• Authors: Nugent, Allison C; Carlson, Paul J; Bain, Earle E; Eckelman, William; Herscovitch, Peter; Manji, Husseini; Zarate, Carlos A; Drevets, Wayne C
• Is Part Of: Journal of psychopharmacology. Volume 27:Number 10(2013)
• Page Start: 894
• Page End: 902
• Publication Date: 2013-10
• Subjects: Positron-emission tomography -- lithium -- valproic acid -- serotonin type 1A receptor -- bipolar disorder; Psychopharmacology -- Periodicals; 615.78
• DOI: 10.1177/0269881113499204
• Languages: English
• ISSNs: 0269-8811

Abstract

Abnormal serotonin type 1A (5-HT1A ) receptor function and binding have been implicated in the pathophysiology of mood disorders. Preclinical studies have consistently shown that stress decreases the gene expression of 5-HT1A receptors in experimental animals, and that the associated increase in hormone secretion plays a crucial role in mediating this effect. Chronic administration of the mood stabilizers lithium and divalproex (valproate semisodium) reduces glucocorticoid signaling and function in the hippocampus. Lithium has further been shown to enhance 5-HT1A receptor function. To assess whether these effects translate to human subject with bipolar disorder (BD), positron emission tomography (PET) and [18F]trans-4-fluoro-N-(2-[4-(2-methoxyphenyl) piperazino]-ethyl)-N-(2-pyridyl) cyclohexanecarboxamide ([ 18 F]FCWAY) were used to acquire PET images of 5-HT1A receptor binding in 10 subjects with BD, before and after treatment with lithium or divalproex. Mean 5-HT1A binding potential (BPP ) significantly increased following mood stabilizer treatment, most prominently in the mesiotemporal cortex (hippocampus plus amygdala). When mood state was also controlled for, treatment was associated with increases in BPP in widespread cortical areas. These preliminary findings are consistent with the hypothesis that these mood stabilizers enhance 5-HT1A receptor expression in BD, which may underscore an important component of these agents' mechanism of action.