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.
Specifically, we investigated two serotonin-related genes including three substitutions connected to human emotional states such as despondency and depression: the tryptophan hydroxylase (TPH) gene (A779C and A218C in the intron) and the serotonin1A (5-HT1A) receptor gene (Pro 16Leu in the cording region).
We studied in the current work the disturbances in the FGFR1-5-HT1A heterocomplexes in a genetic rat model of depression, the Flinders sensitive line (FSL) rats of Sprague-Dawley (SD) origin, by means of neurochemical, neurophysiological and behavioral techniques.
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.
The authors review evidence that altered transcription of the 5-HT1A receptor can affect the serotonin system and limbic and cortical areas, leading to predisposition to depression.
The NET and 5-HT1A polymorphisms appear to have similar effects on hippocampal volume in patients and controls while the 5-HTTLPR polymorphism differentially affects hippocampal volume in the presence of depression.
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.
Patients carrying the HTR1A CC genotype and the COMT Val/Val genotype (HR = 3.25) had a higher risk of depression than patients with the G allele (HTR1A) and the Val/Val genotype.
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.
We investigated the possible association between depression and anxiety scores and SNPs within the HTR1A and HTR1B genes in a population sample (n=1387).
Subgroups of 43 patients with LMD, 96 with HTR1A-G allele, and 12 with both LMD and HTR1A-G homozigosity scored significantly higher to depression compared to the remaining patients during antiviral therapy.
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 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.
Six functional SNPs in genes related to the serotonergic system were examined: serotonin transporter (5HTTLPR including rs25531), 5HT1A C-(1019)G and 5HT2A T-(102)C, methylene tetrahydrofolate reductase (MTHFR) C-(677)T, brain-derived neurotrophic factor (BDNF) val66met and tryptophan hydroxylase-2 (TPH2) G-(703)T. Regression analyses were performed using the six SNPs as independent variables: Model 1 with response (percentage Hamilton Depression (HAMD) change from baseline to endpoint) as the dependent variable and Model 2 with adverse event index as the dependent variable (Bonferroni corrected p-value < 0.025).
The current study aimed to investigate the interaction between the serotonin 1A receptor gene (HTR1A) C-1019G polymorphism and recent negative life stressors on depression in a Korean community sample.
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.
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).
Correction: Epistasis of HTR1A and BDNF risk genes alters cortical 5-HT1A receptor binding: PET results link genotype to molecular phenotype in depression.