Researchers highlight links and propose molecular basis investigations – ScienceDaily

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

In an article recently published in the journal Nature Translational psychiatryScientists speculate that CRD is a psychopathological factor shared by a wide range of mental illnesses and that research into its molecular basis could be the key to unlocking better therapies and treatments.

“Circadian rhythms play a vital 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 disruption of the circadian rhythm is a factor that largely overlaps the entire spectrum of mental health disorders.”

Lead author Amal Alachkar, a neuroscientist and teaching professor in the UCI Department of Pharmaceutical Sciences, noted the difficulties of testing the team’s hypothesis at the molecular level, but said the researchers found ample evidence of the connection by examining thoroughly peer-reviewed literature on the most prevalent mental disorders.

“The telltale sign of the disruption of the circadian rhythm – a problem with sleep – was present in every disorder,” Alachkar said. “Although our focus was on widely known conditions including autism, ADHD and bipolar disorder, we argue that the psychopathological factor CRD 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 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 effective and uninterrupted functioning of this natural timing system is necessary for the survival of all living organisms, according to the authors of the article.

Circadian rhythms are inherently sensitive to light / dark signals, so they can be easily interrupted by exposure to light 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 clinical effects from CRD and chronic stress.

“An interesting question that we have explored is the interaction of circadian rhythms and mental disorders with sex,” said Baldi, director of the UCI Institute of Genomics and Bioinformatics. “For example, Tourette’s syndrome occurs mainly in males and Alzheimer’s disease is more common in females at a ratio of about two-thirds to one-third.”

Age is also an important factor, according to the scientists, as CRD can affect neurological development in early childhood as well as lead to the onset of age-related mental disorders among the elderly.

Baldi said that an important unresolved question 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 UCI-led team suggests an examination of CRD at the molecular level using transcriptomic (gene expression) and metabolomic technologies in mouse models.

“This will be a high-throughput process with researchers acquiring samples from healthy and sick subjects every few hours along the circadian cycle,” Baldi said. “This approach can be applied with limitations in humans, as only serum samples can actually be used, but it could be applied on a large scale in animal models, particularly mice, by sampling tissues from different brain areas and different organs, as well as serum. . These are extensive and painstaking experiments that could benefit from having a consortium of laboratories. “

He added that if experiments were conducted systematically with respect to 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, relationships. causal and new objective and path therapies.

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

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