Thesis (M.S.)--Brock University, 2005. / Includes bibliographical references. Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (M.S.)--Brock University, 2005. / Includes bibliographical references.

The effectiveness of progressive relaxation training in decreasing the severity of neuroleptic-induced tardive dyskinesia (TD) was examined in the current study. Three residents at a county-owned nursing home who had been receiving neuroleptic medications for a number of years to treat severe mental illness participated in this study. A multiple baseline across subjects design was used to evaluate the effect of progressive relaxation training on the participant's orofacial TD symptomatology. The severity of each participant's orofacial TD was observed to improve when the intervention was introduced. Treatment integrity and IOA data that were collected indicate that the intervention was implemented at a high level of fidelity and that data were reliable. Thus, a clear functional relationship was established between progressive relaxation training and severity of orofacial TD in this study. Although the present study was preliminary in nature, the results that were obtained provide a basis upon which to develop a behavioral treatment protocol for managing TD.

Thesis (M.S.)--Brock University, 2005. / Includes bibliographical references. Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (M.S.)--Brock University, 2005. / Includes bibliographical references.

Drug-induced tardive dyskinesia, an irreversible involuntary movement disorder caused by neuroleptic drugs, may reflect cholinergic hypofunction in the corpus striatum. Therapeutic results have been reported in trials of choline and lecithin, nutritional substrates which may enhance cholinergic neurotransmission. Lecithin's effects on dyskinetic symptoms were examined in 50 male patients in a double-blind, placebo-controlled trial. Patients were randomly assigned to treatment or control groups; 31 patients were retained in the analytic cohort. Experimental patients were treated with 60 gm/day lecithin (55% phosphatidyl choline) for 11 days. Symptom frequency was rated from videotapes made at baseline, 3 and 11 days of treatment, and 1 week follow-up.

Tardive dyskinesia is an insidious and debilitating extrapyramidal side effect of neuroleptic drug treatment. Recent research has suggested that lecithin has been effective in treating tardive dyskinesia. Lecithin's effects were evaluated under double-blind placebo controlled conditions. Treatment conditions included a placebo control group, a lecithin treatment group, and a no-treatment control group. Subjects in the lecithin group received 60 gms/day of lecithin (33 gms of phosphatidylcholine) . Subjects in the placebo group received a similar mixture which contained no lecithin. Subjects received mixtures for 9-11 days. Treatment effectiveness was determined by subjective, objective, and global evaluations. All subjects were evaluated 3 to 4 days prior to treatment and following 9 to 11 days of treatment.

Schizophrenia (SCZ) is a severe neuropsychiatric disorder with a genetic component. Most candidate gene association studies have given mixed results. We investigated the GABAA receptor gamma2 subunit gene GABRG2, the dopamine receptor gene DRD3, and the Brain-derived neurotrophic factor gene BDNF that is required for D3 expression by genotyping polymorphisms spanning and surrounding these genes for association with SCZ, as well as suicidal behaviour. We also examined the BDNF, DRD3, as well as the dopamine receptor gene DRD2 and Protein Kinase B gene AKT1 for association with Tardive Dyskinesia (TD), a potentially irreversible motor side effect of long-term antipsychotic medication. Our analysis included single-marker tests, haplotype tests, and gene-gene interactions. We found a haplotype in the 5’ region of GABRG2 to be associated with SCZ in both families and matched case-control samples. We also found two synonymous DRD2 polymorphisms, rs6275 (C939T) and rs6277 (C957T), and their haplotypes, as well as a polymorphism 5’ of DRD3, rs905568, to be associated with TD. Further, we reviewed two putative functional DRD2 polymorphisms, -141C Ins/Del and TaqIA, in TD and found TaqIA 3’ of the gene to be associated with TD in a meta-analysis. Lastly, we found a significant interaction between AKT1 rs3730358 and DRD2 C939T in TD. Though replication studies are required, these results contribute to the future development of genetic tests to assess for the risks of SCZ and TD, leading to better outcome for patients suffering from these debilitating conditions.

Schizophrenia (SCZ) is a severe neuropsychiatric disorder with a genetic component. Most candidate gene association studies have given mixed results. We investigated the GABAA receptor gamma2 subunit gene GABRG2, the dopamine receptor gene DRD3, and the Brain-derived neurotrophic factor gene BDNF that is required for D3 expression by genotyping polymorphisms spanning and surrounding these genes for association with SCZ, as well as suicidal behaviour. We also examined the BDNF, DRD3, as well as the dopamine receptor gene DRD2 and Protein Kinase B gene AKT1 for association with Tardive Dyskinesia (TD), a potentially irreversible motor side effect of long-term antipsychotic medication. Our analysis included single-marker tests, haplotype tests, and gene-gene interactions. We found a haplotype in the 5’ region of GABRG2 to be associated with SCZ in both families and matched case-control samples. We also found two synonymous DRD2 polymorphisms, rs6275 (C939T) and rs6277 (C957T), and their haplotypes, as well as a polymorphism 5’ of DRD3, rs905568, to be associated with TD. Further, we reviewed two putative functional DRD2 polymorphisms, -141C Ins/Del and TaqIA, in TD and found TaqIA 3’ of the gene to be associated with TD in a meta-analysis. Lastly, we found a significant interaction between AKT1 rs3730358 and DRD2 C939T in TD. Though replication studies are required, these results contribute to the future development of genetic tests to assess for the risks of SCZ and TD, leading to better outcome for patients suffering from these debilitating conditions.

Because chronic haloperidol-treated rats demonstrate an increased incidence of spontaneous oral activity, while neonatal 6-hydroxydopamine-lesioned rats demonstrate an increased incidence of dopamine agonist-induced oral activity, we studied the influence of haloperidol in 6-hydroxydopamine-lesioned rats. At 3 days after birth rats received 6-hydroxydopamine hydrobromide (200 μg intracerebroventricularly; desipramine pretreatment, 20 mg/kg i.p., 1 h) or vehicle. Two months later haloperidol (1.5 mg/kg per day × 2 days per week, for 4 weeks; then 1.5 mg/kg per day, every day for 10 months) was added to the drinking water. After 15 weeks the level of spontaneous oral activity was stable. At 11 months there were 35.8 ± 4.9 vs. 18.4 ± 2.1 oral movements in 6-hydroxydopamine-lesioned vs. intact rats receiving haloperidol. This effect persisted unabated in lesioned rats for 4 months after haloperidol withdrawal. This stable high frequency of oral dyskinesias is an advantage for studying putative therapeutic drugs for tardive dyskinesia.