Levitis, Elizabeth;
Liu, Siyuan;
Whitman, Ethan T;
Warling, Allysa;
Torres, Erin;
Clasen, Liv S;
Lalonde, François M;
... Raznahan, Armin; + view all
(2023)
The variegation of human brain vulnerability to rare genetic disorders and convergence with behaviorally defined disorders.
Biological Psychiatry
10.1016/j.biopsych.2023.07.008.
(In press).
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Abstract
BACKGROUND: Diverse gene dosage disorders (GDDs) increase risk for psychiatric impairment, but characterization of GDD effects on the human brain has so far been piecemeal with few simultaneous analyses of multiple brain features across different GDDs. METHODS: Here, through multimodal neuroimaging of 3 aneuploidy syndromes [XXY (total n = 191, 92 controls), XYY (total n=81, 47 controls) , trisomy 21 (total n=69, 41 controls)], we systematically map the effects of supernumerary X, Y and chromosome 21 dosage across a breadth of 15 different macrostructural, microstructural, and functional imaging derived phenotypes (IDPs). RESULTS: We reveal considerable diversity in cortical changes across GDDs and IDPs. This variegation of IDP change underlines the limitations of studying GDD effects unimodally. Integration across all IDP change maps reveals highly distinct architectures of cortical change in each GDD along with partial coalescence onto a common spatial axis of cortical vulnerability that is evident in all three GDDs. This common axis shows strong alignment with shared cortical changes in behaviorally defined psychiatric disorders and is enriched for specific molecular and cellular signatures. CONCLUSION: Use of multimodal neuroimaging data in three aneuploidies indicates that different GDDs impose unique fingerprints of change in the human brain that differ widely depending on the imaging modality being considered. Embedded in this variegation is a spatial axis of shared multimodal change that aligns with shared brain changes across psychiatric disorders and therefore represents a major high-priority target for future translational research in neuroscience.
| Type: | Article |
|---|---|
| Title: | The variegation of human brain vulnerability to rare genetic disorders and convergence with behaviorally defined disorders |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.biopsych.2023.07.008 |
| Publisher version: | https://doi.org/10.1016/j.biopsych.2023.07.008 |
| Language: | English |
| Additional information: | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
| Keywords: | chromosomal aneuploidy, imaging transcriptomics, multimodal, neuroimaging, psychiatry |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10175297 |
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