The influence of four serotonin-related genes on decision-making in suicide attempters.
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.
Jollant
Fabrice
F
Université Montpellier 1, Montpellier, France. f-jollant@chu-montpellier.fr
Buresi
Catherine
C
Guillaume
Sébastien
S
Jaussent
Isabelle
I
Bellivier
Frank
F
Leboyer
Marion
M
Castelnau
Didier
D
Malafosse
Alain
A
Courtet
Philippe
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D003657:Decision Making; D005260:Female; D006801:Humans; D007484:Iowa; D007859:Learning Disabilities / Q000235:genetics / Q000523:psychology; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics*; D019964:Mood Disorders / Q000235:genetics* / Q000523:psychology; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013406:Suicide, Attempted / Q000523:psychology*; D014365:Tryptophan Hydroxylase / Q000235:genetics*
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C497467:TPH1 protein, human; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase; D008995:Monoamine Oxidase