The impact of serotonin receptor 1A and 2A gene polymorphisms and interactions on suicide attempt and suicide risk in depressed patients with insufficient response to treatment – a European multicentre study

Abstract

So far, associations between serotonergic neurotransmission pathways and suicidality have been reported. The aim of our study was to investigate the role of genetic polymorphisms and gene-gene interactions of the 5-HTR1A and the 5-HTR2A gene on suicide risk and/or a personal history of suicide attempts. A total of 374 major depressive disorder patients, adequately treated with antidepressants for at least 4 weeks, were collected in the context of a European multicentre study on treatment-resistant depression. We assessed suicidality using the Mini International Neuropsychiatric Interview and the Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D ≤ 17 and remission as HAM-D ≤ 7 after 4 weeks of adequate antidepressant treatment. The 5-HTR1A rs6295 (C-1019G) single nucleotide polymorphism (SNP) and the 5-HTR2A rs7997012, rs6313, rs643627 and rs17288723 SNPs were selected for genotyping. Using logistic regression analyses, no association (P<0.05) could be found between any SNP and neither suicide risk nor personal history of suicide attempts. Interactions between 5HTR1A rs6295 and 5HTR2A rs6313 in suicide risk, and 5HTR1A rs6295 and 5HTR2A rs643627 in a personal history of suicide attempts have been reported (P=0.027 and 0.036, respectively); however, the results did not survive multiple testing correction. In conclusion, our study shows no association between 5HTR1A or 5HTR2A gene polymorphisms and both current suicide risk and personal history of suicide attempts. In addition, epistatic effects of 5HTR1A and 5HTR2A genes on suicidal behaviour were not significant, although sample size limitations do not allow definitive conclusions.

Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigm

“…61 Similarly, other studies did not find an association between rs6295/ stress and depression. 152 An association with suicide or suicide attempt has been seen for rs6295 alone in some but not all studies, 61,153,154 and in other studies the rs6295 genotype has been associated with suicide attempt or suicide only in people with previous trauma. 155,156 The rs6295 HTR1A gene polymorphism is one of several SNPs that has been shown to interact with stress exposure in depression susceptibility, 67 each study showing a stress-associated increase in depression frequency for risk alleles.…”

The serotonin transporter and the activity regulated cytoskeleton‐associated protein genes in antidepressant response and resistance: 5‐HTTLPR and other variants

“…5-HT pathways are also involved in the regulation of dopamine and norepinephrine networks (Cubala & Landowski, 2006;Daszuta, Ban, Soumier, Hery, & Mocaer, 2005). Serotonergic genes have been widely studied also as modulators of TRD (Coplan, Gopinath, Abdallah, & Berry, 2014;Hofer et al, 2016). The serotonin transporter gene (SLC6A4) has been the subject of particular interest, because the coded protein is the primary target of selective serotonin reuptake inhibitors.…”

Pharmacogenetics of citalopram-related side effects in children with depression and/or anxiety disorders

“…In adults, it was shown that the HTR2A CC genotype (rs6313) was strongly associated with discontinuation due to intolerance in patients treated with paroxetine (Murphy et al 2003). Recently, Hofer et al investigated polymorphisms in the 5-HTR1A and 5-HTR2A genes, including rs6313, and found no association between them and suicide risk (Hofer et al 2016).…”