Abstract
BackgroundSerotonergic neurotransmission has been implicated in suicidal behavior. Association between suicidal completers and a regulatory C(-1019)G polymorphism (rs6295) in the serotonin 1A receptor (HTR1A) gene was previously reported, whereas a following study showed no association in a sample of suicide attempters.MethodsThe involvement of the implicated G-allele of the 5-HTR1A C(-1019)G polymorphism (rs6295) was analyzed with the transmission disequilibrium test (TDT) in a sample of 272 suicide attempter families.ResultsNo overtransmission of the G-allele was found in the entire sample of suicide attempters (p = 0.1460; n = 272 trios). However, a strong trend for overtransmission of the G-allele was observed in a sub-sample selected for a high level of previous traumatic and/or stressful life events prior to the suicide attempt (p = 0.0630, two-tail; n = 94 trios).ConclusionThe current results show that variation at the rs6295 polymorphism of the HTR1A gene is not associated with suicide attempts generally. However, the results indicate a possible role of the G-allele in suicidal behavior in connection with high exposure to traumatic and/or stressful life events, which is in need of future investigation.
Highlights
Serotonergic neurotransmission has been implicated in suicidal behavior
In a series of experiments, it was shown that the part of the HTR1A gene promoter that contains single nucleotide polymorphism (SNP) rs6295 binds to the transcription factor named nuclear deformed epidermal autoregulatory factor DEAF-1/suppressin (NUDR), that this factor represses transcription of HTR1A and that this inhibitory action was impaired for the G-allele, the same allele that was associated with suicide and major depression [6]
The discrepancies between these studies may reflect a problem of population stratification, which can be overcome by using the transmission disequilibrium test (TDT) [9]
Summary
Serotonergic neurotransmission has been implicated in suicidal behavior. Association between suicidal completers and a regulatory C(-1019)G polymorphism (rs6295) in the serotonin 1A receptor (HTR1A) gene was previously reported, whereas a following study showed no association in a sample of suicide attempters. The implication is that failed inhibition by NUDR at the G-allele leads to higher expression of HTR1A This could enhance the negative feedback inhibition of serotonergic raphe neurons exerted by HTR1A autoreceptors and lead to a lower serotonergic neurotransmission, which is consistent with the observation of low serotonin-levels in depression and suicide. The most recent report showed no association of the G-allele to alcoholism and suicide attempts generally, but association to Babors type B alcoholism and number of suicide attempts in history [8] The discrepancies between these studies may reflect a problem of population stratification, which can be overcome by using the transmission disequilibrium test (TDT) [9]
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