The influence of four serotonin-related genes on decision-making in suicide attempters

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2007-07, Vol.144B (5), p.615-624
• Main Authors: Jollant, Fabrice, Buresi, Catherine, Guillaume, Sébastien, Jaussent, Isabelle, Bellivier, Frank, Leboyer, Marion, Castelnau, Didier, Malafosse, Alain, Courtet, Philippe
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Aged; attempted suicide; Biological and medical sciences; Decision Making; Female; Humans; Iowa; Learning Disorders - genetics; Learning Disorders - psychology; learning process; Male; Medical genetics; Medical sciences; Middle Aged; Monoamine Oxidase - genetics; Mood Disorders - genetics; Mood Disorders - psychology; Polymorphism, Genetic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; serotonin; Serotonin Plasma Membrane Transport Proteins - genetics; single nucleotide polymorphism; Suicide; Suicide, Attempted - psychology; Tryptophan Hydroxylase - genetics
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.30467

Genetic factors have been associated with the vulnerability to suicidal behavior. We previously reported decision‐making impairment in suicide attempters and hypothesized that these cognitive alterations may represent an endophenotype of suicidal behavior. In this study, we aimed to investigate the influence of four serotonin‐related genes relevant to suicidal behavior on decision‐making, in a large population of suicide attempters. The Iowa Gambling Task was used to assess decision‐making in 168 patients with a personal history of attempted suicide. Patients were genotyped for four serotonergic polymorphisms: 5HTTLPR, TPH1 A218C, MAOA u‐VNTR, and TPH2 rs1118997. Patients carrying the 5HTTLPR‐ll and ‐sl, TPH1‐CC and ‐AC, MAOA‐HH (in women) and TPH2‐AA genotypes significantly improved their performance during the task, suggesting a genetic modulation of the learning process required for advantageous decision‐making. In contrast, genotypes previously associated with a higher risk of suicidal behavior, a greater sensitivity to the environment and a higher propensity to negative feelings are those conferring poorer learning abilities. We hypothesize that the influence of genetic factors on the vulnerability to suicidal behavior may partly be achieved through their modulation of decision‐making and particularly its learning component. © 2007 Wiley‐Liss, Inc.