Schizophrenia is a complex disease that affects up to 1% of the general population. It is manifested by a variable number of negative, positive and disorganisation symptoms giving rise to an important diversity in the expression of this syndrome. The treatment of schizophrenia is mainly based on neuroleptic drugs that alleviate, to a variable extent, psychotic symptoms in the majority but not all the patients. Although its aetiology is still unknown, it is now well established that schizophrenia is a brain disease resulting from the combination of environmental and genetic risk factors. In spite of intensive research, no specific genes were convincingly associated with schizophrenia possibly because of the presence of genetic heterogeneity. In this work, it was hypothesised that schizophrenic patients with excellent long-term response (R) and those with very poor long-term response to conventional neuroleptics (NR) may differ, at least partially, with respect to the pathogenesis of their disease. In this thesis we aimed at validating this classification scheme and illustrating its usefulness for genetic studies. In accordance with this hypothesis, it was found that NR differ from R patients with respect to age at onset, premorbid social adjustment, neuropsychological profiles and family history of psychiatric disorders. Molecular genetic investigations identified 2 genes, the hGT1 and 5-HT2a-receptor genes, that were associated respectively with responsive and nonresponsive schizophrenia, thus showing the utility of categorising patients according to their therapeutic response. A third gene, called hSWI2/SNF2 was also found to be associated with schizophrenia irrespective of therapeutic response to neuroleptics. In addition, a potentially abnormal protein was detected in two schizophrenic patients but not in controls. In conclusion, the distinction of schizophrenic patients belonging to the two extremes of long-term responsiveness to neuroleptics may help in iden
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.35930 |
| Date | January 1998 |
| Creators | Ridha, Joober. |
| Contributors | Rouleau, Guy (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Neurology and Neurosurgery.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001650667, proquestno: NQ50244, Theses scanned by UMI/ProQuest. |
Page generated in 0.0019 seconds