Monocytic Subsets Impact Cerebral Cortex and Cognition: Differences Between Healthy Subjects and Patients With First-Episode Schizophrenia

Song Chen; Fengmei Fan; Fang-Ling Xuan; Ling Yan; Meihong Xiu; Hongzhen Fan; Yimin Cui; Ping Zhang; Ting Yu; Fude Yang; Baopeng Tian; L Elliot Hong; Yunlong Tan; Li Tian

doi:10.3389/fimmu.2022.900284

Monocytic Subsets Impact Cerebral Cortex and Cognition: Differences Between Healthy Subjects and Patients With First-Episode Schizophrenia

Front Immunol. 2022 Jul 11:13:900284. doi: 10.3389/fimmu.2022.900284. eCollection 2022.

Authors

Song Chen¹, Fengmei Fan¹, Fang-Ling Xuan², Ling Yan², Meihong Xiu¹, Hongzhen Fan¹, Yimin Cui³, Ping Zhang¹, Ting Yu¹, Fude Yang¹, Baopeng Tian¹, L Elliot Hong⁴, Yunlong Tan¹, Li Tian²

Affiliations

¹ Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China.
² Institute of Biomedicine and Translational Medicine, Department of Physiology, Faculty of Medicine, University of Tartu, Tartu, Estonia.
³ Department of Pharmacy, Peking University First Hospital, Beijing, China.
⁴ Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States.

Abstract

Monocytes are a highly heterogeneous population subcategorized into classical, intermediate and nonclassical subsets. How monocytes and their subsets may shape brain structures and functions in schizophrenia remains unclear. The primary goal of this cross-sectional study was to investigate monocytic subsets and their specific signature genes in regulation of cerebral cortical thickness and cognitive functions in first-episode schizophrenia (FES) patients. Whole-blood RNA sequencing of 128 FES patients and 111 healthy controls (HCs) were conducted and monocyte-specific differentially expressed genes were further analyzed. The MATRICS Consensus Cognitive Battery (MCCB) test, cortical neuroimaging and flow cytometric staining of peripheral blood monocytic subsets were performed among the participants. Significant changes in expressions of 54 monocytic signature genes were found in patients, especially for intermediate and nonclassical monocytic subsets with the most outstanding alterations being downregulated S100 Calcium Binding Protein A (S100A) and upregulated Interferon Induced Transmembrane Protein (IFITM) family members, respectively. Meanwhile, percentage of blood nonclassical monocytes was decreased in patients. Cortical thicknesses and MCCB performance were expectantly reduced and weaker intra-relationships among monocytic signature genes and cortices, respectively, were noted in patients compared to HCs. Monocytic genes were negatively associated with both cortical thicknesses and cognition in HCs, which was interestingly weakened or even reversed in patients, with nonclassical monocytic genes showing the greatest statistical significance. This study reveals that while monocytes may have negative effects on brain structure and cognition, the ameliorated phenomenon observed in schizophrenia may reflect an (mal)adaptive change of monocytes at early stage of the disorder.

Keywords: cerebral cortex; cognition; first-episode schizophrenia; immune genes; monocytes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cerebral Cortex
Cognition
Cross-Sectional Studies
Healthy Volunteers
Humans
Monocytes / metabolism
Schizophrenia* / genetics
Schizophrenia* / metabolism