A relationship between response to lithium prophylaxis and T-50C polymorphism of glycogen synthase kinase-3β (GSK-3β) gene was investigated in 89 bipolar patients (41 male and 48 female) who have been taking lithium for at least 5 years. The patients were delineated as excellent responders, partial responders and non-responders to lithium. The results obtained suggest that this polymorphism may not be related to the degree of prophylactic lithium response.

Glycogen synthase kinase-3β (GSK-3β) has been implicated in the pathogenesis of major psychoses. In this paper, the T–50C polymorphism of the GSK-3β gene has been studied in patients with schizophrenia (n = 432), patients with bipolar disorder (n = 416) and in a healthy control group (n = 408). Consensus diagnosis by at least two psychiatrists was made for each patient, according to DSM-IV and ICD-10 criteria, using the Structured Clinical Interview for DSM-IV Axis I Disorders. Genotypes were established by the polymerase chain reaction-restriction fragment length polymorphism method. We have found a trend towards an association for the C allele in the whole group of schizophrenic patients (p = 0.088) and for the heterozygous T/C genotype of bipolar patients (0.095). Significant differences of genotype distribution and allele frequencies of the T–50C polymorphism were found in the female group of bipolar II patients (p = 0.015 for genotypes and p = 0.009 for alleles). In conclusion, this polymorphism may be associated with female gender in bipolar II disorder.

Several genes of the glutamatergic system have been implicated in both schizophrenia and bipolar disorder. The Src family tyrosine kinase FYN plays a key role in the interaction between brain-derived neurotrophic factor and glutamatergic receptor N-methyl-D-aspartate. Although no association between FYN gene polymorphisms and schizophrenia has been demonstrated, in our previous paper we found an association between FYN polymorphisms and cognitive test performance in schizophrenic patients. The aim of this study was to find a possible association of three polymorphisms of the FYN gene with bipolar disorder. We analyzed 425 bipolar patients and 518 control subjects. Genotypes of three analyzed polymorphisms, i.e. rs706895 (–93A/G in the 5′-flanking region), rs6916861 (Ex12+894T/G in the 3′-UTR) and rs3730353 (IVS10+37T/C in intron 10) were established by PCR-RFLP. A significant association was found between rs6916861 T/G and rs3730353 T/C polymorphisms of the FYN gene and bipolar disorder. These results were also significant in the subgroups of bipolar I and early-onset (<18 years) bipolar disorder patients. No association with –93 A/G polymorphism was found. Haplotype analysis revealed that rs6916861 T/G and rs3730353 T/C polymorphisms are in linkage disequilibrium (r2 = 0.86, D′ = 0.93 with 95% CI = 0.9–0.97). The results suggest that the glutamatergic FYN gene may be associated with bipolar disorder, particularly with type I illness and early age of onset.