Evaluation of the Association between Lithium Treatment andGSK3β Polymorphism in Bipolar Disorder Patients

Objective: There is a lack of evidence regarding clinical predictors for the treatment response to lithium, which is the main stay treatment option for bipolar disorder. Studies that examined the mechanistic action of lithium revealed that glycogen synthase kinase 3β (GSK-3β) enzymeinhibition was important in regard to treatment responses. Based on this background, we aimed to investigate the association between responses to lithium treatment and five different polymorphisms of GSK-3β. Method: Lithium treatment response scale (LTRS) scores for 100 patients diagnosed with bipolar disorders type I were calculated according to the hospital records. Blood samples were collected and genomic DNA was obtained using the MagNA Pure Compact automatic isolation method. The GSK-3β: rs17183904, rs17183897, rs34009575, rs34002644, and rs17183890 polymorphisms were analyzed by real time PCR. Results: In this cohort, the mean age of patients was 41.1±10.3 years, the mean age of disease onset was 24.5±8.2, and the mean LTRS score was 4.9±1.8. There was no statistically significant difference for LTRS scores between groups in terms of gender, marital status, level of education, and the type of first episode. LTRS was significantly higher in only the patients harbouring GSK-3β rs17183890 AG genotype (p=0.008, t:2.71). Interestingly, no differences were found for the remaining polymorphisms. Conclusion: The specific GSK-3β polymorphism that associated with lithium-response in our study may help to predict lithium responses and to develop individualized treatment. We presume that our pharmacogenomic findings may also provide important contributions to the clinical practice in regard to future evaluation of the treatment adherence and side effects. To obtain these goals, further genome-wide scanning studies conducted on larger sample cohorts are required.