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White matter dysfunction in psychiatric disorders is associated with neurotransmitter and genetic profiles

Nature Mental Health volume 1, pages 655–666 (2023)Cite this article

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Abstract

Functional changes of white matter are largely unexplored in patients with psychiatric disorders. This study examined white matter dysfunctions common in four major psychiatric disorders (including schizophrenia, major depressive disorder, bipolar disorder and obsessive–compulsive disorder) using multimodal magnetic resonance imaging. Here we found increased brain activity in the bilateral anterior thalamic radiation in major psychiatric disorder patients when compared with healthy controls. The spatial pattern of white matter dysfunction in patients with major psychiatric disorders was correlated with the distributions of disease-related neurotransmitters and expression maps of specific genes. These genes were enriched in excitatory neurons and ontological terms related to synaptic function. These findings were replicated in an independent dataset. Collectively, imaging dysfunction of white matter and its molecular genetic basis provided new clues to understand the pathophysiology of major psychiatric disorders.

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Fig. 1: Schematic of data generation and analysis.
Fig. 2: Dysfunctional WM tracts common to MPDs.
Fig. 3: Disorder-specific structural and functional WM changes in the discovery cohort.
Fig. 4: The WM dysfunction pattern in MPDs is associated with specific neurotransmitter profiles.
Fig. 5: Transcriptomic signatures of WM dysfunction in MPDs.
Fig. 6: Validation of WM dysfunction in MPDs.

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Data availability

Neurotransmitter receptor and transporter data can be obtained online at https://github.com/juryxy/JuSpace/tree/JuSpace_v1.5/JuSpace_v1.5/PETatlas. Human gene expression data that support the findings of this study are available in the Allen Brain Atlas (‘Complete normalized microarray datasets’, https://human.brain-map.org/static/download). A compiled cell-specific gene set list from all available large-scale single-cell studies of the adult human cortex can be obtained online at https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-020-17051-5/MediaObjects/41467_2020_170Pl51_MOESM8_ESM.xlsx. Data from the other datasets (cross-sectional datasets, SCZ, MDD, BD, OCD, HC data) are not publicly available for download, but access requests can be made to the respective study investigators: SCZ data—G.J. (jigongjun@163.com); MDD data—Y.T. (ayfytyh@126.com); BD data—L.Z. (cocozhangli@sohu.com); OCD data—C.Z. (ayswallow@126.com); HC data—K.W. (wangkai1964@126.com).

Code availability

Analyses are based on pipelines integrated within the software WhiteMatterSF toolbox (https://github.com/jigongjun/Neuroimaging-and-Neuromodulation/blob/main/WMfun/WhiteMatter.m).

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Acknowledgements

We thank the participants for taking part in this study and the Information Science Laboratory Center of USTC for the measurement services. We thank SciDraw, the open access image library, for allowing us to use their images when drafting our figure. Parts of Fig. 1 were drawn using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license. This work was supported by the National Natural Science Foundation of China, grant/award numbers 81971689 (G.J.), 31970979 (K.W.), 82090034 (K.W.), 32271134 (C.Z.), 32071054 (Y.T.) and 82001429 (T.B.); the Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health of Anhui Province, grant/award number 2020xkjT05 (K.W.); the Scientific Research Fund of Anhui Medical University, grant/award numbers 2019xkj199 (K.H.) and 2021xkj236 (L.Z.); and the key project of applied medicine research in 2021 of Hefei Municipal Health Committee, grant/award number Hwk2021zd013 (K.H.).

Author information

Author notes

  1. These authors contributed equally: Gong-Jun Ji, Jinmei Sun.

Authors and Affiliations

  1. School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China

    Gong-Jun Ji, Qiang Hua, Fengqiong Yu & Chunyan Zhu

  2. Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China

    Gong-Jun Ji, Jinmei Sun, Qiang Hua, Tongjian Bai, Ling Wei & Kai Wang

  3. Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, China

    Gong-Jun Ji, Chunyan Zhu & Kai Wang

  4. Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China

    Gong-Jun Ji, Jinmei Sun, Qiang Hua, Ting Zhang, Tongjian Bai, Ling Wei, Fengqiong Yu, Chunyan Zhu & Kai Wang

  5. Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, China

    Gong-Jun Ji, Jinmei Sun, Qiang Hua, Ting Zhang, Tongjian Bai, Ling Wei, Fengqiong Yu, Chunyan Zhu & Kai Wang

  6. Anhui Institute of Translational Medicine, Hefei, China

    Gong-Jun Ji, Fengqiong Yu, Chunyan Zhu & Kai Wang

  7. Department of Psychiatry, Fourth People’s Hospital of Hefei, Anhui Mental Health Center, Hefei, China

    Li Zhang, Anzhen Wang & Kongliang He

  8. Department of Psychiatry, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China

    Ting Zhang

  9. Center for Biomedical Engineering, University of Science and Technology of China, Hefei, China

    Xiaoxiao Wang

  10. Hefei National Laboratory for Physical Sciences at the Microscale and Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, China

    Bensheng Qiu

  11. Huaxi MR Research Center, Department of Radiology, West China Hospital of Sichuan University, Chengdu, China

    Huaiqiang Sun

  12. The Clinical Hospital of Chengdu Brain Science Institute, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China

    Wei Liao

  13. Department of Psychology and Sleep Medicine, The Second Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China

    Yanghua Tian

Authors
  1. Gong-Jun Ji
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  2. Jinmei Sun
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  3. Qiang Hua
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  4. Li Zhang
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  5. Ting Zhang
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  6. Tongjian Bai
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  7. Ling Wei
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  8. Xiaoxiao Wang
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  9. Bensheng Qiu
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  10. Anzhen Wang
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  11. Huaiqiang Sun
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  12. Wei Liao
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  13. Fengqiong Yu
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  14. Chunyan Zhu
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  15. Yanghua Tian
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  16. Kongliang He
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  17. Kai Wang
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Contributions

G.J. and J.S. designed the study, analyzed data and wrote the paper. Q.H., L.Z., T.Z., T.B., L.W. and F.Y. recruited the patients and collected clinical samples and neuroimaging data. X.W. and B.Q. assisted with imaging collection. A.W., W.L. and K.H. supervised processing and analyses of the neuroimaging data. H.S., C.Z. and Y.T. contributed to the paper. All authors evaluated the final paper. K.W. designed and supervised the study.

Corresponding author

Correspondence to Kai Wang.

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The authors declare no competing interests.

Peer review

Peer review information

Nature Mental Health thanks Shinichiro Luke Nakajima, Amanda Rodrigue and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–7, Tables 1–13, Methods and Results.

Reporting Summary

Supplementary Data

All the genes in the PLS analysis have been added in the Supplementary Gene Data.

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Ji, GJ., Sun, J., Hua, Q. et al. White matter dysfunction in psychiatric disorders is associated with neurotransmitter and genetic profiles. Nat. Mental Health 1, 655–666 (2023). https://doi.org/10.1038/s44220-023-00111-2

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