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

Romero-Garcia, R. and Seidlitz, J. and Whitaker, K.J. and Morgan, S.E. and Fonagy, P. and Dolan, R.J. and Jones, P.B. and Goodyer, I.M. and Suckling, J. and Vértes, P.E. and Bullmore, E.T. and Bullmore, E. and Dolan, R. and Goodyer, I. and Fonagy, P. and Jones, P. and Vaghi, Matilde and Moutoussis, M. and Hauser, T. and Neufeld, S. and Romero-Garcia, R. and St Clair, M. and Whitaker, K. and Inkster, B. and Prabhu, G. and Ooi, C. and Toseeb, U. and Widmer, B. and Bhatti, J. and Villis, L. and Alrumaithi, A. and Birt, S. and Bowler, A. and Cleridou, K. and Dadabhoy, H. and Davies, E. and Firkins, A. and Granville, S. and Harding, E. and Hopkins, A. and Isaacs, D. and King, J. and Kokorikou, D. and Maurice, C. and McIntosh, C. and Memarzia, J. and Mills, H. and O’Donnell, C. and Pantaleone, S. and Scott, J. and Fearon, P. and Suckling, J. and van Harmelen, A.-L. and Kievit, R. and Vértes, P. (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.

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 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.

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