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

Published version
Peer-reviewed

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Authors

Romero-Garcia, Rafael 
Whitaker, Kirstie J 
Morgan, Sarah E 
Fonagy, Peter 

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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Keywords

Adolescence, Allen Human Brain Atlas, Development, Fast-spiking GABAergic interneurons, Multiparameter MRI mapping, Myelination, Schizophrenia, Adolescent, Adult, Brain, Brain Mapping, Humans, Magnetic Resonance Imaging, Schizophrenia, Schizotypal Personality Disorder

Journal Title

Biol Psychiatry

Conference Name

Journal ISSN

0006-3223
1873-2402

Volume Title

88

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (095844/Z/11/Z)
Guarantors of Brain (unknown)
MQ: Transforming Mental Health (MQ17-24 Vertes)
Medical Research Council (MR/K020706/1)
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