The association between circadian clock gene polymorphisms and the phenotype of Bipolar Disorder: a systematic review

Abstract

Objective: This systematic review explores the link between circadian clock gene polymorphisms and the phenotypic presentation of Bipolar Disorder in adult individuals. By combining findings from numerous studies we aim to identify genetic factors that contribute and can eventually predict the clinical manifestations of BD. Methods: Searches were conducted through PubMed, ScienceDirect and PsychInfo, according to PRISMA guidelines. We retrieved relevant literature on circadian clock genes, namely CLOCK, ARNTL, TIMELESS, PER3, GSK3-B, RORB, among others. 18 studies including SNP analysis and VNTR repetitions were considered and associations with specific BD traits were identified and synthesized. Results: We found evidence of contribution of polymorphisms of circadian genes among several studies in what concerns the phenotypic presentation and the clinical characteristics of BD patients. CLOCK 3111 T/C SNP is strongly associated with illness recurrence, evening activity and sleep disturbances. CRY2 SNP rs10838524 is a strong predictor of a rapid cycling subtype. No individual genetic polymorphism was significantly related to treatment response. Conclusion: This systematic review sheds a light on the evolving understanding of circadian clock gene polymorphisms in the context of BD and its clinical and practical implications. The associations found emphasize the need for further research, giving an insight into possible individualized treatment approaches and refined risk assessment strategies for individuals with BD.