Transcriptional and Neurochemical Signatures of Cerebral Blood Flow Alterations in Individuals With Schizophrenia or at Clinical High Risk for Psychosis

作者：Samuel Knight, Leyla Abbasova, Yashar Zeighami, Justine Y. Hansen, Daniel Martins, Fernando Zelaya, Ottavia Dipasquale, Thomas T. Liu, David Shin, Matthijs G. Bossong, Matilda Azis, Mathilde Antoniades, Oliver Howes, Ilaria Bonoldi, Alice Egerton, Paul Allen, Owen O’Daly, Philip McGuire, Gemma Modinos · 发表于：Biological Psychiatry · 年份：2025 · DOI：10.1016/j.biopsych.2025.01.028 · 被引用次数：13 · 研究领域：Tryptophan and brain disorders、Functional Brain Connectivity Studies、Schizophrenia research and treatment

Background The brain integrates multiple scales of description, from the level of cells and molecules to large-scale networks and behavior. Understanding relationships across these scales may be fundamental to advancing understanding of brain function in health and disease. Recent neuroimaging research has shown that functional brain alterations that are associated with schizophrenia spectrum disorders (SSDs) are already present in young adults at clinical high risk for psychosis (CHR-P), but the cellular and molecular determinants of these alterations remain unclear. Methods Here, we used regional cerebral blood flow (rCBF) data from 425 individuals (122 with an SSD compared with 116 healthy control participants [HCs] and 129 individuals at CHR-P compared with 58 HCs) and applied a novel pipeline to integrate brainwide rCBF case-control maps with publicly available transcriptomic data (17,205 gene maps) and neurotransmitter atlases (19 maps) from 1074 healthy volunteers. Results We identified significant correlations between astrocyte, oligodendrocyte, oligodendrocyte precursor cell, and vascular leptomeningeal cell gene modules for both SSD and CHR-P rCBF phenotypes. Additionally, endothelial cell genes were correlated in SSD, and microglia in CHR-P. Receptor distribution significantly predicted case-control rCBF differences, with dominance analysis highlighting dopamine (D 1 , D 2 , dopamine transporter), acetylcholine (VAChT, M 1 ), gamma-aminobutyric acid A (GABA A ), an...