The 5-HT(2A) receptor gene 102T/C polymorphism is associated with suicidal behavior in depressed patients.
ABSTRACT Several lines of evidence suggest that genetic factors constitute an important determinant of suicidal behavior. A significant association between the 5-HT(2A)-C allele and suicidality has recently been reported. The aim of this study was to investigate whether the proposed association between 5-HT(2A)-102T/C polymorphism and suicidality could be replicated in a larger and independent sample of Spanish patients with major depression. The 102T/C polymorphism of the 5-HT(2A) receptor gene was analyzed in 159 patients with major depression (DSM-IV criteria) and 164 unrelated and healthy controls using a case control design. All individuals were subjects of Spanish origin. Significant differences in allele (chi-square = 4.13, df = 1, P = 0.04) and genotype (chi-square = 6.19, df = 2, P = 0.04) distributions were found between non-suicide attempters and suicide attempters. Moreover, those patients carrying 5-HT(2A)-C allele had more than five times the risk for attempting suicide than noncarriers (OR = 5.50, 95% CI = 1.18-35.20, P = 0.01). Our results replicate the proposed association between 5HT(2A)-C allele and suicidality in major depression. Moreover, no overall associations are detected when patients with major depression and controls are compared for 102T/C frequencies, suggesting that the increased risk for suicidality conferred by 5-HT(2A)-C allele is primarily associated with suicidal behavior and not with the diagnosis of major depression itself.
- SourceAvailable from: Gaël Quesseveur[Show abstract] [Hide abstract]
ABSTRACT: An association between serotonin 2A receptor (5-HT2AR), encoded by HTR2A gene, and major depressive disorder (MDD) has been suggested. Here, we combined preclinical and ecological clinical approaches to explore the impact of impaired 5-HT2AR-mediated transmission on MDD or anxio-depressive-like phenotype in mice. Htr2a knock-out mice (Htr2a-/- ) and wild-type mice were compared for the ability of chronic corticosterone to elicit some anxio-depressive-like phenotype in three behavioral paradigms (elevated plus maze, tail suspension test and splash test). Accordingly, two single nucleotide polymorphisms of the HTR2A gene (rs6314 ie His452Tyr and rs6313 ie 102C/T), which specific allelic variants may decrease 5-HT2AR-mediated transmission (as in Htr2a-/-mice), were studied in a sample of 485 Caucasian patients with MDD. In response to chronic corticosterone exposure, Htr2a-/- mice displayed more pronounced anxiodepressive-like phenotype than wild-type mice, as shown by a significant higher “emotionality score” (p < 0.01). In patients, the C allele of rs6313 was more frequent in depressed patients (p = 0.019) and was also associated with a more severe major depressive episode (p = 0.03). This translational and ecological study involving constitutive Htr2a-/- knock-out mice and related SNPs in depressed patients suggests that a lower neurotransmission at the 5-HT2AR may favor the susceptibility and severity of MDE. It also suggests that specific allelic variants of the rs6313 and rs6314 may reduce 5-HT2AR-mediated transmission.Progress in Neuro-Psychopharmacology and Biological Psychiatry 10/2014; 54:76–82. · 4.03 Impact Factor
- Ekologicheskaya Genetika. 01/2007; 5(4):11-15.
Article: Genetic Determinants of Depression[Show abstract] [Hide abstract]
ABSTRACT: The aim of the studies in this genetic epidemiological thesis was to investigate candidate genes that play a role in the etiology of depression and to obtain new insights about biological pathways that may be involved in this disorder. The introduction of the thesis presents a review of all genetic studies on major depressive disorder (MDD), addressing 393 polymorphisms in 102 genes. Meta-analyses of the twenty-two polymorphisms that had been investigated in at least three studies showed statistically significant associations for six polymorphisms in the following genes: apolipoprotein E (APOE), guanine nucleotidebinding protein (GNB3), methylene-tetrahydrofolate reductase (MTHFR), serotonin transporter (SLC6A4), dopamine transporter (SLC6A3) and the dopamine receptor D4 (DRD4). Next, the thesis describes two candidate gene studies on the association between depression and the angiotensin I converting enzyme insertion/deletion (ACE I/D) and the angiotensino! gen (AGT) M235T polymorphisms. In a large-scale population-based and family-based study, men carrying the AGT M235T TT genotype had more symptoms of depression, but there was no evidence for an association between the ACE gene and depression. Finally, the thesis reports three studies on the co-morbidity of symptoms of depression with socioeconomic status, cardiovascular risk factors and body composition. These studies showed evidence for a common genetic etiology between symptoms of depression with both socioeconomic status and lipid parameters. This thesis shows that genetic research on depression is still in an early stage. More research is necessary both to confirm reported genetic associations and to identify new susceptibility genes. Interesting areas of gene discovery may be found in the overlapping etiological pathways of socioeconomic status and lipid parameters with depression.Social Science & Medicine Part F Medical and Social Ethics 01/2008;