title: Wolfram syndrome and suicide: Evidence for a role of WFS1 in suicidal and impulsive behavior.
abstract: 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.
authors.affiliation: McGill Group for Suicide Studies, Douglas Hospital, McGill University, Montreal, Canada.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Sequeira
authors.forename: Caroline
authors.initials: C
authors.lastname: Kim
authors.forename: Monique
authors.initials: M
authors.lastname: Seguin
authors.forename: Alain
authors.initials: A
authors.lastname: Lesage
authors.forename: Nadia
authors.initials: N
authors.lastname: Chawky
authors.forename: Alex
authors.initials: A
authors.lastname: Desautels
authors.forename: Michel
authors.initials: M
authors.lastname: Tousignant
authors.forename: Claude
authors.initials: C
authors.lastname: Vanier
authors.forename: Olivier
authors.initials: O
authors.lastname: Lipp
authors.forename: Chawki
authors.initials: C
authors.lastname: Benkelfat
authors.forename: Guy
authors.initials: G
authors.lastname: Rouleau
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
mesh_terms: 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
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein