Assessment of human serotonin 1A receptor polymorphisms and SSRI responsiveness

Background: Depression is thought to involve, in part, dysregulation of serotonergic neurotransmission. In depressed individuals, the number of serotonin receptors, including the 5-hydroxytryptamine (serotonin)-1A (5-HT1A) autoreceptors, are increased. Clinical improvement with selective serotonin reuptake inhibitors (SSRls) is not usually observed until several weeks after treatment initiation. This delay may be due to the time it takes for the autoreceptors to downregulate. Roughly one-third of patients with depression do not respond to an initial trial of antidepressant medication treatment, possibly as a result of structural variations in the 5-HT1A receptor. Aims: This study was designed to determine the allelic frequency of seven 5-HT1A receptor polymorphisms in a depressed versus a nondepressed population, and in SSRI responders versus nonresponders. All the polymorphisms studied are single nucleotide polymorphisms (SNPs) in the HTR1A gene, which encodes 5-HT1A. Seven prevalent SNPs were included in the analysis. Results: The study showed no relationship between any of the HTR1A polymorphisms and SSRI responders versus nonresponders. Conclusion: While the study has several limitations, the results are consistent with a growing body of literature that suggests that the pharmacogenetics of depression (an inherently complex disorder) may turn out to be multifactorial, and may include the HTR1A gene in concert with other serotonin-related genes.