A functional promoter polymorphism in the serotonin receptor 1A (5-HT1A) gene has been found to be associated with major depression as well as anxiety- and depression-related personality traits.
After controlling for sociodemographic and disease-related factors, alexithymia and HTR1A-G polymorphism, both separately (20-22%) and jointly (14-16%), significantly and independently predicted the development of IFN-induced depression.
Alterations in 5-HT1A receptor levels are implicated in mood disorders, and a functional C(-1019)G 5-HT1A promoter polymorphism has been associated with depression, suicide, and panic disorder.
AN have higher 5-HT(1A) than controls and AE suggesting a model of depression characterized by an over expression of autoinhibitory somatodendritic 5-HT(1A) receptors, perhaps due to the higher expressing G allele, that may result in reduced terminal field 5-HT release.
Based on animal models, an integrated model for opposing roles of pre- and post-synaptic 5-HT(1A) receptors in anxiety and depression phenotypes and response to antidepressants is proposed.
Behavioral and molecular biological studies have demonstrated that the differences of 5-HT1A receptor regulation was connected with depression and the responses to antidepressants.
Consequently, VN2222 is a new compound with a dual effect on the serotonergic system, as 5-HT uptake blocker and 5-HT1A receptor partial agonist, and with a remarkable activity in an animal model of depression with high predictive validity.
Correction: Epistasis of HTR1A and BDNF risk genes alters cortical 5-HT1A receptor binding: PET results link genotype to molecular phenotype in depression.
Disturbances in the 5-HT1A⁻FGFR1 heteroreceptor complexes in the raphe-hippocampal 5-HT system were found in a genetic rat model of depression (Flinders sensitive line (FSL) rats).
Effects of gene polymorphisms on clinical improvement were analyzed with an analysis of variance with each gene (SERTPR, 5-HT(1A) , and COMT) as factors and the Hamilton Rating Scale for Depression variation from baseline to the end of the treatment as a dependent variable.
Gene-gene interaction studies suggest that the 5-HT1A receptor G(-1019) allele is a risk allele which could be used as a marker for depression and related mood disorders.
Human studies implicate a polymorphism in the promoter of the serotonin-1A (5-HT(1A)) receptor gene in increased susceptibility to depression and decreased treatment response.
In conclusion, our results favor the hypothesis that monoaminergic neurotransmission in general and the F528C NET and R219L5-HT(1A) receptor variants in particular are involved in the pathogenesis of depression.
In humans, the G variant of the C(-1019)G 5-HT1A receptor promoter gene polymorphism (rs6295) has been associated with higher expression of 5-HT1A receptors, increased depression, and lower stress preceding completed suicide.
In our study, the HTR1A C(-1019)G polymorphism was found to be associated to the frequent clinical presentation of comorbid MD and GAD, suggesting a common genetic background for mixed depression and anxiety states.
In this review, we examine the function of 5-HT(1A) receptor subpopulations and re-interpret our understanding of their role in mental illness in light of new data, separating both spatial (autoreceptor versus heteroreceptor) and the temporal (developmental versus adult) roles of the endogenous 5-HT(1A) receptors, emphasizing their distinct actions in mediating anxiety and depression-like behaviors.
It is proposed that the demonstrated 5-HT1A-5-HT2A isoreceptor complexes may play a role in depression through integration of 5-HT recognition, signaling and trafficking in the plasma membrane in two major 5-HT receptor subtypes known to be involved in depression.
Our findings suggest an impact of allelic variation in 5-HT(1A) receptor expression on the development of interferon alfa-induced depression during antiviral treatment of chronic hepatitis C. Prediction models of interferon-induced depressive symptoms based on HTR1A variation offer a perspective for an antidepressant selective serotonin reuptake inhibitor prophylaxis in patients genetically at risk for interferon-induced depression.