Suicide attempt and genes : psychiatric and genetic characteristics of suicide attempters

Suicide affects an appreciable number of people in all societies. Finding genes that predispose to suicidal behavior may help to identify individuals at risk and an appropriate counseling and support can be extended to them. The studies of the present thesis focus on suicide attempt.

In order to characterize suicide attempters, DSM-III-R/DSM-IV classification, Axes I-V were used. Ninety-nine per cent of the patients had at least one Axis I diagnosis. Mood disorders were most common, followed by anxiety disorders and substance use disorders. Personality disorders on Axis Il were diagnosed in 56% of the patients. The most common personality disorder was borderline personality disorder. This diagnosis was more common among women. Axis III disorders were found in 45%. Suicide attempters with both Axis I and II diagnoses were more impaired in their functioning, according to Axis V, in the presence of severe stress (Axis IV) than those with only Axis I disorders.

Association studies were performed in order to identify genes relevant in suicidal behavior and to elucidate how these may influence the psychopathology and personality of the individual. Genetic markers investigated were: Tyrosine hydroxylase (TH), Dopamine receptor D4 (DRD4), Tryptophan hydroxylase (TPH), serotonin transporter (SERT) and serotonin receptor 2A (5-HT2A). In the association study investigating the TH polymorphism, a significant difference in the TH allelic distribution was observed among the suicide attempters with a diagnosis of adjustment disorder. Among these patients, carriers of a specific TH allele (T8) was significantly overrepresented. The study indicated that genetic variation at the TH locus is related to adjustment disorder and/or suicidal behavior. As for the DRD4, TPH, SERT and 5-HT2A polymorphisms, no significant association between suicide attempts and these polymorphisms was observed, indicating major/moderate effect on the predisposition to suicide attempt. Personality traits may contribute to suicidal behavior and may show strong relationships with the investigated genes. Therefore, associations between personality (NEO PI-R) in healthy subjects and genes were studied.

The Neuroticism dimension was indicated with higher scores for the T8 allele carriers. Further analyses with regard to the Neuroticism facets revealed significant differences for Angry Hostility and Vulnerability, with higher scores for the T8 carriers. This can be interpreted as consistent with the data reported above on TH and suicide attempters. No association between personality, characterized by the Extraversion dimension and the long form of the DRD4 polymorphism was observed. Our investigation did not yield evidence for association between the TPH polymorphism and personality.

List of scientific papers

I. Persson ML, Runeson BS, Wasserman D (1999). Diagnoses, psychosocial stressors and adaptive functioning in attempted suicide. Ann Clin Psychiatry. 11(3):119-128.
https://pubmed.ncbi.nlm.nih.gov/10482121

II. Persson ML, Wasserman D, Geijer T, Jönsson EG, Terenius L (1997). Tyrosine hydroxylase allelic distribution in suicide attempters. Psychiatry Res. 72(2):73-80.
https://pubmed.ncbi.nlm.nih.gov/9335198

III. Persson ML, Wasserman D, Jönsson EG, Bergman H, Terenius L, Gyllander A, Neiman J, Geijer T. Search for influence of the tyrosine hydroxylase (TCAT)n repeat polymorphism on personality traits. [Submitted]

IV. Persson ML, Geijer T, Wasserman D, Rockah R, Frisch A, Michaelovsky E, Jönsson EG, Apter A, Weizman A (1999). Lack of association between suicide attempt and a polymorphism at the dopamine receptor D4 locus. Psychiatr Genet. 9(2):97-100.
https://pubmed.ncbi.nlm.nih.gov/10412189

V. Persson ML, Wasserman D, Frisch A, Jönsson EG, Bergman H, Geijer T. Dopamine D4 receptor gene polymorphism and personality traits in healthy volunteers. [Submitted]

VI. Geijer T, Frisch A, Persson ML, Wasserman D, Rockah R, Michaelovsky E, Apter A, Jönsson EG, Nöthen MM, Weizman A. Search for association between suicide attempt and serotonergic polymorphisms. Psychiatric Genet. [Accepted]

VII. Geijer T, Frish A, Persson ML, Wasserman D, Rockah R, Michaelovsky E, Apter A, Jönsson EG, Bergman H, Weizman A. Search for influence of the tryptophan hydroxylase A218C polymorphism on personality traits. [Submitted]