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

BACKGROUND: Previously, 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. METHODS: The 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. RESULTS: An 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. LIMITATIONS: Relatively small number of patients studied and insufficient correction for multiple testing. CONCLUSIONS: These 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.

TEMPS-A and long-term lithium response: positive correlation with hyperthymic temperament.

BACKGROUND: Lithium is still regarded as a cornerstone for the long-term treatment of bipolar disorder. The best response to lithium is associated with clinical features of episodic clinical course, complete remission, bipolar family history and low psychiatric comorbidity. However, a specific personality profile for the best lithium response was not estimated so far. Such a possibility occurred with an advent of temperament scale for bipolar disorder and of an ability to quantitatively assess lithium prophylactic response. METHODS: The study was performed on 71 patients with bipolar mood disorder (21 males, 50 females), aged 31-82 (59±12) years, which have been treated with lithium carbonate for at least 5 years (5-37 years, mean 15 years). In all patients, the assessment of five temperaments of TEMPS-A scale (depressive, cyclothymic, hyperthymic, irritable and anxious) was done, and correlated with the quality of lithium prophylaxis according to Alda scale. RESULTS: The mean scores for five temperaments of TEMPS-A were not significantly different in male and female patients. The response to lithium correlated significantly positively with hyperthymic temperament score (r=0.31, p=0.009), and negatively with anxiety (r=-0.27, p=0.022), cyclothymic (r=-0.26, p=0.032), and depressive (r=-0.23, p=0.052) temperaments scores. LIMITATIONS: Relatively small number of patients. CONCLUSIONS: The main finding of the study is an association of lithium response with hyperthymic temperament. This positive correlation as well as other negative correlations between lithium response and TEMPS-A temperaments are discussed in view of clinical and genetic findings in bipolar patients.