Suicide risk of depressive patients increasing with genetic disposition

Receptor gene NTRK2 mutations increase suicidal tendency

Research into genetic causes of suicidal behaviour of depressive patients associates variants of tyrosin kinase 2 receptor gene (NTRK2) with an elevated risk of attempted suicide. As a binding site for the factor BDNF (brain derived neurotrophic factor), NTRK2 has an important function for a target-oriented setting up of networks of nerve cells and thus for a well-balanced neuronal communication. With the newly-discovered mutations, the scientists of the Max Planck Institute of Psychiatry have established the study of the molecular causes of suicidal behaviour.

Worldwide, there are roughly about 10 to 20 million suicide attempts and about 1 million actual suicides per year. In Germany, 9.402 people killed themselves in 2007; that is a rate of 1,1% of all deaths. Among the under thirty-year-olds, even one out of four deaths results from attempted suicide. The general lifelong prevalence for trying to commit suicide is reported to be three to five per cent, whereby higher numbers are determined among psychiatric patients and nearly one third of the patients suffering from depression try to kill themselves. Twin studies and family studies suggest that, irrespective of possible psychiatric diseases, suicides and attempted suicides have got a genetic basis.

In their study, Martin Kohli and colleagues at the MPI dealt with the question if there are genetic differences between depressive patients trying to respectively not trying to commit suicide. In their analysis, they concentrated on the genes of the nerve nutritient factor BDNF and its receptor NTRK2, which verifiably appear in the brain tissue of suicide victims in smaller quantities. At first, they examined variations in individual gene components of 366 healthy people and 394 patients suffering from various affective disorders, of whom 113 had tried to kill themselves. Whereas no significant differences could be detected within the BDNF gene, even three gene variants associated with an elevated risk of trying to commit suicide were identified within the NTRK2 gene. Indeed, the risk of suicidal behaviour of depressive patients increases by the 4,5 fold, if all three unfavourable gene variants act together (see Figure).

Figure legend: Illustration of the relative risk of trying to commit suicide depending whether the different gene variants at rs10868235 and rs1147198 exist at the same time.

Additional studies in a German patient group with 744 depressive patients and a non-psychiatric Afro-American patient group comprising 921 persons, of whom 152 respectively 119 had tried to kill themselves, arrived at the same conclusion. Due to differences in diagnosis and background of the examined patients and due to the unverifiable association between suicide attempts and depression per se, the mutations discovered in the NTRK2 gene seem to be specific to suicidal behaviour.

Apart from causal research, with their new results, the scientists also hope to be able to improve prevention and therapy of the persons concerned in the long run. "Our study for the first time proves a genetic association of NTRK2 with suicidal behaviour, thus opening up to us the opportunity to carry out detailed studies in order to identify possible fresh therapeutic attempts at this receptor", Dr. Elizabeth Binder explained.

Original publication:

Martin A. Kohli, Daria Salyakina, Andrea Pfennig, Susanne Lucae, Sonja Horstmann, Andreas Menke, Stefan Kloiber, Johannes Hennings, Bekh B. Bradley, Kerry J. Ressler, Manfred Uhr, Bertram Müller-Myhsok, Florian Holsboer, Elisabeth B. Binder

Genetic Mutations Associated With Suicide Risk Among Patients With Depression

Archives of General Psychiatry 2010;67[4]:(doi:10.1001/archgenpsychiatry.2009.201

For further information, please contact:

Dr. Barbara Meyer

Public relations

Max Planck Institute of Psychiatry

Phone: +49 89 30622-616

Fax: + 49 89 30622-348

Email: bmeyer[a]mpipsykl.mpg.de