The impact of glycogen synthase kinase 3β gene on psychotic mania in bipolar disorder patients

ObjectiveThe aim of this study was to examine the relationships between glycogen synthase 3β gene polymorphisms and bipolar I disorder, manic in a Korean sample.MethodsPatients with bipolar disorder (n = 118) and a control group (n = 158) were assessed by genotyping for GSK3β single nucleotide polymorphisms (SNPs) − 1727A/T and − 50C/T. The patients were divided into two groups according to the presence of psychotic symptoms (psychotic mania, n = 92; non-psychotic mania, n = 26) and also divided based on gender and age of onset. The severity of symptoms was measured using the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS).ResultsThere were no significant differences in the genotype distributions or allelic frequencies of GSK3β polymorphisms and gender between patients with bipolar disorder and a normal control group. According to haplotype analysis, there was no association between these two groups. However, analysis of the age of onset of bipolar disorder revealed significant differences in genotype and allele distributions among the patients. Patients who were homozygous for the wild-type variant (TT) had an older age of onset than carriers of the mutant allele (A/A: 27.4 ± 9.1; A/T: 30.1 ± 11.8; T/T: 42.3 ± 19.9; p = 0.034). We detected differences in allele frequencies of the GSK3β − 1727A/T polymorphism between the psychotic mania group and the non-psychotic mania group.ConclusionThis study suggests that GSK3β polymorphisms are not associated with bipolar disorder. However, the GSK3β SNP − 1727A/T is associated with age of onset and presence of psychotic symptoms in bipolar disorder.

Research Highlights► GSK3β plays a key role in the etiology and therapeutic action for bipolar disorder. ► GSK-3β gene SNP-1727A/T was associated with psychotic mania in bipolar I disorder. ► GSK3β polymorphisms have no association between bipolar disorder and control group. ► GSK3β gene is associated with onset age and psychotic symptom in bipolar disorder.