Irvine, California, September 1, 2022 – Anxiety, autism, schizophrenia and Tourette syndrome each have their own distinguishing features, but one factor that bridges these and most other mental disorders is circadian rhythm disruption, according to a team of researchers in neuroscience, pharmaceutical science, and computer science from the University of California, Irvin.
In a recent article in the journal Nature Translational psychiatryscientists hypothesize that CRD is a psychopathological factor shared by a wide range of mental illnesses and that research into its molecular underpinnings may hold the 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 lead author Pierre Baldi, UCI Professor Emeritus of Computer Science. “Our analysis revealed that circadian rhythm disruption is a factor that broadly spans 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 many evidence of the link by extensively reviewing the peer-reviewed literature on the most common mental health disorders.
“The telltale sign of circadian rhythm disruption — a sleep problem — was present in every disorder,” Alachkar said. “While we focused on widely known conditions including autism, ADHD, and bipolar disorder, we argue that the CRD psychopathological factor hypothesis can be generalized to other mental health conditions, such as the disorder 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. According to the authors of the article, the efficient and uninterrupted functioning of this natural timing system is necessary for the survival of all living organisms.
Circadian rhythms are inherently sensitive to light/dark cues, so they can be easily disrupted by exposure to light at night, and the level of disruption appears to be gender dependent and changes with age. An example is a hormonal response to CRD experienced by pregnant women; both mother and fetus may experience the clinical effects of CRD and chronic stress.
“An interesting question we have explored 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 present primarily in men, and Alzheimer’s disease is more common in women by a ratio of about two-thirds to one-third.”
Age is also an important factor, scientists say, as CRD can affect neurological development in early life in addition to leading to the onset of age-related mental disorders in older adults.
Baldi said an important unresolved issue concerns 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 examining CRD at the molecular level using transcriptomic (gene expression) and metabolomic technologies in mouse models.
“It will be a high-throughput process with researchers acquiring samples from healthy and diseased subjects every few hours of the circadian cycle,” Baldi said. “This approach can be applied with limitations in humans, since only serum samples can actually be used, but it could be applied on a large scale in animal models, especially mice, by taking tissues from different areas brain and different organs, in addition to serum.These are deep and careful experiments that could benefit from a consortium of laboratories.
He added that if experiments were conducted in a systematic way across age, gender and brain areas to study circadian molecular rhythmicity before and during disease progression, it would help the mental health research community. to identify potential biomarkers, causal relationships and new therapeutics. targets and tracks.
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 Behaviour, 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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