Wolfram syndrome and suicide: Evidence for a role of WFS1 in suicidal and impulsive behavior.
There is evidence suggesting that subjects affected with the Wolfram syndrome (WFS) and normal carriers present an increased risk of psychiatric disorders, particularly depression and suicidal behavior. We investigated a possible role of the gene involved in WFS (WFS1) in the neurobiology of suicide and the potential modulatory effect on traits associated to suicidal behavior. Genetic variation at WFS1 (H611R, R456H, and I333V) was investigated in 111 suicide victims and 129 normal controls. Possible effects on psychopathology and behavioral traits were investigated in a subsample of suicide cases (N = 31) for whom phenotyping was carried out by means of structured psychiatric interviews and questionnaires adapted for psychological autopsies. We found a significantly higher frequency of the 611R/611R genotype in suicide completers as compared to controls (chi(2) = 19.21, df=2, P = 0.001). Suicide completers with this genotype had higher scores on measures of impulsivity (t = -3.15, df = 15.3, P = 0.006); novelty seeking (NS) (t = -3.35, df = 13.8, P = 0.005); and conversely, lower scores of persistence (t = 2.4, df = 16.6, P = 0.028). Scores of impulsivity and NS remained higher in subjects with the associated genotype after adjusting for age, gender, and psychopathology. These results suggest a role for WFS1 in the pathophysiology of impulsive suicide, and are consistent with previous clinical reports suggesting an increased risk of suicidal behavior in WFS homozygotes and heterozygotes. However, these findings are preliminary and should be confirmed in independent samples.
Sequeira
Adolfo
A
McGill Group for Suicide Studies, Douglas Hospital, McGill University, Montreal, Canada.
Kim
Caroline
C
Seguin
Monique
M
Lesage
Alain
A
Chawky
Nadia
N
Desautels
Alex
A
Tousignant
Michel
M
Vanier
Claude
C
Lipp
Olivier
O
Benkelfat
Chawki
C
Rouleau
Guy
G
Turecki
Gustavo
G
D000328:Adult; D016022:Case-Control Studies; D018703:Founder Effect; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007175:Impulsive Behavior / Q000209:etiology / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense; D010641:Phenotype; D012720:Severity of Illness Index; D013405:Suicide; D014929:Wolfram Syndrome / Q000150:complications* / Q000235:genetics
D008565:Membrane Proteins; C114987:wolframin protein