Genetic polymorphisms associated with circadian rhythm dysregulation provide new perspectives on bipolar disorder

Bipolar Disord. 2018 Sep;20(6):515-522. doi: 10.1111/bdi.12624. Epub 2018 Feb 13.

Abstract

Objectives: The objective of this study was to present a broad view of how genetic polymorphisms in genes that control the rhythmicity and function of circadian rhythm may influence the etiology, pathophysiology and treatment of bipolar disorder (BD).

Methods: A bibliographic search was performed to identify and select papers reporting studies on variations in circadian genes and BD. A search of Medline, Google Scholar, Scopus, and Web of Science was carried out to review the literature.

Results: Several studies provide evidence of contributions of variations in circadian genes to disease etiology, pathophysiological variations and lithium drug response. Dysfunction of the sleep-wake cycle, an important brain function regulator, is indicated as the primary means by which circadian gene variations act in mood disorders.

Conclusions: Investigations of the effects of circadian genes have suggested that the chronotype offers hope for guiding and improving management of patients with BD. However, BD is a disease of a complex nature and presents multiple endophenotypes determined by different associations between genetics and the environment. Thus, new genomic studies to delimit variations that may help improve the clinical condition of these patients are extremely important.

Keywords: bipolar disorder; circadian genes; circadian rhythm; genetic polymorphisms.

Publication types

  • Review

MeSH terms

  • ARNTL Transcription Factors / genetics
  • Antimanic Agents / therapeutic use
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / psychology
  • CLOCK Proteins / genetics
  • Cell Cycle Proteins / genetics
  • Chronobiology Disorders / genetics
  • Chronobiology Disorders / psychology
  • Circadian Rhythm / genetics*
  • Endophenotypes
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Lithium Compounds / therapeutic use
  • Mood Disorders / complications
  • Period Circadian Proteins / genetics
  • Polymorphism, Genetic
  • Sleep Disorders, Circadian Rhythm / genetics*
  • Sleep Disorders, Circadian Rhythm / psychology

Substances

  • ARNTL Transcription Factors
  • BMAL1 protein, human
  • Antimanic Agents
  • Cell Cycle Proteins
  • GNB3 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Lithium Compounds
  • PER2 protein, human
  • PER3 protein, human
  • Period Circadian Proteins
  • TIMELESS protein, human
  • CLOCK Proteins
  • CLOCK protein, human
  • Heterotrimeric GTP-Binding Proteins