published_or_final_version / Pharmacology / Master / Master of Philosophy

Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Document formatted into pages; contains xxii, 200 p.; also includes graphics (some col.). Includes bibliographical references (p. 190-200). Available online via OhioLINK's ETD Center.

Thesis (M. Phil.)--University of Hong Kong, 1999. / Includes bibliographical references (leaves 86-110).

Elevated serum homocysteine concentrations are neurotoxic and are strongly implicated as a risk factor for neuropsychiatric disease (Fabender, Mielke, Bertsch, & Hennerici, 1999; Kim & Pae, 1996; Kruman et al., 2000; Reutens & Sachdev, 2002). This study compares homocysteine levels in early stages psychosis patients and healthy controls. Data from 48 healthy controls were compared with 50 previously diagnosed psychosis patients, 15-25 years, and with a gender ratio males: females 7:3. Patients were outpatients or inpatients at ORYGEN Youth Health, with a diagnosis of first episode of psychosis defined as daily psychotic symptoms lasting longer than a week that could not be explained by other means such as “drug-induced” or “organic”. / All subjects were interviewed to collect information relating to family psychotic history. A possible history of psychotic disease in control subjects was tested using the SCID Psych Screening Module, drug use recorded using Alcohol Use Disorders Identification Test (AUDIT) (for alcohol use), The Modified Fagerström Tolerance Questionnaire (mFTQ) (for smoking), Opiate Treatment Index (OTI) (for opiate-type drugs). Dietary and medication histories were also taken. Blood tests were performed to determine serum homocysteine, serum folate, red blood cell folate and serum vitamin B12 levels. / An independent sample t test to compare homocysteine levels in patients and controls was performed. Serum homocysteine levels were significantly higher for patients (M = 12.9, S.D. = 3.6) than controls (M = 11.1, S.D. = 2.7) (t(96) = 2.7, p = 0.007, two-tailed). After General Linear Model (GLM) analysis it was found that group (patients or controls), and not serum folate, vitamin B12 and the T allele of MTHFR C677 polymorphism had significant effect on homocysteine levels. Thus a number of factors that may increase homocysteine levels were ruled out. / Although it was not possible to obtain a complete data set for some factors (alcohol, smoking and caffeine consumption) (a weakness of the study), strengths included consecutive recruitment, minimisation of selection bias, good matching for age and gender between patients and controls, and the consideration of (serum) folate and (serum) vitamin B12 as potential confounding variables. / A number of other studies have found significantly increased homocysteine levels in young patients compared with controls, particularly males. Most related studies favoured the homocysteine-psychosis link. / The probability of symptomatic recovery is very high (80-90%) after treatment for first episode psychosis (Robinson et al., 1999) and delayed treatment, but prolonged duration of treatment is associated with poorer response in treatment and worse outcome (Malla & Norman, 2002). This justifies studying homocysteine levels and cognitive function in that first period of psychosis. / This research offers evidence for the importance of serum homocysteine levels as showing involvement in the etiology of psychosis. Lowering homocysteine may have a beneficial effect on symptoms and cognitive dysfunction in psychotic illness. / Two randomised controlled trials have demonstrated benefit in psychotic illness of giving folate and consequently reducing homocysteine.(Godfrey & Toone, 1990; Levine et al., 2006b). Benefits of taking folate were found in both trials for both cognition and psychotic symptoms. By reducing homocysteine levels early in the illness, some of the excess cardiovascular mortality may be prevented. / Secondary prevention of CVD does not appear to influence outcome (Hermann, Herrmann, & Obeid, 2007), so the right time to intervene and reduce risk would appear to be early in the course of psychosis. Additionally, by lowering homocysteine cognitive functioning and psychotic symptoms may be improved (Levine et al., 2006b).

Homocysteine (Hcy) is metabolized through a series of remethylation and transsulphuration processes that require the co-factors vitamins B6, folate (the nutrient derived from food, and folic acid is supplemental), and B12. Homocysteine metabolism results in the production of creatine (Cr). By way of negative feedback creatine supplements could potentially decrease Hcy production. Low dietary intake of vitamins and creatine, often a consequence of a vegetarian diet may also increase serum Hcy concentrations. It was therefore the purpose of this study to examine the effect of a five day creatine loading period (0.25 g Cr/kg lean body mass (LBM)/day) in female vegetarians (VG) (n=9, age 25 ± 3.6) and non-vegetarians (NV) (n=11, age 24 ± 5.9) on serum levels of Hcy, vitamins B6 and B12, whole blood folate, and on a number of fitness measures known to be positively affected by creatine supplementation: peak torque and average power during leg extensions; one repetition maximum (1RM) bench and leg press; peak power during repeated Wingate anaerobic tests. Aside from a difference in change scores for leg press, there were no differences between dietary groups for the fitness measures, and therefore the participants were pooled for comparisons between time points. Urinary creatine was significantly greater following the five day loading period (81 ± 113 vs. 647 ± 421 µmol). In contrast, urinary creatinine did not change. A significant increase in plasma vitamin B6 (pyridoxal 5-phosphate) was found (72 ± 24 vs. 94 ± 24 nmol/L) (p < 0.05), although there were no between group differences. Serum Hcy, vitamin B12, and whole blood folate levels did not change significantly over time in either group. Participants showed significant increases post-loading in bench press (45 ± 13 vs. 48 ± 12 kg.) and leg press (116 ± 35 vs. 125 ± 40 kg) (p < 0.05). Changes scores for leg press were greater for the vegetarian participants when compared with non-vegetarians (16 ± 16 vs. 3 ± 9 kg). Significant improvements post-loading were also noted for peak torque (85.0 ± 15.0 vs. 91.8 ± 12.9 Nm) and average power (99.5 ± 14.4 vs. 107.1 ± 14.8 W) (p < 0.05). Peak power during repeated Wingate anaerobic tests also significantly improved in response to the intervention (449.2 ± 92.6 vs. 472.4 ± 103.5 W) (p < 0.05). This response did not differ however between the two diet groups. These results suggest that a five day creatine loading protocol similarly affects fitness performance measures in both vegetarians and non-vegetarians. There was no significant effect of the supplementation protocol on serum Hcy concentration, suggesting that the supplemented creatine did not decrease the reformation of Hcy, as originally hypothesized.

Homocysteine (Hcy) is metabolized through a series of remethylation and transsulphuration processes that require the co-factors vitamins B6, folate (the nutrient derived from food, and folic acid is supplemental), and B12. Homocysteine metabolism results in the production of creatine (Cr). By way of negative feedback creatine supplements could potentially decrease Hcy production. Low dietary intake of vitamins and creatine, often a consequence of a vegetarian diet may also increase serum Hcy concentrations. It was therefore the purpose of this study to examine the effect of a five day creatine loading period (0.25 g Cr/kg lean body mass (LBM)/day) in female vegetarians (VG) (n=9, age 25 ± 3.6) and non-vegetarians (NV) (n=11, age 24 ± 5.9) on serum levels of Hcy, vitamins B6 and B12, whole blood folate, and on a number of fitness measures known to be positively affected by creatine supplementation: peak torque and average power during leg extensions; one repetition maximum (1RM) bench and leg press; peak power during repeated Wingate anaerobic tests. Aside from a difference in change scores for leg press, there were no differences between dietary groups for the fitness measures, and therefore the participants were pooled for comparisons between time points. Urinary creatine was significantly greater following the five day loading period (81 ± 113 vs. 647 ± 421 µmol). In contrast, urinary creatinine did not change. A significant increase in plasma vitamin B6 (pyridoxal 5-phosphate) was found (72 ± 24 vs. 94 ± 24 nmol/L) (p < 0.05), although there were no between group differences. Serum Hcy, vitamin B12, and whole blood folate levels did not change significantly over time in either group. Participants showed significant increases post-loading in bench press (45 ± 13 vs. 48 ± 12 kg.) and leg press (116 ± 35 vs. 125 ± 40 kg) (p < 0.05). Changes scores for leg press were greater for the vegetarian participants when compared with non-vegetarians (16 ± 16 vs. 3 ± 9 kg). Significant improvements post-loading were also noted for peak torque (85.0 ± 15.0 vs. 91.8 ± 12.9 Nm) and average power (99.5 ± 14.4 vs. 107.1 ± 14.8 W) (p < 0.05). Peak power during repeated Wingate anaerobic tests also significantly improved in response to the intervention (449.2 ± 92.6 vs. 472.4 ± 103.5 W) (p < 0.05). This response did not differ however between the two diet groups. These results suggest that a five day creatine loading protocol similarly affects fitness performance measures in both vegetarians and non-vegetarians. There was no significant effect of the supplementation protocol on serum Hcy concentration, suggesting that the supplemented creatine did not decrease the reformation of Hcy, as originally hypothesized.

Thesis (M. Med. Sc.)--University of Hong Kong, 2001. / Includes bibliographical references.

Thesis (Ph.D.)--Memorial University of Newfoundland, 2002. / Bibliography: leaves 183-218.

Thesis (M. Phil.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 80-110).

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy