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

Int J Mol Sci. 2017 Apr 29;18(5):938. doi: 10.3390/ijms18050938.


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.

Keywords: attention deficit hyperactivity disorder; autism spectrum disorder; circadian clocks network; circadian rhythm; clock genes; mood disorders; psychiatric disorders; schizophrenia; sleep-wake rhythm; synchronization of oscillators.

MeSH terms

  • Animals
  • Autism Spectrum Disorder / etiology
  • Autism Spectrum Disorder / genetics
  • Bipolar Disorder / etiology
  • Bipolar Disorder / genetics
  • Circadian Clocks*
  • Circadian Rhythm Signaling Peptides and Proteins / genetics*
  • Circadian Rhythm*
  • Depressive Disorder, Major / etiology
  • Depressive Disorder, Major / genetics
  • Humans
  • Mental Disorders / etiology
  • Mental Disorders / genetics*
  • Schizophrenia / etiology
  • Schizophrenia / genetics
  • Sleep Wake Disorders / etiology
  • Sleep Wake Disorders / genetics*
  • Sleep*
  • Wakefulness*


  • Circadian Rhythm Signaling Peptides and Proteins