Circadian rhythm disruption found to be common among mental health disorders

Irvine, Calif., September 1, 2022 – 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, according to a team of neuroscience researchers , Pharmaceutical and Computer Sciences from the University of California, Irvine.

In an article recently published in the journal Nature translational psychiatryScientists hypothesize that CRD is a psychopathological factor shared by a wide range of mental illnesses and that investigation of 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 the lead author. pierre baldi, Distinguished Professor of Computer Science at UCI. “Our analysis found that circadian rhythm disruption is a factor that broadly overlaps the entire spectrum of mental health disorders.”

Primary author Amal Alachkarneuroscientist and teaching professor in the UCI 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 poring over the peer-reviewed literature on disorders. most prevalent mental health

“The telltale sign of circadian rhythm disruption, a problem with sleep, was present in every disorder,” Alachkar said. “While our focus focused on well-known conditions 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, food addiction, and Parkinson’s disease.”

Circadian rhythms regulate the physiological activity and biological processes of our body during each solar day. Synchronized with 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, the maintenance of body temperature, and the consolidation of memories. The efficient and uninterrupted operation of this natural timing system is necessary for the survival of all living organisms, according to the authors of the article.

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Circadian rhythms are intrinsically sensitive to light/dark signals, so they can be easily disrupted by light exposure at night, and the level of disruption appears to be gender 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 that we explore is the interaction of circadian rhythms and mental disorders with sex,” said Baldi, director of UCI’s Institute of Genomics and Bioinformatics. “For example, Tourette’s syndrome is found primarily in men, and Alzheimer’s is about two-thirds to one-third more common in women.”

Age is also an important factor, according to the scientists, since CRD can affect neurological development in the first years of life in addition to causing the appearance of mental disorders related to aging among the elderly.

Baldi said a major 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 illnesses or a self-reinforcing symptom in disease progression?

To answer this and other questions, the UCI-led team suggests an examination of CRD at the molecular level using transcriptomics (gene expression) and metabolomics 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 mice, by sampling tissue from different areas of the brain and different organs. , in addition to whey. These are extensive and thorough experiments that could benefit from having a consortium of labs.”

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He added that if experiments were done systematically across age, gender, and brain areas to investigate circadian molecular rhythmicity before and during disease progression, it would help the mental health research community identify potential biomarkers, causal relationships, and novel therapies. goals and paths.

This project involved scientists from the UCI 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. The National Institutes of Health provided financial support.

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About the University of California, Irvine: Founded in 1965, UCI is a member of the prestigious Association of American Universities and is ranked among the top 10 public universities in the country by US News & World Report. The campus has produced five Nobel Prize winners and is known for its academic achievement, world-class research, innovation, and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 36,000 students and offers 224 degree programs. It is located in one of the safest and most economically vibrant communities in the world and is the second largest employer in Orange County, contributing $7 billion annually to the local economy and $8 billion statewide. For more information on the ICU, visit www.uci.edu.

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