Disruption of the circadian rhythm and its possible contribution to many diseases

Circadian rhythm is the 24-hour cycle that regulates various biological processes based on the time of the day. Regulation of circadian rhythm is mediated by intrinsic sensitivity to light, coupling various bodily functions with the 24-hour cycle. Examples of processes regulated by the 24-hour cycle include hormonal production, sleep-wake cycle, and body temperature. Normal circadian rhythmicity also plays a role in neurodevelopment and cognitive function, especially in relation to gender and age. For example, estrogen and cortisol hormones modulate circadian mechanisms. Therefore, circadian rhythm dysfunction contributes to adverse neurodevelopmental and cognitive outcomes.

In their review, Alachkar et al. argue that the presence of multiple overlapping features across several mental health disorders suggests the presence of common psychopathological factors (p-factors) mediating these conditions. The authors propose that circadian rhythm disruption is one of the p-factors contributing to neurodevelopmental conditions, age-related neurodegenerative disorders, as well as adolescence and midlife psychiatric diseases.

The researchers found that the factors contributing to circadian rhythm dysfunction, like sleep disruption, are prevalent in all mental disorders at various levels, including etiological and pathophysiological mechanisms. Moreover, they highlight that the reviewed literature suggests a robust connection between circadian rhythm disruptions during pregnancy and neurodevelopmental disorders (for the offspring). They reflect upon preclinical evidence showing that maternal stressors, like psychosocial and physiological factors, influence the risk of developing neurodevelopmental diseases.

Further review and analysis of available literature revealed a link between circadian rhythm disruption and the risk of developing mental disorders during adolescence and midlife. In addition to the previous, the authors highlighted that reviewed evidence demonstrated a link between alterations in circadian rhythm coupled with decreased sleep duration and age-related neurodegenerative disorders like Alzheimer’s disease.

The authors concluded that circadian rhythm disruption, at different life stages, is involved in multiple disease conditions. They propose to consider circadian rhythm disturbance as a factor to be explored in theoretical and experimental approaches to bridge various disorders, taking into account the factors of age and gender. Also, they suggest that circadian rhythm disruption can be a generalized p-factor for mental diseases, like Parkinson’s disease, and obsessive-compulsive disorders, among others.

Source: Alachkar, A., Lee, J., Asthana, K. et al. The hidden link between circadian entropy and mental health disorders. Transl Psychiatry 12, 281 (2022). https://doi.org/10.1038/s41398-022-02028-3

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