UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Romero-Garacia, R; Seidlitz, J; Whitaker, KJ; Morgan, SE; Fonagy, P; Dolan, RJ; Jones, PB; ... Bullmore, ET; + view all (2020) Schizotypy-related magnetization of cortex in healthy adolescence is co-located with expression of schizophrenia-related genes. Biological Psychiatry 10.1016/j.biopsych.2019.12.005. (In press). Green open access

[thumbnail of Dolan_1-s2.0-S0006322319319225-main.pdf]
Preview
Text
Dolan_1-s2.0-S0006322319319225-main.pdf - Published Version

Download (2MB) | Preview

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.

Type: Article
Title: Schizotypy-related magnetization of cortex in healthy adolescence is co-located with expression of schizophrenia-related genes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.biopsych.2019.12.005
Publisher version: https://doi.org/10.1016/j.biopsych.2019.12.005
Language: English
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Adolescence, Allen Human Brain Atlas, Development, Fast-spiking GABAergic interneurons, Multiparameter MRI mapping, Myelination, Schizophrenia
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Clinical, Edu and Hlth Psychology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience
URI: https://discovery.ucl.ac.uk/id/eprint/10087614
Downloads since deposit
51Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item