Akademik Veri Yönetim Sistemi
37th ECNP Congress 2024, Milan, İtalya, 21 - 24 Eylül 2024, ss.1
Background: Bipolar disorder (BD) significantly disrupts biological rhythm [1, 2]. The first-line drugs used in the treatment are mood stabilizers, the most commonly used being lithium and valproic acid (VPA). Treatment response is variable and associated with many factors, including circadian rhythm and chronotype [4]. As shown in animal studies, VPA may interfere with circadian rhythm [3]. We therefore aimed to explore whether treatment response to VPA is related to (i) genetic variations [COMT Val158Met (rs4680), CLOCK 3111T/C (rs1801260), GSK3-ß -50T/C (rs334558) polymorphisms], (ii) social and circadian rhythm and (iii) chronotype.
Methods: 94 patients aged between 18 and 65 with BD who had been using VPA for at least one month were included. Hamilton Depression Rating Scale (HAM-D), Young Mania Rating Scale, Biological Rhythm Interview for Assessment in Neuropsychiatry, Morningness Eveningness Questionnaire, Alda Scale, Social Rhythm Metric-5 (SRM-5) and Unified Parkinson's Disease Rating Scale-Motor Examination were employed. Kruskal-Wallis or One-Way ANOVA was used for comparisons among three polymorphism groups, Mann-Whitney U test or Independent Samples T-test for two groups, and Chi-Square Test or Fisher's Exact Test for dichotomous variables.
Results: Carriers of the C allele of the CLOCK 3111T/C polymorphism had later age of onset, lower number of previous mood episodes, more regular social and circadian rhythms and fewer daily mood swings. We also demonstrated that A/A genotype of COMT Val158Met polymorphism is advantageous, whereas C/T genotype of GSK3-ß -50T/C polymorphism is disadvantageous in terms of response to VPA maintenance therapy. Moreover, regarding COMT Val158Met polymorphism, carriage of A allele has been associated with social rhythm irregularity and more frequent family history of a psychiatric disorder.
We found that the duration of the disease, the number of previous manic/hypomanic episodes, HAM-D total score, SRM-5 mood swing score, and duration of VPA exposure each have a negative correlation with the Alda Scale A score. Morningness chronotype was associated with more regular biological rhythm and better treatment response. Linear regression analyses showed that response to VPA treatment was predicted by a model consisting of the duration of disease, HAM-D total score, the number of previous manic/hypomanic episodes, SRM-5 mood swing score and duration of VPA exposure variables [F(5)=9.34,R2=0.32,p<0.001].
Conclusions: These findings suggest that the C allele of the CLOCK 3111T/C polymorphism is protective in terms of the number of attacks, regularity of biological rhythm and mood swings. A/A genotype of COMT Val158Met polymorphism and C/T genotype of GSK3-ß -50T/C polymorphism are also associated with an improved response to VPA maintenance treatment. Treatment response is negatively correlated with the duration of disease, the number of previous manic/hypomanic episodes, HAM-D total score, SRM-5 mood swing score and duration of VPA exposure. Morningness is advantageous for regular biological rhythm and better response to VPA maintenance therapy. The total number of manic/hypomanic episodes, as well as total duration of VPA exposure, contributes to treatment response more predominantly than other independent variables included in the regression analyses.
References
[1] Abreu T., Bragança M., 2015. The bipolarity of light and dark: a review on bipolar disorder and circadian cycles. J. Affect. Disord. 185, 219-229. [2] Alloy L.B., Ng T.H., Titone M.K., Boland E.M., 2017. Circadian rhythm dysregulation in bipolar spectrum disorders. Curr. Psychiatry Rep. 19, 1-10. [3] McCarthy M.J., Wei H., Nievergelt C.M., Stautland A., Maihofer A.X., Welsh D.K., Shilling P., Alda M., Alliey-Rodriguez N., Anand A., 2019. Chronotype and cellular circadian rhythms predict the clinical response to lithium maintenance treatment in patients with bipolar disorder. Neuropsychopharmacology 44(3), 620-628. [4] Johansson A.-S., Brask J., Owe-Larsson B., Hetta J., Lundkvist G.B., 2011. Valproic acid phase shifts the rhythmic expression of Period2:: Luciferase. J. Affect. Disord. 26(6), 541-551.
Conflict of interest:
Disclosure statement: This abstract is financially supported by Ankara University Scientific Research Projects Coordination Office.