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.