Circadian Rhythms in Mood Disorders

Circadian rhythms are endogenous, near-24-hour cycles that coordinate physiological and behavioural processes, most notably the sleep–wake cycle, hormone secretion and core body temperature. Central pacemaking arises in the suprachiasmatic nucleus, which synchronises peripheral clocks in the brain and other organs. Disruption of these rhythms—through genetic variation, environmental light exposure or altered social schedules—has been repeatedly linked to mood disorders such as major depression and bipolar disorder. Clinical profiles often include delayed or advanced sleep phase, reduced amplitude of daily activity and unstable timing of physiological markers. Such disturbances may both precipitate and perpetuate mood episodes, acting as state-dependent features during acute illness and as trait markers that confer vulnerability. An improved understanding of circadian dysregulation has given rise to chronotherapeutic interventions—light therapy, melatonin agonists and social rhythm stabilisation—and has spurred the search for objective biomarkers to guide personalised treatment.

Research from Nature Portfolio

Recent animal work has elucidated molecular links between circadian control of melatonin biosynthesis and mood-related behaviours. In a mouse model with a targeted mutation in the Asmt gene, female subjects exhibited attenuated melatonin rhythms, altered gut microbiota composition and increased anxiety- and depression-like behaviours. These findings suggest that melatonin pathway variants may affect both central clock function and peripheral homeostasis, influencing resilience to stress and the behavioural benefits of exercise. Another study applied wearable monitoring and smartphone-based mood sampling in individuals with bipolar disorder and borderline personality disorder. By fitting sinusoidal models to heart-rate and accelerometry data, researchers demonstrated that greater variability in phase and amplitude of diurnal signals correlates with fluctuations in negative and positive affect. This work underscores the potential of passive, continuous monitoring to reveal rhythm disturbances that align with mood instability and may inform targeted interventions to regularise sleep and activity patterns.

Circadian Rhythms in Mood Disorders publication trend

The graph below shows the total number of articles in circadian rhythms in mood disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Circadian rhythm: An intrinsic, approximately 24-hour cycle governing physiological and behavioural functions.

Suprachiasmatic nucleus (SCN): Hypothalamic structure serving as the master circadian pacemaker.

Amplitude: The extent of variation in a rhythmic signal, such as activity or hormone levels.

Phase: The timing of a specific point in a cycle, for example onset of melatonin secretion.

Actigraphy: Non-invasive monitoring of rest–activity cycles via a wearable sensor.

Dim light melatonin onset (DLMO): A marker of circadian phase determined by the time at which evening melatonin levels rise under dim light conditions.

References

1. Integrative Modeling of Accelerometry-Derived Sleep, Physical Activity, and Circadian Rhythm Domains With Current or Remitted Major Depression. JAMA Psychiatry (2024).
2. ASMT determines gut microbiota and increases neurobehavioral adaptability to exercise in female mice. Communications Biology (2023).
3. Manipulating the sleep-wake cycle and circadian rhythms to improve clinical management of major depression. BMC Medicine (2013).
4. Circadian rhythms and psychiatric profiles in young adults with unipolar depressive disorders. Translational Psychiatry (2018).
5. Circadian rhythmicity in emerging mood disorders: state or trait marker?. International Journal of Bipolar Disorders (2016).
6. Variability in phase and amplitude of diurnal rhythms is related to variation of mood in bipolar and borderline personality disorder. Scientific Reports (2018).
7. Insomnia, sleep loss, and circadian sleep disturbances in mood disorders: a pathway toward neurodegeneration and neuroprogression? A theoretical review. CNS Spectrums (2021).