Association between HTR1B alleles and suicidal ideation in individuals with major depressive disorder

Serotonin receptors, also known as 5-hydroxytryptamine receptors (HTRs), play a role in individuals' vulnerability to major depressive disorders (MDDs) and/or suicide attempts. In the first part of the study, we recruited 789 Taiwanese participants, which included 285 MDD patients, 191 MDD patients with a history of suicide attempts (MS), and 313 controls. The three groups were genotyped to identify HTR single nucleotide polymorphisms (SNPs) and we analyzed the correlations among the three groups. In the second part of the study, which involved a functional test of HTR1B allelic and haplotype variants, another 113 MDD patients were recruited. The rs6298-T allele was more frequent in the MS group than in the control group. The rs1923885-T allele occurred more frequently in the MS group than in the MDD group. Carriers of haplotype GT were estimated to have a 1.774-fold higher risk of suicide attempts. Younger age, alleles rs6296-C, rs6298-T and rs1923885-C, and haplotype CT were associated with a greater risk of MDD. Haplotypes GC and GT were directly associated with a lower risk of suicidal ideation. Haplotypes GC and GT also associated with higher levels of HTR1B mRNA, and haplotype GC was associated with extraversion, which caused a lower risk of suicidal ideation. The rs6296-C allele have directly and indirectly influenced a greater risk of suicidal ideation, which mediated by its negative effect on extraversion. Haplotype GT can be used to identify patients with a higher risk of suicide attempts. The rs6296-C allele lowered the level of HTR1B mRNA, causing individuals with MDD to display more hostility and aggressive behavior, which may lead to suicidal ideation.