Schizotypy-related magnetization of cortex in healthy adolescence is colocated with expression of schizophrenia-related genes

Romero-Garcia, Rafael, Seidlitz, Jakob, Whitaker, Kirstie J., Morgan, Sarah E., Jones, Peter B., Goodyer, Ian M., Suckling, John, Vértes, Petra E. and Bullmore, Edward T. and NSPN Consortium (2020) Schizotypy-related magnetization of cortex in healthy adolescence is colocated with expression of schizophrenia-related genes. Biological Psychiatry, 88 (3). pp. 248-259. ISSN 0006-3223

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Background: Genetic risk is thought to drive clinical variation on a spectrum of schizophrenia-like traits, but the underlying changes in brain structure that mechanistically link genomic variation to schizotypal experience and behavior are unclear. Methods: We assessed schizotypy using a self-reported questionnaire and measured magnetization transfer as a putative microstructural magnetic resonance imaging marker of intracortical myelination in 68 brain regions in 248 healthy young people (14–25 years of age). We used normative adult brain gene expression data and partial least squares analysis to find the weighted gene expression pattern that was most colocated with the cortical map of schizotypy-related magnetization. Results: Magnetization was significantly correlated with schizotypy in the bilateral posterior cingulate cortex and precuneus (and for disorganized schizotypy, also in medial prefrontal cortex; all false discovery rate–corrected ps < .05), which are regions of the default mode network specialized for social and memory functions. The genes most positively weighted on the whole-genome expression map colocated with schizotypy-related magnetization were enriched for genes that were significantly downregulated in two prior case-control histological studies of brain gene expression in schizophrenia. Conversely, the most negatively weighted genes were enriched for genes that were transcriptionally upregulated in schizophrenia. Positively weighted (downregulated) genes were enriched for neuronal, specifically interneuronal, affiliations and coded a network of proteins comprising a few highly interactive “hubs” such as parvalbumin and calmodulin. Conclusions: Microstructural magnetic resonance imaging maps of intracortical magnetization can be linked to both the behavioral traits of schizotypy and prior histological data on dysregulated gene expression in schizophrenia.

Item Type: Article
Additional Information: Funding Information: This work was supported by a strategic award from the Wellcome Trust to the University of Cambridge and University College London: the Neuroscience in Psychiatry Network (NSPN), the National Institute for Health Research Cambridge Biomedical Research Centre, the NSPN (to RR-G), the Guarantors of Brain (to RR-G), MQ fellowship Grant No. MQF17_24 (to PEV), a fellowship of the Alan Turing Institute funded under the Engineering and Physical Sciences Research Council Grant No. EP/N510129/1 (to PEV); the National Institutes of Health Oxford-Cambridge Scholars’ Program (to JS). ETB is a National Institute for Health Research Senior Investigator. We thank the Allen Brain Institute for access to human brain gene expression data, as well as all the members of the NSPN consortium for data collection, storage, and preprocessing: Edward Bullmore (Chief Investigator), Raymond Dolan, Ian Goodyer, Peter Fonagy, Peter Jones, Matilde Vaghi, Michael Moutoussis, Tobias Hauser, Sharon Neufeld, Michelle St Clair, Petra Vértes, Kirstie Whitaker, Rafael Romero-Garcia, Becky Inkster, Gita Prabhu, Cinly Ooi, Umar Toseeb, Barry Widmer, Junaid Bhatti, Laura Villis, Ayesha Alrumaithi, Sarah Birt, Aislinn Bowler, Kalia Cleridou, Hina Dadabhoy, Emma Davies, Ashlyn Firkins, Sian Granville, Elizabeth Harding, Alexandra Hopkins, Daniel Isaacs, Janchai King, Danae Kokorikou, Christina Maurice, Cleo McIntosh, Jessica Memarzia, Harriet Mills, Ciara O'Donnell, Sara Pantaleone, Jenny Scott, Pasco Fearon, Anne-Laura van Harmelen, and Rogier Kievit. This article was published as a preprint on bioRxiv: doi: The authors report no biomedical financial interests or potential conflicts of interest.
Uncontrolled Keywords: adolescence,allen human brain atlas,development,fast-spiking gabaergic interneurons,multiparameter mri mapping,myelination,schizophrenia,biological psychiatry ,/dk/atira/pure/subjectarea/asjc/2800/2803
Faculty \ School: Faculty of Social Sciences > School of Psychology
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Depositing User: LivePure Connector
Date Deposited: 04 Oct 2022 15:30
Last Modified: 03 Nov 2022 16:37
DOI: 10.1016/j.biopsych.2019.12.005


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