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Schizotypy-Related Magnetization of Cortex in Healthy Adolescence Is Colocated With Expression of Schizophrenia-Related Genes

Authors
  • Romero-Garcia, Rafael1
  • Seidlitz, Jakob1
  • Whitaker, Kirstie J.1, 2
  • Morgan, Sarah E.1
  • Fonagy, Peter3
  • Dolan, Raymond J.4, 5
  • Jones, Peter B.1, 6
  • Goodyer, Ian M.1, 6
  • Suckling, John1
  • Bullmore, Edward
  • Dolan, Raymond
  • Goodyer, Ian
  • Fonagy, Peter
  • Jones, Peter
  • Vaghi, Matilde
  • Moutoussis, Michael
  • Hauser, Tobias
  • Neufeld, Sharon
  • Romero-Garcia, Rafael
  • St Clair, Michelle
  • And 33 more
  • 1 Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
  • 2 Alan Turing Institute, London, United Kingdom
  • 3 Research Department of Clinical, Educational and Health Psychology, London, United Kingdom
  • 4 Max Planck UCL Centre for Computational Psychiatry and Ageing Research, University College London, London, United Kingdom
  • 5 Wellcome Trust Centre for Neuroimaging, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
  • 6 Cambridgeshire and Peterborough NHS Foundation Trust, Huntingdon, United Kingdom
Type
Published Article
Publication Date
Aug 01, 2020
Volume
88
Issue
3
Pages
248–259
Identifiers
DOI: 10.1016/j.biopsych.2019.12.005
PMID: 32029217
PMCID: PMC7369635
Source
PubMed Central
Keywords
License
Unknown

Abstract

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 p s  <  .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.

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