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Clock Genes, Circadian Rhythms, and Mood Disorders

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Pretty interesting shit.

Am J Med Genet B Neuropsychiatr Genet. 2018 Mar;177(2):181-198. doi:
10.1002/ajmg.b.32599. Epub 2017 Sep 13.

The role of CLOCK gene in psychiatric disorders: Evidence from human and animal

Schuch JB(1), Genro JP(2), Bastos CR(3), Ghisleni G(3), Tovo-Rodrigues L(4).

The circadian clock system drives daily rhythms in physiology, metabolism, and
behavior in mammals. Molecular mechanisms of this system consist of multiple
clock genes, with Circadian Locomotor Output Cycles Kaput (CLOCK) as a core
member that plays an important role in a wide range of behaviors. Alterations in 
the CLOCK gene are associated with common psychiatric disorders as well as with
circadian disturbances comorbidities. This review addresses animal, molecular,
and genetic studies evaluating the role of the CLOCK gene on many psychiatric
conditions, namely autism spectrum disorder, schizophrenia,
attention-deficit/hyperactivity disorder, major depressive disorder, bipolar
disorder, anxiety disorder, and substance use disorder. Many animal experiments
focusing on the effects of the Clock gene in behavior related to psychiatric
conditions have shown consistent biological plausibility and promising findings. 
In humans, genetic and gene expression studies regarding disorder susceptibility,
sleep disturbances related comorbidities, and response to pharmacological
treatment, in general, are in agreement with animal studies. However, the number 
of controversial results is high. Literature suggests that the CLOCK gene exerts 
important influence on these conditions, and influences the susceptibility to
phenotypes of psychiatric disorders.

© 2017 Wiley Periodicals, Inc.

DOI: 10.1002/ajmg.b.32599 
PMID: 28902457 


Neurosci Bull. 2015 Feb;31(1):141-59. doi: 10.1007/s12264-014-1495-3. Epub 2015
Feb 6.

Genetics and epigenetics of circadian rhythms and their potential roles in
neuropsychiatric disorders.

Liu C(1), Chung M.

Author information: 
(1)State Key Laboratory of Medical Genetics of China, Changsha, 410078, China,

Circadian rhythm alterations have been implicated in multiple neuropsychiatric
disorders, particularly those of sleep, addiction, anxiety, and mood. Circadian
rhythms are known to be maintained by a set of classic clock genes that form
complex mutual and self-regulatory loops. While many other genes showing rhythmic
expression have been identified by genome-wide studies, their roles in circadian 
regulation remain largely unknown. In attempts to directly connect circadian
rhythms with neuropsychiatric disorders, genetic studies have identified gene
mutations associated with several rare sleep disorders or sleep-related traits.
Other than that, genetic studies of circadian genes in psychiatric disorders have
had limited success. As an important mediator of environmental factors and
regulators of circadian rhythms, the epigenetic system may hold the key to the
etiology or pathology of psychiatric disorders, their subtypes or endophenotypes.
Epigenomic regulation of the circadian system and the related changes have not
been thoroughly explored in the context of neuropsychiatric disorders. We argue
for systematic investigation of the circadian system, particularly epigenetic
regulation, and its involvement in neuropsychiatric disorders to improve our
understanding of human behavior and disease etiology.

DOI: 10.1007/s12264-014-1495-3 
PMCID: PMC4821655
PMID: 25652815 


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