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

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.

Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia

“…PLSR method was used to investigate the association between spatial patterns of gene expression (of the 37 and 24 genes encompassed in the 22q11.2 and 16p11.2 genomic loci) and the 16p11.2 and 22q11.2 FC signatures. PLSR is a multivariate approach, which has previously been applied to investigate the relationship between neuroimaging phenotypes and spatial patterns of gene expression 73 – 76 . PLSR was performed separately for 16p11.2 and 22q11.2 genes.…”

Genetic, Cellular, and Connectomic Characterization of the Adult Human Brain Regions Commonly Plagued by Glioma

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Connectome Gradient Dysfunction in Major Depression and Its Association with Gene Expression Profiles

“…The fundamental architectures of functional connectomes (e.g., network hubs) are associated with gene expression profiles involving ion channel activity and oxidative metabolism 30,32 . Distinct gene expression profiles can also explain the variances in the spatial patterns of alterations in brain structures in different psychiatric states, including schizotypy 33 and autism 34 . If patients with MDD exhibit disturbances in the macroscale connectome hierarchy, we speculate that a microlevel molecular mechanism for coding these functional brain abnormalities might exist.…”