Reduced post-synaptic serotonin type 1A receptor binding in bipolar depression

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• 作者：Allison C. Nugent ; Earle E. Bain ; Paul J. Carlson ; Alex ; er Neumeister ; Omer Bonne ; Richard E. Carson ; William Eckelman ; Peter Herscovitch ; Carlos A. Zarate Jr. ; Dennis S. Charney ; Wayne C. Drevets
• 关键词：5-HT1A receptor ; Positron-emission tomography ; Bipolar disorder ; (18F)FCWAY
• 刊名：European Neuropsychopharmacology
• 出版年：2013
• 出版时间：August, 2013
• 年：2013
• 卷：23
• 期：8
• 页码：822-829
• 全文大小：820 K

文摘

Multiple lines of evidence suggest that serotonin type 1A (5-HT_1A) receptor dysfunction is involved in the pathophysiology of mood disorders, and that alterations in 5-HT_1A receptor function play a role in the mechanisms of antidepressant and mood stabilizer treatment. The literature is in disagreement, however, as to whether 5-HT_1A receptor binding abnormalities exist in bipolar disorder (BD). We acquired PET images of 5-HT_1A receptor binding in 26 unmedicated BD subjects and 37 healthy controls using [¹⁸F]FCWAY, a highly selective 5-HT_1A receptor radio-ligand. The mean 5-HT_1A receptor binding potential (BP_P) was significantly lower in BD subjects compared to controls in cortical regions where 5-HT_1A receptors are expressed post-synaptically, most prominently in the mesiotemporal cortex. Post-hoc assessments involving other receptor specific binding parameters suggested that this difference particularly affected the females with BD. The mean BP_P did not differ between groups in the raphe nucleus, however, where 5-HT_1A receptors are predominantly expressed pre-synaptically. Across subjects the BP_P in the mesiotemporal cortex was inversely correlated with trough plasma cortisol levels, consistent with preclinical literature indicating that hippocampal 5-HT_1A receptor expression is inhibited by glucocorticoid receptor stimulation. These findings suggest that 5-HT_1A receptor binding is abnormally reduced in BD, and this abnormality may particularly involve the postsynaptic 5-HT_1A receptor system of individuals with a tendency toward cortisol hypersecretion.