Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Senior Researcher Armin Raznahan, NIMH - National Institute of Mental Health, US
- Second opponent: Professor Karsten Specht, University of Bergen
- Third member and chair of the evaluation committee: Professor Yvonne Böttcher, University of Oslo
Chair of the Defence
Professor Emeritus Tore Gunnar Abrahamsen, University of Oslo
Principal Supervisor
Researcher Ida Elken Sønderby, University of Oslo
Summary
Copy number variations (CNVs) are deletions or duplications of longer stretches of genetic material. Individuals carrying specific rare recurrent CNVs show altered neurodevelopment and an increased risk of developing psychiatric disorders.
The aims of this thesis were to examine the influence of rare recurrent CNVs on brain structure and to advance our understanding of the underlying neurobiology of brain structural alterations in CNV carriers. Magnetic resonance imaging-derived measures of brain structure were used to compare CNV carriers to non-carriers.
In the first study, 15q11.2 BP1-BP2 and 1q21.1 distal deletion carriers exhibited moderate to large differences, respectively, in brain structure. The brain structure in primarily frontal regions was more affected by the deletion relative to other brain regions.
In the second study, middle-to-old-aged 15q11.2 BP1-BP2 deletion or duplication carriers showed differences in brain structure, but they did not exhibit differences in estimated “brain age”, nor did they exhibit faster aging trajectories in heart, lung, and motor functioning.
In the third study, advanced neuroimaging techniques were utilized to examine the axonal density and dispersion of white matter tracts in 22q11.2 deletion carriers. 22q11.2 deletion carriers exhibited a higher axonal density and regionally variable dispersion of axons in the white matter compared to controls. In addition, patient-derived cortical spheroids revealed that the gene expression pattern of co-expressed genes differed from the control group, indicating atypical neurodevelopment at the early stages of fetal development in 22q11.2 deletion carriers.
The results of the thesis provide novel insights into how rare recurrent CNVs can influence brain structure and early gene expression levels. In the long term, these findings may help inform targeted treatments for a genetic subgroup with an increased risk of developing psychiatric disorders.
Additional information
Contact the research support staff.