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Title: Brain and endocrine mechanisms of sleep disruption : sleep and refractory depression ; new approaches to treatment and their effect on sleep
Author: Durant, Claire Fiona
ISNI:       0000 0004 2741 3024
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2012
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Sleep disturbance is a distressing and often poorly treated core symptom of major depression. Physiological sleep abnormalities are one of the few biological markers in depression. Reported here are studies in which sleep has been used to further our understanding of two experimental treatments for patients with treatment refractory depression (TRD). The first is a crossover study of the effect of two bolus infusions of hydrocortisone administered in the afternoon on sleep that night in healthy volunteers. This study was undertaken to help interpret results in a comparable patient study, in which the effects of 3 daily, high doses of hydrocortisone on sleep were assessed on night 3 (after hydrocortisone treatment), and 4 weeks later in patients with TRD. In healthy volunteers, hydrocortisone significantly increased slow wave sleep and, in a dose dependent manner, suppressed rapid eye movement sleep (REM), despite a delay of 8-10 hours between infusion and start of sleep recordings. The low dose increased measures of arousal, resulting in delayed sleep onset. In the patient study, it was not possible to confirm any sleep effects of hydrocortisone at a group level because of low patient numbers and large baseline variations in sleep measures attributable to psychotropic medications with differing effects on sleep architecture. However, the data gave some indication that if sleep improvements were observed directly after hydrocortisone, these were sustained, although not necessarily accompanied by mood alterations. The third study was an investigation of sleep effects of deep brain stimulation (DBS) in patients with TRD. Intracerebral electrodes were implanted in the subgenual cingulate (SGC) and nucleus accumbens (NAcc) regions. Continuous stimulation was commenced in one target brain region (randomised order) which could be switched to the second if no clinical response was observed. The main finding was a striking increase in REM sleep and reduction of REM onset latency after acute SGC stimulation, but not with NAcc stimulation. These results could imply previously unknown cortical mechanisms of REM sleep modulation
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available