This study explored the genetic influence of susceptibility genes on brain volumes in psychosis. More specifically, I explored whether certain allelic variations are associated with global brain volumes in subjects with psychosis, their relatives and in healthy controls. To increase the statistical power, I combined three different MRI scan datasets since a calibration study showed high intra-class correlations (ICC above 0.9) between MRI protocols (Chapter 3). I therefore included 535 participants (225 patients with psychosis, 130 relatives and 180 healthy volunteers). In the first analysis I compared grey, white and whole brain volumes between patients and healthy controls (Chapter 5). Patients with schizophrenia spectrum psychoses showed smaller grey matter and larger white matter volume, and smaller whole brain volume than healthy controls. They also showed smaller grey matter volume than patients with bipolar disorder, who also had smaller white matter volume than healthy controls. In the second analysis, I estimated differences in brain volumes between relatives and patients and healthy controls (Chapter 6). Only patients with bipolar disorder showed smaller whole brain volume than their relatives. There were no significant differences in brain volumes between the relatives of patients with bipolar disorder or schizophrenia and the healthy volunteers. Finally, I evaluated the role of familiarity on these volumes (Chapter 6). In families with schizophrenia the family clusters accounted for 48% of the total variance in grey matter volume, for 27% of the total variance in white matter volume, and for 35% of the total variance in whole brain volume. In families with bipolar disorder the family clusters accounted for 48% of the total variance in grey matter volume, for 43% of the variance in white matter volume, and 22% of the total variance in whole brain volume. In the second part of the thesis I explored genetic influence of 20 SNPs previously reported to influence brain morphometry in psychosis and in healthy individuals, on these volumes (Chapter 7). I found evidence for an association between OLIG2_rs762178, MCPH_rs930557 and DTNBP1_rs1047631 and grey, white or whole brain volumes. However, this association did not survive multiple comparison corrections. In conclusion, despite strong evidence of high heritability and familial influence on volumetric measures, I found not evidence of association between the selected candidate genes and these brain regions. These findings highlight the need to use large sample sizes when conducting this type of studies.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:628442 |
| Date | January 2014 |
| Creators | Miorelli, Ana |
| Publisher | King's College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://kclpure.kcl.ac.uk/portal/en/theses/genetic-influence-on-brain-volumes-in-psychosis(622040a1-b59c-4015-8ef4-ea28d9d9011d).html |
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