Schizophrenia is a genetically complex neuropsychiatric disease. Myths and uncertainty about aetiology, and concerns about familial recurrence, may contribute to the significant stigma and burden on families. There has recently been concrete progress in understanding individual
genetic causes of schizophrenia, which are now known to extend beyond 22q11.2 microdeletions to include other large rare copy number variations. However, there are limited data on issues germane to the translation of these genetic discoveries into clinical practice. The aim of this thesis was to evaluate the contemporary clinical applicability of genetic testing and genetic counselling in schizophrenia.
First, general genetic counselling was provided to both adults with schizophrenia without individually relevant genetic test results and their family members. Pre-counselling, there was evidence of widespread misconceptions about schizophrenia aetiology and familial recurrence risks, which were associated with considerable psychological distress. Post-counselling, the myriad significant lasting benefits of genetic counselling included reductions in stigma. The results provided initial evidence of need for, and efficacy of, genetic counselling for
schizophrenia.
A first ever study was then conducted of the impact of providing a specific aetiological
explanation for schizophrenia. Affected individuals and family members were found to value a molecular genetic diagnosis of a 22q11.2 microdeletion for its ability to explain the presence of stigmatized neuropsychiatric conditions. An investigation of transmission patterns and reproductive fitness associated with 22q11.2 microdeletions provided novel insights into the evolutionary biology and clinical correlates of this structural rearrangement. The results demonstrated the scientific and clinical benefits of identifying a genetic subtype of schizophrenia.
Last, high resolution genome-wide microarrays were used to investigate rare copy number variations in a prospectively recruited community-based schizophrenia cohort. Clinically significant variants were greatly enriched in schizophrenia, even with 22q11.2 microdeletions a priori excluded. The collective prevalence of these genetic variants in a single community catchment area was high, approaching that seen in autism, where clinical microarray testing is now a first-tier diagnostic test.
Collectively, the findings of these pioneering studies suggest a role for genetic testing and genetic counselling in the contemporary management of schizophrenia.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/43502 |
| Date | 07 January 2014 |
| Creators | Costain, Gregory |
| Contributors | Bassett, Anne |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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