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Title: Sleep physiology, circadian rhythms, and the risk for developing psychosis
Author: Purple, Ross
ISNI:       0000 0004 6501 0170
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2017
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Sleep and circadian rhythm disruption (SCRD) is frequently found to co-occur in psychotic disorders. This can include a range of phenotypes such as insomnia, circadian delays, deficits in sleep spindles, and sleep-dependent cognitive impairments. However, increasing evidence suggests that psychosis occurs across a continuum of severity within the general population, yet few studies have investigated sleep and circadian rhythms prior to clinical diagnosis. Furthermore, SCRD and psychosis are posited to share underlying neuropathologies and although increasing evidence implicates shared genetic influence, little is known of the shared environmental risk. This thesis investigates sleep and circadian rhythms at multiple levels, from their occurrence in the general population, their disruption in high risk individuals, and a focus on sleep spindle oscillations in the brain. Firstly, the relationship between subjective measures of sleep and circadian rhythms, risk factors for psychosis, and psychotic-like experiences (PLEs) were studied in a large population sample. All three were highly related, with a subset of risk factors showing a strong association to both PLEs and SCRD. Secondly, sleep and circadian rhythms were assessed in individuals at high risk for developing psychosis based upon having a high load of risk factors and sub-clinical psychotic symptoms. High risk individuals showed subjective SCRD but this was not reflected in objective measures assessed by actigraphy and polysomnography. A subset of high risk individuals further showed substantially later melatonin rhythms compared to a low risk group. Thirdly, high and low risk individuals were assessed for measures of declarative and procedural sleep dependent memory consolidation. High risk individuals showed no evidence for sleep dependent cognitive impairment but did show a potential sensitivity in performance to the amount of sleep, not seen in low risk individuals. Finally, recordings in the somatosensory cortex (SCx) of mice were used as a model to explore the spatio-temporal dynamics and functional significance of sleep spindles. Distinct highly localised spindle events were discovered in the anterior SCx, with their complete absence just a fraction of a millimetre away, and their occurrence of which coincided with unique responses to global vigilance states. Together, this work pioneers research into sleep and circadian phenotypes associated with both sub-clinical psychotic symptoms and risk factors for disease and furthers our knowledge of particular sleep processes which could collectively help us to understand why SCRD and psychosis develop.
Supervisor: Wulff, Katharina ; Porcheret, Kate ; Vyazovskiy, Vladyslav Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Sleep