Abstract
Objective: Individuals carrying rare, but biologically informative genetic variants provide a unique opportunity to model major mental illness and inform understanding of disease mechanisms. The rarity of such variations means that their study involves small group numbers, however they are amongst the strongest known genetic risk factors for major mental illness and are likely to have large neural effects. DISC1 (Disrupted in Schizophrenia 1) is a gene containing one such risk variant, identified in a single Scottish family through its disruption by a balanced translocation of chromosomes 1 and 11; t(1;11) (q42.1;q14.3).
Method: Within the original pedigree, we examined the effects of the t(1;11) translocation on white matter integrity, measured by fractional anisotropy (FA). This included family members with (n = 7) and without (n = 13) the translocation, along with a clinical control sample of patients with psychosis (n = 34), and a group of healthy controls (n = 33).
Results: We report decreased white matter integrity in five clusters in the genu of the corpus callosum, the right inferior fronto-occipital fasciculus, acoustic radiation and fornix. Analysis of the mixed psychosis group also demonstrated decreased white matter integrity in the above regions. FA values within the corpus callosum correlated significantly with positive psychotic symptom severity.
Conclusions: We demonstrate that the t(1;11) translocation is associated with reduced white matter integrity in frontal commissural and association fibre tracts. These findings overlap with those shown in affected patients with psychosis and in DISC1 animal models and highlight the value of rare but biologically informative mutations in modeling psychosis.
| Original language | English |
|---|---|
| Article number | e0130900 |
| Journal | PLoS ONE |
| Volume | 10 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 23 Jun 2015 |
Bibliographical note
Funding Information:We would like to thank all of the participants who took part in the study and the radiographers who acquired the MRI scans. This study was conducted at the Clinical Research Imaging Centre ( http://www.cric.ed.ac.uk ), University of Edinburgh. We are also grateful to Edwin van Beek for assistance with overall co-ordination of the study and examining the structural MRI scans of all participants to exclude gross lesions. The investigators also acknowledge the financial support of National Health Service (NHS) Research Scotland, through the Scottish Mental Health Research Network ( http://www.smhrn.org.uk ) who provided assistance with subject recruitment and cognitive assessments. The authors would also like to thank Dr. Thorsten Feiweier from Siemens Healthcare for providing the prototype diffusion sequence used in this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Publisher Copyright:
© 2015 Whalley et al.
ASJC Scopus subject areas
- General
