Skip to navigation Skip to main content Skip to footer

Approved Research

Relationship between the Circadian System and Major Depressive Disorder using Mendelian Randomisation

Principal Investigator: Ms Valentina Paz
Approved Research ID: 68232
Approval date: April 20th 2021

Lay summary

Daily rhythms of different bodily functions are regulated by the Circadian System (CS). In humans, the presence of these rhythms is evidenced, for example, in the sleep-wake cycle.

Desynchronization of this system has been linked to various diseases, including Major Depressive Disorder (MDD). MDD is a highly prevalent disorder, ranked as the leading cause of disability worldwide. MD strongly affects quality of life and causes big economic costs to society. However, the association between the CS and MDD is still unclear and as correlation does not necessarily imply causation, it is still unknown whether MDD causes changes in the CS and/or changes in the CS lead to the development of MDD.

Over a two-year period, we aim to investigate whether there is a causal association between circadian system disturbances and MDD. We hope that a deeper understanding of the relationship between the CS and MDD will further our knowledge of this disorder and contribute to the development of more effective prevention, diagnosis, and treatment strategies.

Scope extension:

In recent years, there has been a growing interest in the relationship between the Circadian System (CS) and the onset, course, and treatment of Major Depressive Disorder (MDD). This interest has arisen from multiple studies that show a clear association between CS and MDD, even postulating that changes in sleep patterns or evening circadian preferences may be risk factors for its development. However, it is still unclear whether MDD causes changes in the CS and/or if these changes lead to the development of this disorder. For this reason, the present study aims to investigate whether there is a causal association between alterations in CS and MDD using Mendelian Randomisation.

Mounting evidence has revealed a shared aetiology and comorbid expression across the mental health spectrum. Notwithstanding the distinct diagnostic classifications between common and severe mental conditions, there are noteworthy conceptual, clinical, and causal links that should prevent entirely discrete lines of study. Clear also is that mental illness is biologically complex, driven by a network of interdependent mechanisms. Sleep has been identified as a germane antecedent of interest across experimental and epidemiological paradigms. Noted for its homeostatic role in the regulation of inflammatory processes that are implicated in the aetiopathogenesis of a number of mental illnesses. We therefore seek to determine whether sleep duration has a causal effect on mental illness across a spectrum of severity, and whether low-grade systemic inflammatory processes mediate associations.