Circadian rhythm disruption is shared by a variety of mental illnesses, the study found

Circadian rhythm disruption is shared by a variety of mental illnesses, the study found

Anxiety, autism, schizophrenia and Tourette syndrome each have their own distinctive characteristics, but one factor that bridges these and most other mental disorders is circadian rhythm disruption, according to a team of neuroscience, pharmacy and computer science researchers at the University of California, Irvine.

In a recent paper published in the Nature journal Translational Psychiatry, scientists hypothesize that CRD is a psychopathological factor shared by a wide range of mental illnesses, and that exploring its molecular basis could be key to unlocking better therapies and treatments.

Circadian rhythms play a fundamental role in all biological systems at all levels, from molecules to populations. Our analysis found that circadian rhythm disruption is a factor that broadly spans the entire spectrum of mental health disorders.”

Pierre Baldi, Study Senior Author and Distinguished Professor, Computer Science, University of California – Irvine

Lead author Amal Alachkar, a neuroscientist and professor of teaching 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 thoroughly examining the peer-reviewed literature of the most common mental disorders.

“The telltale sign of a circadian rhythm disorder – a problem with sleep – was present in every disorder,” Alachkar said. "Although our focus has been on well-known disorders such as autism, ADHD and bipolar disorder, we argue that the CRD psychopathology factor hypothesis can be generalized to other mental health problems such as obsessive-compulsive disorder, anorexia nervosa, bulimia nervosa, binge eating and Parkinson's disease."

Circadian rhythms regulate our body's physiological activity and biological processes during each sunny day. Synchronized with a 24-hour light-dark cycle, the circadian rhythm influences when we normally need to sleep and when we are awake. They also manage other functions such as hormone production and release, maintaining body temperature, and consolidating memories. Effective, uninterrupted operation of this natural timekeeping system is necessary for the survival of all living organisms, according to the paper's authors.

Circadian rhythms are inherently sensitive to light/dark cues, so they can be easily disrupted by exposure to light at night, and the extent of disruption appears to be sex-dependent and change with age. An example is a hormonal response to CRD felt by pregnant women; Both the mother and the fetus can experience clinical effects of CRD and chronic stress.

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“An interesting topic we have been studying is the interaction of circadian rhythms and psychological disorders with sex,” said Baldi, director of the UCI Institute for Genomics and Bioinformatics. "For example, Tourette syndrome occurs primarily in men, and Alzheimer's disease is about two-thirds to one-third more common in women."

According to scientists, age is also an important factor as CRD can affect neurological development in early life and can also lead to the onset of age-related mental disorders in older people.

Baldi said an important unresolved issue centers on the causal relationship between CRD and mental health disorders: Is CRD a key player in the development and onset of these diseases or a self-reinforcing symptom in disease progression?

To answer these and other questions, the UCI-led team proposes to study 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 collect samples from healthy and sick subjects every few hours along the circadian cycle,” Baldi said. "This approach has limitations in humans because only serum samples can really be used, but it could be applied on a large scale in animal models, particularly mice, by additionally collecting tissue samples from different brain areas and different organs. These are large, careful experiments that could benefit from a laboratory consortium."

He added that conducting the experiments systematically across age, gender and brain areas to study circadian molecular rhythms before and during disease progression would help the mental health research community identify potential biomarkers, causal relationships and novel therapeutic targets and pathways.

This project involved scientists from the UCI Division of Pharmaceutical Sciences, the Center for the Neurobiology of Learning and Memory, the Division of Computer Science, the Division of Neurobiology and Behavior, and the Institute of Genomics and Bioinformatics; and the Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA and the Goodman-Luskin Microbiome Center. The National Institutes of Health provided financial support.

Source:

University of California – Irvine

Reference:

Alachkar, A., et al. (2022) The hidden connection between circadian entropy and mental disorders. Translational Psychiatry. doi.org/10.1038/s41398-022-02028-3.

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