Summary The highly overlapping nature of various characteristics in multiple mental health disorders suggests the existence of common psychopathological factors ( p-factors ) that mediate similar phenotypic presentations in distinct but identifiable disorders. In this perspective, we argue that circadian rhythm disruption (CRD) is a common underlying p-factor linking mental health disorders within their age and sex contexts. We present and analyze evidence from the literature on the critical roles that the circadian rhythm plays in regulating mental, emotional, and behavioral functions across the lifespan. A review of the literature shows that manifestations of coarse CRD, such as sleep disruption , is prevalent in all mental health disorders at the level of etiological and pathophysiological mechanisms and clinical phenotypic manifestations. Finally, we discuss the subtle interaction of CRD with sex in relation to these disorders at different stages of life. Our perspective highlights the need to shift research toward molecular levels, for example, by using spatiotemporal circadian “omics” studies in animal models to identify complex and causal relationships between CRD and mental health disorders. |
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Anxiety, autism, schizophrenia and Tourette syndrome each have their own distinctive characteristics, but one factor that unites these and most other mental disorders is circadian rhythm disruption (CRD), according to a team of researchers in neuroscience, pharmaceutical sciences, and computer science from the University of California, Irvine.
In an article recently published in the journal Nature Translational Psychiatry , scientists hypothesize that CRD is a psychopathological factor shared by a wide range of mental illnesses and that research into its molecular basis could be key to unlocking better therapies and treatments. .
"Circadian rhythms play a fundamental role in all biological systems at all scales, from molecules to populations," said senior author Pierre Baldi, UCI distinguished professor of computer science. “Our analysis found that circadian rhythm disruption is a factor that broadly overlaps across the spectrum of mental health disorders.”
Lead author Amal Alachkar, a neuroscientist and teaching professor in UCI’s Department of Pharmaceutical Sciences, noted the challenges of testing the team’s hypothesis at the molecular level, but said the researchers found ample evidence of the connection by closely examining the Peer-reviewed literature on most prevalent mental health disorders.
“The telltale sign of circadian rhythm disruption, a problem with sleep , was present in each disorder,” Alachkar said. “While our focus was on widely known conditions, such as autism, ADHD, and bipolar disorder, we argue that the psychopathology factor hypothesis of CRD can be generalized to other mental health problems, such as obsessive-compulsive disorder. , anorexia nervosa, bulimia nervosa, food addiction and Parkinson’s disease."
Circadian rhythms regulate the physiological activity and biological processes of our body during each solar day. Synchronized to a 24-hour light/dark cycle , circadian rhythms influence when we normally need to sleep and when we are awake. They also manage other functions such as the production and release of hormones, maintaining body temperature and consolidating memories. The efficient and uninterrupted operation of this natural timekeeping system is necessary for the survival of all living organisms, according to the authors of the article.
Circadian rhythms are intrinsically sensitive to light/dark cues , so they can be easily disrupted by light exposure at night, and the level of disruption appears to be sex-dependent and changes with age. An example is a hormonal response to CRD felt by pregnant women; Both mother and fetus can experience the clinical effects of CRD and chronic stress.
“An interesting topic we explored is the interaction of circadian rhythms and mental disorders with sex,” said Baldi, director of the UCI Genomics and Bioinformatics Institute. “For example, Tourette syndrome is present primarily in men, and Alzheimer’s disease is more common in women by about two-thirds to one-third.”
Age is also an important factor, according to scientists, since CRD can affect neurological development in the first years of life in addition to causing the appearance of age-related mental disorders among the elderly.
Baldi said an important unresolved issue centers on the causal relationship between CRD and mental health disorders: Is CRD a key player in the origin and onset of these diseases or a self-reinforcing symptom in disease progression?
To answer this and other questions, the team suggests examining CRD at the molecular level using transcriptomic (gene expression) and metabolomic technologies in mouse models.
“This will be a high-throughput process in which researchers will acquire samples from healthy and diseased subjects every few hours throughout the circadian cycle,” Baldi said. “This approach can be applied with limitations in humans, as only serum samples can really be used, but it could be applied on a large scale in animal models, particularly in mice, by taking tissue samples from different areas of the brain and different organs. , in addition to serum. “These are large, thorough experiments that could benefit from having a consortium of laboratories.”
He added that if experiments were conducted systematically across age, sex, and brain areas to investigate circadian molecular rhythmicity before and during disease progression, it would help the mental health research community to identify potential biomarkers, causal relationships and novel therapies. objectives and paths.
This project involved scientists from UCI’s Department of Pharmaceutical Sciences, Center for Neurobiology of Learning and Memory, Department of Computer Science, Department of Neurobiology and Behavior, and Institute of Genomics and Bioinformatics; as well as the UCLA Oppenheimer Center for the Neurobiology of Stress and Resilience and the Goodman-Luskin Microbiome Center. Financial support was provided by the National Institutes of Health.
