HTR2C and HTR1A gene variants in German and Italian suicide attempters and completers

Abstract

The serotonin 2C (HTR2C) and 1A (HTR1A) receptors have been involved in suicide-related behaviors. We studied gene variants of both receptors in suicide attempters and completers. The sample was composed of 167 German suicide attempters (affective spectrum n = 107, schizophrenia spectrum n = 35, borderline personality disorder n = 25), 92 Caucasian individuals who committed suicide, 312 German healthy subjects, 152 Italian suicide attempters (major depression n = 68 and bipolar disorder n = 84), and 131 Italian healthy volunteers. HTR2C (SNP: rs547536, rs2192372, rs6318, rs2428707, rs4272555, rs1801412) and HTR1A (SNP: rs1423691, rs878567, and rs6295) variants were analyzed in the German sample. HTR2C rs6318 and HTR1A rs6295 were analyzed in the Italian sample. Haplotype analysis in relation to suicidal behaviors did not reveal any significant association. Single markers and haplotypes were not or only marginally associated with other related features, such as violence of suicide attempt, family history for suicide attempt or State-Trait Anger Expression Inventory (STAXI) and Questionnaire for Measuring Factors of Aggression (FAF) scores. In conclusion, our study does not support the notion that HTR2C and HTR1A gene variants are major contributors to suicide-, anger-, or aggression-related behaviors in our sample.

Escitalopram Response in Panic Disorder is Not Associated with Three 5-HT1A Receptor Gene Polymorphisms (Rs6295, Rs10042486, or Rs1364043) in Chinese-Han Patients

“…A brain imaging study also found that the G allele and 5-HT1A receptor binding increases in both the raphe nuclei and other brain regions [19]. Therefore, this could cause a greater extent of desensitization of 5-HT1A auto receptors, reduce raphe firing, decrease serotonin release, and confer resistance to SSRIs [20,21]. In contrast, in cells expressing 5-HT1A post synoptically, Deaf-1 activity is opposed in presynaptic versus postsynaptic neuronal cells.…”

“…In contrast, in cells expressing 5-HT1A post synoptically, Deaf-1 activity is opposed in presynaptic versus postsynaptic neuronal cells. Thus, Deaf-1 activates 5-HT1A transcription by binding to the C allele but not the G allele [20,21]. Therefore, the G-1019 allele might reduce Deaf-1-enhanced postsynaptic 5-HT1A transcription as well as enhance resistance to antidepressant-induced increases in 5-HT [15,16].…”

Genes, the serotonergic system and suicidal behavior

“…Por lo que se ha establecido la asociación del alelo s de este polimorfismo con desordenes cono la ansiedad, depresión y conducta suicida (Lesch et al, 1996;Mann et al, 2000;Pungercic et al, 2006). Un reciente Meta-análisis que analiza a 44 estudios reporto que portadores del alelo corto de este polimorfismo presentan mayor riesgo de conducta suicida (Serretti et al, 2007).…”

“…Variaciones genéticas en el receptor de serotonina 5-HT2A se asocia con la conducta suicida. La mayoría de los estudios que analizan la posible asociación del polimorfismo C102T y la conducta suicida observan un exceso del genotipo C/C en los pacientes con intentos suicidas (Nishiguchi et al, 2002;Ohtani, Shindo, & Yoshioka, 2004;Serretti et al, 2007). Sin embargo los resultados son inconsistentes (Hung et al, 2011;Murphy et al, 2011;Preuss, Koller, Bahlmann, Soyka, & Bondy, 2000).…”

“…Cuando se estudia en relación a la conducta suicida los resultados son inconsistentes. De la misma manera los resultados son controversiales cuando se estudia el polimorfismo C129T (Courtet et al, 2011;Murphy et al, 2011;Okamura et al, 2005;Serretti et al, 2007).…”