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dc.contributor.authorMace, Janet Lee
dc.date.available2009-08-23T23:43:03Z
dc.date.copyright2007-12
dc.identifier.citationMace, J. L. (2007, December). The Effects of Acute Tryptophan Depletion on Movement, Mood, and Cognition in Patients with Parkinson’s Disease and Healthy Older Persons (Thesis, Doctor of Philosophy). University of Otago. Retrieved from http://hdl.handle.net/10523/125en
dc.identifier.urihttp://hdl.handle.net/10523/125
dc.description.abstractBackground: Serotonin (5-HT) function has been seldom investigated comprehensively in Parkinson’s disease (PD) and in healthy older persons. The response of these groups to such manipulation may differ from that of younger healthy individuals. Degeneration of the cholinergic and dopaminergic neurotransmitter systems is associated with impaired cognition and movement, especially in PD. 5-HT has a modulating role in the brain, inhibiting the activity of other neurotransmitters. Abnormalities in the serotonergic system are also linked with depression. It is possible manipulations of the serotonergic system influence different aspects of behaviour, which can be measured on a number of parameters. The technique of acute tryptophan depletion (ATD) provides a safe, temporary and replicable reduction in central 5-HT levels. It involves ingestion of a 50-100 g drink of amino acids minus tryptophan. The effect is twofold. Firstly, protein synthesis is initiated such that tryptophan circulating in the blood is incorporated into proteins and is unavailable to cross the blood brain barrier. Secondly, the large neutral amino acids out-compete tryptophan for shared transport into the brain. Objective: To investigate the effects an acute reduction in serotonin synthesis has on mood, movement and cognitive function in Parkinson’s disease and healthy older persons. Method: Three studies having double-blind, placebo-controlled, randomised, counterbalanced, crossover designs were completed. Treatment involved administration of a tryptophan depleting drink and a placebo drink. Study A comprised a new analysis of a group of 33 healthy older persons across two previous studies that used a low and a high dose of ATD. Study B compared the effects of ATD in 20 PD patients and 35 healthy matched controls. Study C examined a group of 43 healthy older persons to compare differences across those aged 50-69 years and 70-89 years. Mood and movement were assessed at baseline and at 4 and 6 hours. A large battery of behavioural and cognitive tasks, including the Modified Mini-Mental State examination (3MS), was administered between 4 and 6 hours post treatment. Results: The reduction of plasma free tryptophan after ATD was 69-71% across Studies B and C. There was no significant effect of treatment on mood, despite the number of participants being at risk for mood lowering effects of ATD. For PD patients, ATD was associated with impaired global cognitive status (3MS) and verbal memory, but improved visual memory and increased psychomotor speed; the effects in matched controls tended to be the reverse. In healthy ageing, increased age was associated with reduced psychomotor speed during ATD. Conclusion: ATD does not affect mood in PD patients or healthy older persons. However, ATD improves psychomotor speed and visual memory selectively in PD. Impairment in global cognitive status during ATD occurred selectively in PD and replicates previous work in patients with Alzheimer’s disease and recovered depression. These data suggest differing effects on aspects of neuropsychiatric function depending on the exact function being tested. Effects also depend on neuropsychiatric status, especially the degree of cholinergic deficit. The data add to evidence regarding the role of the serotonergic system in neuropsychiatric function in the elderly and in PD and may be relevant when considering potential treatments which act on the serotonergic system.en_NZ
dc.format.mimetypeapplication/pdf
dc.publisherUniversity of Otago
dc.rightshttp://www.otago.ac.nz/administration/policies/otago003228.htmlen_NZ
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.rights.urihttp://www.otago.ac.nz/administration/policies/otago003228.html
dc.subjectParkinson's diseaseen_NZ
dc.subjectMovement disordersen_NZ
dc.subjectSerotoninen_NZ
dc.subjectTryptophanen_NZ
dc.subjectdiseasesen_NZ
dc.subjectacute tryptophan depletionen_NZ
dc.subjectATDen_NZ
dc.titleThe Effects of Acute Tryptophan Depletion on Movement, Mood, and Cognition in Patients with Parkinson’s Disease and Healthy Older Personsen_NZ
dc.typeThesisen_NZ
thesis.degree.disciplineDepartment of Psychological Medicine, Christchurchen_NZ
thesis.degree.nameDoctor of Philosophyen_NZ
thesis.degree.grantorOtago Universityen_NZ
thesis.degree.levelDoctoral Thesesen_NZ
otago.openaccessOpen
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