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Applying dimensional psychopathology: transdiagnostic prediction of executive cognition using brain connectivity and inflammatory biomarkers

Published online by Cambridge University Press:  10 May 2022

Yange Wei ,
Fay Y. Womer ,
Kaijin Sun ,
Yue Zhu ,
Dandan Sun ,
Jia Duan ,
Ran Zhang ,
Shengnan Wei ,
Xiaowei Jiang  and
Yanbo Zhang
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Yange Wei
Affiliation:
Early Intervention Unit, Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
Fay Y. Womer
Affiliation:
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63130, USA
Kaijin Sun
Affiliation:
Early Intervention Unit, Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
Yue Zhu
Affiliation:
Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
Dandan Sun
Affiliation:
Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
Jia Duan
Affiliation:
Early Intervention Unit, Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
Ran Zhang
Affiliation:
Early Intervention Unit, Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
Shengnan Wei
Affiliation:
Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
Xiaowei Jiang
Affiliation:
Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
Yanbo Zhang
Affiliation:
Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, T6G 2B7, Canada
Yanqing Tang
Affiliation:
Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
Xizhe Zhang
Affiliation:
School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, Jiangsu 210001, China
Fei Wang*
Affiliation:
Early Intervention Unit, Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
*
Author for correspondence: Fei Wang, E-mail: fei.wang@yale.edu
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Abstract

Background

The association between executive dysfunction, brain dysconnectivity, and inflammation is a prominent feature across major psychiatric disorders (MPDs), schizophrenia, bipolar disorder, and major depressive disorder. A dimensional approach is warranted to delineate their mechanistic interplay across MPDs.

Methods

This single site study included a total of 1543 participants (1058 patients and 485 controls). In total, 1169 participants underwent diffusion tensor and resting-state functional magnetic resonance imaging (745 patients and 379 controls completed the Wisconsin Card Sorting Test). Fractional anisotropy (FA) and regional homogeneity (ReHo) assessed structural and functional connectivity, respectively. Pro-inflammatory cytokine levels [interleukin (IL)-1β, IL-6, and tumor necrosis factor-α] were obtained in 325 participants using blood samples collected with 24 h of scanning. Group differences were determined for main measures, and correlation and mediation analyses and machine learning prediction modeling were performed.

Results

Executive deficits were associated with decreased FA, increased ReHo, and elevated IL-1β and IL-6 levels across MPDs, compared to controls. FA and ReHo alterations in fronto-limbic-striatal regions contributed to executive deficits. IL-1β mediated the association between FA and cognition, and IL-6 mediated the relationship between ReHo and cognition. Executive cognition was better predicted by both brain connectivity and cytokine measures than either one alone for FA-IL-1β and ReHo-IL-6.

Conclusions

Transdiagnostic associations among brain connectivity, inflammation, and executive cognition exist across MPDs, implicating common neurobiological substrates and mechanisms for executive deficits in MPDs. Further, inflammation-related brain dysconnectivity within fronto-limbic-striatal regions may represent a transdiagnostic dimension underlying executive dysfunction that could be leveraged to advance treatment.

Keywords

Brain connectivityexecutive cognitioninflammationmachine learningmajor psychiatric disorders
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 8 , June 2023 , pp. 3557 - 3567
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Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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Footnotes

*

They are co-corresponding authors.

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