Clock Genes and Altered Sleep–Wake Rhythms: Their Role in the Development of Psychiatric Disorders

Annaëlle Charrier,Pierre Roubertoux,Sylvie Tordjman,Bertrand Olliac

doi:10.3390/ijms18050938

Abstract

In mammals, the circadian clocks network (central and peripheral oscillators) controls circadian rhythms and orchestrates the expression of a range of downstream genes, allowing the organism to anticipate and adapt to environmental changes. Beyond their role in circadian rhythms, several studies have highlighted that circadian clock genes may have a more widespread physiological effect on cognition, mood, and reward-related behaviors. Furthermore, single nucleotide polymorphisms in core circadian clock genes have been associated with psychiatric disorders (such as autism spectrum disorder, schizophrenia, anxiety disorders, major depressive disorder, bipolar disorder, and attention deficit hyperactivity disorder). However, the underlying mechanisms of these associations remain to be ascertained and the cause–effect relationships are not clearly established. The objective of this article is to clarify the role of clock genes and altered sleep–wake rhythms in the development of psychiatric disorders (sleep problems are often observed at early onset of psychiatric disorders). First, the molecular mechanisms of circadian rhythms are described. Then, the relationships between disrupted circadian rhythms, including sleep–wake rhythms, and psychiatric disorders are discussed. Further research may open interesting perspectives with promising avenues for early detection and therapeutic intervention in psychiatric disorders.

Highlights

Circadian Rhythms and Their Molecular MechanismsThe function of the body is subject to different biological rhythms, the circadian one being keyed to a cycle of a 24-h day corresponding approximately to the 24-h light/dark cycle of the Earth’s rotation
It is noteworthy that sleep disorders are not specific to autism spectrum disorder (ASD) given that they are observed in ASD individuals with intellectual disability (ID), ID individuals without ASD, and individuals with brain injury as well as ID, suggesting a possible overlap between ASD and ID
The association between clock genes and ASD was confirmed by a more recent study [168] reporting mutations in other circadian clock genes (Per2, Per3, circadian locomotor output cycles kaput (Clock), brain and muscle ARNT-like protein 1 (Bmal1), Tim, Cry1, Cry2, D-site-binding protein (Dbp) and Ck1ε) in ASD patients. These findings suggest that the circadian rhythm abnormalities observed in ASD may be linked to abnormalities of the circadian clock genes

Summary

Introduction

Circadian Rhythms and Their Molecular MechanismsThe function of the body is subject to different biological rhythms, the circadian one being keyed to a cycle of a 24-h day corresponding approximately to the 24-h light/dark cycle of the Earth’s rotation. The range of the internal clock period for healthy adults is 24 h and 11 ± 16 min but it is set back to a 24-h cycle each day by exposure to morning light and to external clocks [1] This rhythm regulates most of our biological and behavioral functions. No rigorous study of prevalence of sleep disorders was conducted in bipolar spectrum disorder and depression-related disorders but altered patterns of clock genes were reported in these disorders [16,17]. High rates of sleep problems and mental disorders have been reported in shift workers, including insomnia, fatigue, anxiety and depression [18,19,20,21,22,23,24]. It is noteworthy that altered patterns of clock genes were reported in shift workers [25,26,27]

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Results

Conclusion