Mood stabilizer treatment increases serotonin type 1A receptor binding in bipolar depression.
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.
1Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, USA.
Allison C
AC
Nugent
Paul J
PJ
Carlson
Earle E
EE
Bain
William
W
Eckelman
Peter
P
Herscovitch
Husseini
H
Manji
Carlos A
CA
Zarate
Wayne C
WC
Drevets
D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D001714:Bipolar Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D059907:Functional Neuroimaging; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018020:Lithium Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011869:Radioligand Assay; D011877:Radionuclide Imaging; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use*; D055815:Young Adult
D018020:Lithium Compounds; D044282:Receptor, Serotonin, 5-HT1A; D014635:Valproic Acid
Positron-emission tomography; bipolar disorder; lithium; serotonin type 1A receptor; valproic acid