Suicide attempts and the tryptophan hydroxylase gene

• Published in: Molecular psychiatry Vol. 6; no. 3; pp. 268 - 273
• Main Authors: ABBAR, M, COURTET, P, VESSAZ, M, MALAFOSSE, A, BURESI, C, BELLIVIER, F, LEBOYER, M, BOULENGER, J. P, CASTELHAU, D, FERREIRA, M, LAMBERCY, C, MOUTHON, D, PAOLONI-GIACOBINO, A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.05.2001
• Subjects: Adult; Adult and adolescent clinical studies; Biological and medical sciences; Brain Chemistry - genetics; Case-Control Studies; Causes of; Depression - genetics; Drug overdose; Enzymes; Female; Genetic aspects; Genetic diversity; Genetic polymorphisms; Genetic susceptibility; Humans; Hydroxylases; Impulsive behavior; Introns; Linkage Disequilibrium; Male; Medical sciences; Middle Aged; Neurosciences; Nonviolence; Phenotypes; Physiological aspects; Polymorphism; Polymorphism, Genetic; Psychiatrists; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Schizophrenia; Serotonin; Serotonin - metabolism; Suicidal behavior; Suicide; Suicide, Attempted; Suicides & suicide attempts; Susceptibility; Tryptophan; Tryptophan hydroxylase; Tryptophan Hydroxylase - genetics; Tryptophan Hydroxylase - metabolism; Violence; France; Case study; Human; Gene; Pathophysiology; Tryptophan 5-monooxygenase; Enzyme; Oxidoreductases; Suicide attempt
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/sj.mp.4000846

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme of serotonin synthesis. In this case-control study, we investigated whether the TPH gene was a susceptibility factor for suicidal behavior. Seven polymorphisms spanning the entire gene were studied in a case-control study including 231 individuals who had attempted suicide and 281 controls. Significant associations were found between variants in introns 7, 8 and 9 (chi(2) = 11.2, df = 1, P< 0.0008 for the allele distribution; these loci are in complete linkage disequilibrium) and in the 3' noncoding region (chi(2) = 30.94, P = 0.0014) and suicide attempt. The association was strongest for subjects who had attempted suicide by violent means and who had a history of major depression. No significant association was observed between suicide attempts and polymorphisms in the promoter, intron 1 and intron 3. The results presented here, and those of previous studies, suggest that a genetic variant of the 3' part of the TPH gene may be a susceptibility factor for a phenotype combining suicidal behavior, mood disorder and impulsive aggression.