¹Department of Psychiatry, Carémeau Hospital, Nîmes, France

²Department of Psychological Medicine and Psychiatry, Lapeyronie Hospital, INSERM E99-30, Montpellier, France

³Department of Psychiatry, Henri Mondor and Albert Chenevier Hospitals, Créteil, France

⁴University Department of Psychiatry, La Colombière Hospital, INSERM E99-30, Montpellier, France

⁵Division of Neuropsychiatry, Department of Psychiatry, Geneva University Hospital, Geneva, Switzerland

Correspondence to: P Courtet, Department of Psychological Medicine and Psychiatry, Lapeyronie Hospital, 34295 Montpellier Cedex 5, France. E-mail: courtet@aol.com

^aThese two authors contributed equally to this work and they are listed in alphabetical order.

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 (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 (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. Molecular Psychiatry (2001) 6, 268-273.

tryptophan hydroxylase; genetic polymorphisms; suicidal behavior; association study