Association between GSK3β gene and increased impulsivity in bipolar disorder.
Bipolar patients present increased levels of impulsivity even during remission periods. It is known that this dimensional trait negatively impacts on the course of illness and worsens their prognosis and outcome. Evidence from both basic and clinical researches supports that Lithium (Li) may decrease impulsivity. Owing to the fact that Li inhibits both glycogen synthetase kinase-3 (GSK3) isoenzimes, our aim was to analyze the potential impact of genetic variants located at the GSK3 α and β genes on impulsivity levels in a bipolar sample. Our sample consisted of 199 unrelated Caucasian bipolar outpatients who were recruited from the Bipolar Disorder Unit of the Hospital Clinic of Barcelona and from primary care settings from Oviedo. Four polymorphisms at the GSK3 α and β genes were genotyped in order to analyze the impact of genetic variability on impulsivity as measured by the BIS-11 scale. Single SNP analysis showed that patients carrying T and G alleles at the rs1732170-GSK3β and the rs334558-GSK3β, respectively, presented increased levels of attentional impulsivity compared to non-carriers. These results were also confirmed by haplotype analysis. Our results suggest that genetic variability at GSK3β gene is associated to increased impulsivity in bipolar patients.
Bipolar Disorder Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
Esther
E
Jiménez
Department of Animal Biology, Anthropology Section, Faculty of Biology, University of Barcelona, IBUB, CIBERSAM, Instituto de Salud Carlos III, Barcelona, Catalonia, Spain.
Bárbara
B
Arias
Department of Animal Biology, Anthropology Section, Faculty of Biology, University of Barcelona, IBUB, CIBERSAM, Instituto de Salud Carlos III, Barcelona, Catalonia, Spain.
Marina
M
Mitjans
Bipolar Disorder Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
Jose M
JM
Goikolea
Institut Clinic de Neurociencies, Hospital Clinic, Barcelona, Catalonia, Spain.
Esther
E
Roda
Institut Clinic de Neurociencies, Hospital Clinic, Barcelona, Catalonia, Spain.
Victoria
V
Ruíz
Institut Clinic de Neurociencies, Hospital Clinic, Barcelona, Catalonia, Spain.
Ana
A
Pérez
Department of Psychiatry, School of Medicine, University of Oviedo, CIBERSAM, Instituto de Neurociencias del Principado de Asturias, INEUROPA, Oviedo, Spain; Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain.
Pilar A
PA
Sáiz
Department of Psychiatry, School of Medicine, University of Oviedo, CIBERSAM, Instituto de Neurociencias del Principado de Asturias, INEUROPA, Oviedo, Spain; Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain.
M Paz
MP
García-Portilla
Department of Psychiatry, School of Medicine, University of Oviedo, CIBERSAM, Instituto de Neurociencias del Principado de Asturias, INEUROPA, Oviedo, Spain.
Patricia
P
Burón
Department of Psychiatry, School of Medicine, University of Oviedo, CIBERSAM, Instituto de Neurociencias del Principado de Asturias, INEUROPA, Oviedo, Spain; Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain.
Julio
J
Bobes
Bipolar Disorder Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. Electronic address: evieta@clinic.ub.es.
Eduard
E
Vieta
Bipolar Disorder Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
Antoni
A
Benabarre
D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D003430:Cross-Sectional Studies; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007175:Impulsive Behavior; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D013030:Spain
C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha
Bipolar disorder; GSK3β; Genetics; Glycogen synthetase kinase-3; Impulsivity; Lithium