Family-based association study of 5-HT2A receptor T102C polymorphism and suicidal behavior in Ashkenazi inpatient adolescents

Abstract

Suicidal behavior runs in families and is partially genetically determined. Since greater serotonin 5-HT 2A receptor binding has been reported in postmortem brain and platelets of suicide victims, the 5-HT 2A receptor gene polymorphism T102C became one of the candidate sites in the study of suicide and impulsive-aggressive traits. However, studies that examined the association of this polymorphism with suicidality have contradictory results. This study used a family-based method and one homogenous ethnic group to overcome ethnic stratification in order to test this association. Methods·. Thirty families of inpatient adolescents from Jewish Ashkenazi origin, with a recent suicide attempt, were genotyped. All subjects were interviewed for clinical diagnosis, depressive and impulsive-aggressive traits and demographic data. Allele frequencies were assessed using the Haplotype Relative Risk method for trios. Results: No difference was found in allelic distribution between transmitted and non-transmitted alleles. There was no significant association of genotype with any of the clinical traits Conclusions: These preliminary results suggest that the 5-HT 2A T102C polymorphism is unlikely to be associated with suicidal behavior and related traits in adolescent suicide attempters.

Advances in Research on Adolescent Suicide and a High Priority Agenda for Future Research

“…These findings suggest a potential role of genes involved in processes that may decrease HPA axis sensitivity to feedback or alter cortisol secretion, which is consistent with tentative evidence for associations between genes linked to inflammatory responses and suicidal behaviors in older or mixed-age samples (Clive et al, 2016;Galfalvy et al, 2015;Guintivano et al, 2014). Further, Zalsman et al found associations between MAOA genotypes and STBs among suicidal adolescents presenting at, or admitted to, the hospital (Zalsman et al, 2011), but did not find significant effects for 5-HTR2A (i.e., a serotonergic candidate gene) in another investigation (Zalsman et al, 2005). A recent study found that specific haplotypes within HTR2C and ANKK1-DRD2 genes, which are implicated in serotonergic and dopaminergic pathways, significantly altered risk for suicidal ideation in adolescence depending on individuals' genetic background (Hill, Jones, & Haas, 2020).…”

Genetic Association Studies of Suicidal Behavior: A Review of the Past 10 Years, Progress, Limitations, and Future Directions

“…One possible reason for this is the difficulty of obtaining genetic research consents for minors. Two teams in the world have published several articles, the Zalsman et al ( 34 , 68 , 72 ) and the Brent et al ( 15 ) teams.…”

“…The authors show that there was no significant allelic association of A218C polymorphism with suicide attempt or other phenotypic measures according to the HRR method (chi-square = 0.094; p = 0.76) and the TDT method (chi-square = 0.258; p = 0.61). In the same population, Zalsman et al ( 68 ) tested T102C polymorphism (5-HTR2A gene) without demonstrating any significant association in allelic distribution between transmitted and non-transmitted alleles. Similarly, there was no significant association of genotype with any of the clinical traits.…”

Genetic determinants of aggression and impulsivity in humans

“…However, Prichard et al (2008) failed to observe any significant association between this marker and a range of behaviors including psychosis, agitation, aberrant motor behavior, and depression. No association was found between rs6313 and suicidal behavior in normal subjects (Correa et al 2007), patients with schizophrenia (Ertugrul et al 2004), and suicide attempters (Zalsman et al 2005). The marker G(−1438)A was shown to be associated with increased impulsivity in normal individuals ) and alcoholics (Preuss et al 2001).…”