Polymorphism of circadian clock genes and temperamental dimensions of the TEMPS-A in bipolar disorder

BackgroundPreviously, we found correlations between lithium efficacy in bipolar disorder and temperamental dimensions of the TEMPS-A and also genes involved in the regulation of biological rhythms (“clock” genes). Here, were attempted to investigate an association between multiple, single nucleotide polymorphisms (SNPs) of four clock genes (CLOCK, ARNTL, TIM, PER3) and temperamental dimensions of the TEMPS-A, in bipolar patients.MethodsThe study included 70 patients with bipolar disorder (20 males, 50 females), with a mean age of 59±12 years. The TEMPS-A questionnaire, 110 questions version, was used assessing five temperament domains: depressive, cyclothymic, hyperthymic, irritable and anxious. Genotyping was done for 9 SNPs of the CLOCK gene, 18 SNPs of the ARNTL gene, 6 SNPs of the TIM gene and 5 SNPs of the PER3 gene.ResultsAn association with hyperthymic temperament was found for three, and with anxious temperament for four SNPs of the ARTL gene. An association of cyclothymic temperament was found with two SNPs of the TIM gene and of depressive temperament with one SNP of the PER3 gene. No association was observed with SNPs of the CLOCK gene.LimitationsRelatively small number of patients studied and insufficient correction for multiple testing.ConclusionsThese results may suggest that the ARNTL, TIM and PER3 genes may be associated with temperamental dimensions measured by the TEMPS-A, each of this gene being specific to given temperamental dimension. Of special interest may be the polymorphisms of ARNTL gene also connected with predisposition to bipolar mood disorder and/or lithium response.