Impact of Serotonin Pathway Gene Polymorphisms and Serotonin Levels in Suicidal Behaviour

Abstract

<b><i>Objective:</i></b> Suicide is a significant public health issue and a major cause of death in all ages worldwide. Previous studies have shown the involvement of genetics in suicidal behaviour. This study aimed to assess the role of the genetic variants of the serotonin transporter genes (<i>5HTTLPR</i>, <i>SLC6A4</i> intron 2) and receptor gene (<i>5HTR2AT102C</i>) in individuals who died of suicide. The study compares the serum levels of serotonin between the cases and controls. <b><i>Methods:</i></b> We conducted a case-control study with 120 cases and 126 controls. Socio-economic details of the subjects were collected using a semi-structured proforma, and psychological autopsy was used to collect details of medical and other clinical conditions. Blood was drawn after taking informed consent and serum levels of serotonin were estimated by enzyme-linked immunosorbent assay. Genotyping was performed using appropriate primers followed by polymerase chain reaction and a restriction fragment length polymorphism. <b><i>Results:</i></b> Mean age was 32.59 ± 12.58 for cases and 33.64 ± 9.78 for controls. The risk-associated LL genotype of <i>5HTTLPR</i> was higher among cases. The heterozygous 12/10 genotype of <i>SLC6A4</i> intron 2 polymorphism was increased among controls. Serum levels of serotonin were lower among cases. Variant genotypes of all the 3 polymorphisms showed significant interaction (OR = 39.26) indicating that this model may increase suicidal tendency. <b><i>Conclusion:</i></b> The findings of this study suggest that low serum levels of serotonin and two variants of the serotonin gene may influence suicide behaviour in a south Indian population.