Sleep and circadian rhythm disruption are frequently observed in patients with psychiatric disorders and neurodegenerative disease. The abnormal sleep that is experienced by these patients is largely assumed to be the product of medication or some other influence that is not well defined. However, normal brain function and the generation of sleep are linked by common neurotransmitter systems and regulatory pathways. Disruption of sleep alters sleep–wake timing, destabilizes physiology and promotes a range of pathologies (from cognitive to metabolic defects) that are rarely considered to be associated with abnormal sleep. We propose that brain disorders and abnormal sleep have a common mechanistic origin and that many co-morbid pathologies that are found in brain disease arise from a destabilization of sleep mechanisms. The stabilization of sleep may be a means by which to reduce the symptoms of — and permit early intervention of — psychiatric and neurodegenerative disease.
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The work is supported by the National Institute for Health Research (NIHR). Biomedical Research Centre, Oxford, UK, and The Wellcome Trust, London, UK. We would like to thank G. Goodwin (head of the Department of Psychiatry, University of Oxford, UK), C. Kennard (head of the Department of Clinical Neurology, University of Oxford, UK), K. Porcheret (Nuffield Laboratory of Ophthalmology, University of Oxford, UK), K. Davies and P. Oliver (Medical Research Council Functional Genomics Unit, University of Oxford, UK) for their valuable input during the preparation of this manuscript.
The authors declare no competing financial interests.
Supplementary information S1 (table)
Circadian/sleep-related abnormalities observed in a range of syndromes with some emerging sleep/circadian genetic associations (PDF 441 kb)
Supplementary information S2 (table)
references for Figure 3 on the health consequences of shortened/disrupted sleep and circadian rhythms. (PDF 421 kb)
- Bipolar disorder
A disorder characterized by abrupt mixed states of mood from an energetic elevated mood (termed mania or, if milder, hypomania) to a deep depressive state. Bipolar disorder type 1 classification is based on the occurrence of at least one manic episode, with or without the occurrence of a major depressive episode. Bipolar disorder type 2 is characterized by at least one hypomania episode and one major depressive state.
An individual's preference for daytime or night-time activities (also referred to as morningness and eveningness or larks and owls, respectively). Morning types wake up early and are most alert in the first part of the day, whereas evening types are most alert in the late evening hours and prefer to go to bed late.
- Circadian phase
A particular reference point in the circadian cycle. For example, the onset of sleep.
- Circadian system
(Also known as process C). The entire molecular, cellular and physiological basis for the generation of circadian rhythms in an organism.
- Diagnostic and statistical manual of mental disorders
(DSM-IV). A manual published by the American Psychiatric Association that provides diagnostic criteria for mental health disorders. DSM-IV-TR is the most recent, text-revised version published in 2000.
An activity or process that occurs during the daytime (during light).
(EEG). A measure of the electrical activity of the brain that can be used to define different wake, NREM and REM sleep states.
A special type of biomarker. In mental health, it is the division of behavioural symptoms into recognizable phenotypes with a clear genetic association.
The process by which an organism's circadian rhythm is synchronized to an environmental rhythm such as the light–dark cycle.
- Hypothalamic-pituitary-adrenal axis
A complex set of direct influences and feedback interactions among the hypothalamus, pituitary gland and adrenal glands. The hypothalamic-pituitary-adrenal (HPA) axis constitutes a major part of the neuroendocrine system that controls reactions to stress.
- International Classification of Disorders
(ICD-10). A disease classification published by the World Health Organization that provides diagnostic criteria for mental health disorders. The ICD-10 classification consists of 10 main groups.
- K complexes
A brief, negative high-voltage peak, usually greater than 100 μV. Like sleep spindles, K-complexes are another characteristic of stage two sleep.
- Light therapy
(Also known as phototherapy). Consists of exposure to daylight or artificial light (provided by a light box). Light exposure is of a defined intensity and is given at a specific time. Light therapy has been used to treat circadian rhythm disorders, such as delayed sleep phase syndrome, and can also be used to treat seasonal affective disorder.
- Major depressive disorder
A disorder characterized by severe, highly persistent depression and a loss of interest or pleasure in everyday activities. It is often associated with lack of appetite, chronic fatigue and sleep disturbances. There is an increased risk of suicide.
A chronic sleep disorder (or dyssomnia). In relation to sleep, the condition is characterized by excessive daytime sleepiness whereby the individual experiences extreme fatigue at inappropriate times and may fall asleep.
- Non-rapid eye movement sleep
(NREM). There are four distinct stages of NREM sleep (NREM 1–4) defined on the basis of EEG or polysomnography and other characteristics that are seen in each stage.
An early symptom (or set of symptoms) that might indicate the start of a disease before specific symptoms occur.
- Selective serotonin reuptake inhibitors
(Also known as serotonin-specific reuptake inhibitors). A class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders and some personality disorders. These inhibitors increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake into the presynaptic cell. This increases the level of serotonin that is available to bind to the postsynaptic receptor.
- Sleep spindles
Stage 2 sleep is characterized by sleep spindles that signify a burst of brain activity which is visible on an electroencephalogram (EEG) ranging from 11 to 16 Hz.
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Wulff, K., Gatti, S., Wettstein, J. et al. Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease. Nat Rev Neurosci 11, 589–599 (2010). https://doi.org/10.1038/nrn2868
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