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Rhythms of life: circadian disruption and brain disorders across the lifespan

Nature Reviews Neuroscience volume 20, pages 49–65 (2019)Cite this article

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Abstract

Many processes in the human body — including brain function — are regulated over the 24-hour cycle, and there are strong associations between disrupted circadian rhythms (for example, sleep–wake cycles) and disorders of the CNS. Brain disorders such as autism, depression and Parkinson disease typically develop at certain stages of life, and circadian rhythms are important during each stage of life for the regulation of processes that may influence the development of these disorders. Here, we describe circadian disruptions observed in various brain disorders throughout the human lifespan and highlight emerging evidence suggesting these disruptions affect the brain. Currently, much of the evidence linking brain disorders and circadian dysfunction is correlational, and so whether and what kind of causal relationships might exist are unclear. We therefore identify remaining questions that may direct future research towards a better understanding of the links between circadian disruption and CNS disorders.

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Fig. 1: The circadian timing system.
Fig. 2: Rhythms across the lifespan.
Fig. 3: Maternal and fetal rhythms.
Fig. 4: Effects of social constraints, sleep and circadian disruptions on adolescent brain function.
Fig. 5: Circadian regulation of dopamine.

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Acknowledgements

Figures were initially designed using BioRender software (biorender.io). Funding for the studies discussed from the authors’ group was obtained from NARSAD, International Mental Health Research Organization (IMHRO), MH106460, DA039865, DA037636, MH082876 and DA023988 to C.A.M. and from NARSAD, DA038654 and DA041872 to R.W.L.

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Nature Reviews Neuroscience thanks A. Phillips, K. Wulff and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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  1. University of Pittsburgh School of Medicine, Department of Psychiatry, Pittsburgh, PA, USA

    Ryan W. Logan & Colleen A. McClung

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  1. Ryan W. Logan
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Both authors researched data for article, made substantial contributions to the discussion of the content, wrote the article and reviewed or edited the manuscript before submission.

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Glossary

Peripheral oscillators

Circadian ‘clocks’ in other parts of the brain and in peripheral organs that are driven by the suprachiasmatic nucleus and various other nonphotic cues and stimuli.

Actigraphy

The monitoring of physical activity patterns (that is, rest–activity cycles) over many days, weeks or months, typically using non-invasive devices, such as wrist actometers.

Chronotype

The preference for early or late activities (translating to morning or evening chronotypes, respectively) during the 24-hour cycle.

Sleep homeostasis

A type of homeostasis by which prolonged periods of wakefulness lead to increases in the intensity and duration of subsequent sleep, in compensation for a sleep deficit or deprivation.

Melanopsin photoreceptors

Opsin class G protein-coupled receptors expressed in a small percentage (~2%) of photosensitive mammalian retinal ganglion cells.

Bright light therapy

A therapy for mood and sleep disorders that involves the use of bright light, typically in the morning, to shift and stabilize endogenous circadian timing.

Sleep efficiency

A measure of the integrity of sleep architecture and quality of sleep, consisting of the ratio of total sleep time to the amount of time spent in bed.

Narcolepsy

A chronic neurological disorder characterized by excessive daytime sleepiness, with many individuals experiencing intermittent, uncontrollable episodes of cataplexy (a sudden loss of muscle tone during wakefulness).

Amphetamine

A potent stimulant drug that can be used in the treatment of attention-deficit hyperactivity disorder.

Methylphenidate

A stimulant drug primarily used in the treatment of attention-deficit hyperactivity disorder.

Eveningness

The preference for activity in the evening and later bed times, related to endogenous circadian phase, and akin to evening chronotype.

Frontostriatal reward circuitry

Neural pathways that connect frontal regions with basal ganglia and mediate reward value and motivation.

Slow-wave activity

An electrophysiological measure of slow (0.5–4 Hz), synchronized oscillatory activity primarily expressed during non-rapid eye movement sleep.

Delayed sleep phase syndrome

A circadian rhythm disorder in which sleep timing is shifted later by 2 or more hours relative to normative sleep–wake cycles and often accompanied by similar shifts in body-temperature and hormone rhythms.

Acute sleep deprivation

A partial night or full night of sleep restriction. This approach can produce a short-term antidepressant effect.

Interpersonal and social rhythm therapy

A cognitive behavioural therapy often used for bipolar disorder that acts to stabilize sleep–wake and social schedules.

Dim light melatonin onset

(DLMO). A marker of endogenous circadian phase that can be used for research or to determine the appropriate timing of treatments.

Fatigue

The feeling of exhaustion and lack of energy.

REM sleep behaviour disorder

(RBD). A disorder in which there is a loss of the paralysis that normally occurs during rapid eye movement sleep, allowing the person to physically ‘act out’ their dreams.

Restless legs syndrome

A condition marked by uncomfortable sensations in the legs accompanied by the urge to move them.

MitoPark transgenic mice

A mouse model of Parkinson disease in which dopamine neurons are deficient in mitochondrial function through inactivation of mitochondrial transcription factor A.

REM sleep

A phase of sleep characterized by rapid movement of the eyes, low muscle tone and dreams that can later be recollected.

Glymphatic system

A functional waste clearance system in the brain that is active during sleep.

Astrocytosis

An abnormal increase in the number of astrocytes, attributable to the death of nearby neurons.

Mini-Mental State Examination

(MMSE). A standardized set of 11 questions with a maximal score of 30 (≤23 indicating cognitive impairment) used to assess five cognitive functional areas: orientation, registration, attention and calculation, recall and language.

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Logan, R.W., McClung, C.A. Rhythms of life: circadian disruption and brain disorders across the lifespan. Nat Rev Neurosci 20, 49–65 (2019). https://doi.org/10.1038/s41583-018-0088-y

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  • DOI: https://doi.org/10.1038/s41583-018-0088-y

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