Two articles in the current issue of Molecular Psychiatry from researchers in France and in Switzerland have identified variations (polymorphisms) in two genes that are associated with suicidality -- the tendency to kill oneself. These findings suggest that suicidality may have a genetic basis.

In the first article, "Suicide attempts and the tryptophan hydroxylase gene," the authors, from the Department of Psychiatry, Carémeau Hospital, Nimes, France; Department of Psychological Medicine and Psychiatry, Lapeyronie Hospital and University Department of Psychiatry, La Colombière Hospital Montpellier, France; Henri Mondor and Albert Chenevier Hospitals, Créteil, France; and the Department of Psychiatry, Geneva University Hospital, Geneva, Switzerland, point out the following:

A specific genetic vulnerability for suicidal behavior is strongly suggested by the results of epidemiological genetics studies. Several lines of evidence suggest that regulation of serotonin neurotransmission is a key factor for this vulnerability.

Recent studies have investigated the involvement of the gene coding for the tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis, in the genetic susceptibility to suicidal behavior.

In this case-control study, the authors investigated seven polymorphisms spanning the entire TPH gene in 231 suicide attempters and 281 controls.

Significant associations were found between variants within the 3' noncoding region and suicide attempt. The association was strongest for subjects who had attempted suicide by violent means and who had a history of major depression.

The results, 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.

(Citation source: Molecular Psychiatry 2001 Volume 6, number 3, pages 268-273.)

In the second article, "Association between violent suicidal behavior and the low activity allele of the serotonin transporter gene," the authors, from the Department of Psychological Medicine and Psychiatry, Lapeyronie Hospital and University Department of Psychiatry, La Colombière Hospital Montpellier, France; Department of Psychiatry, Carémeau Hospital, Nimes, France and the Department of Psychiatry, Geneva University Hospital, Geneva, Switzerland, declare:

There is compelling evidence that serotonin system dysfunction is associated with suicidal behavior. Some data suggest that this association is stronger with violent suicidal behavior.

The genetic susceptibility to suicidal behavior may involve a functional polymorphism (S/L alleles) in the promoter region of the serotonin transporter gene. The S allele of this gene has been found to be associated with a lower level of expression of the gene and lower leve]s of 5-HT uptake.

The authors genotyped 51 violent suicide attempters and 139 controls with no history of suicidal behavior, all of West European Caucasian origin.

The frequencies of the S allele and the SS genotype were significantly higher in the violent suicide attempters than in the controls. The odds ratio for the SS genotype vs the LL genotype was 3.63 (95% CI (l.Z7-10.40)).

Together with previous reports, the present finding suggests that a change in expression of the gene encoding the 5-HT transporter may be involved in violent suicide behavior.

(Citation source: Molecular Psychiatry 2001 Volume 6, number 3, pages 338-341.)

For further information on both articles, please contact Dr. Philipe Courtet, Department of Psychological Medicine and Psychiatry, Lapeyronie Hospital, 34295 Montpellier Cedex 5, France. Dr. Courtet can be reached by email at this address.

Molecular Psychiatry is published by the Nature Publishing Group. It is edited by Julio Licinio, M.D., Professor of Psychiatry, UCLA Gonda Center, Los Angeles, CA.

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Molecular Psychiatry

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06-Apr-2001