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Increased 5-HT1A receptor binding in the brain of depressed patients Serotonin 1A (5-HT1A) receptors are involved in the pathophysiology of major depressive disorder (MDD) and in the mechanism of action of selective serotonin reuptake inhibitors (SSRIs). Chronic, but not acute, exposure to SSRIs desensitizes somatodendritic 5-HT1A autoreceptors in the raphe nuclei and down-regulates the serotonin transporter (5 -HTT), which could explain the lag in clinical treatment response. The C(-1019)G polymorphism of the promoter region of the 5-HT1A gene has been shown to be associated with depression. The presence of the C(-1019) allele results in increased expression of the 5-HT1A protein in the raphe nuclei. Higher 5-HT1A receptor binding in postmortem brain of depressed male suicides has been found in the raphe nuclei. Depressed subjects were scanned to quantify 5-HT1A binding, and to explore the long-term effects of antidepressant exposure and the function of the C(-1019)G polymorphism. Twenty eight subjects with MDD and 43 control subjects were genotyped for the C(-1019)G polymorphism using polymerase chain reaction and 5-HT1A binding potential was determined by positron emission tomography using [carbonyl-C-11]-WAY-100635. There was no difference in binding potential between controls and MDD subjects. However, MDD subjects who were medication naive had higher binding potential across all regions of interest compared to MDD subjects who had been exposed to antidepressants and controls. A higher expression of GG (-1019) genotype was more common in MDD and correlated with higher 5-HT1A binding potential. The increased 5-HT1A autoreceptor binding potential found in antidepressant naive depressed subjects compared to controls and to previously treated depressed subjects may be due to greater gene expression. This may result in less serotonin neuron firing and reduced terminal 5-HT release, and finally in 5-HT hypofunction consistent with the indoleamine hypothesis of major depression. Parsey RV, Oquendo MA, Ogden RT, Olvet DM, Simpson N, Huang YY, Van Heertum RL, Arango V, Mann JJ. Altered serotonin 1A binding in major depression: a [carbonyl-C-11]WAY100635 positron emission tomography study. Biol Psychiatry 2006, 59:106-113. Disclaimer Site conceived and produced by NeuroBiz Consulting & Communications Copyright © Depression-WebWorld Ltd UK, 2006