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A transdiagnostic network for psychiatric illness derived from atrophy and lesions

Nature Human Behaviour volume 7, pages 420–429 (2023)Cite this article

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Abstract

Psychiatric disorders share neurobiology and frequently co-occur. This neurobiological and clinical overlap highlights opportunities for transdiagnostic treatments. In this study, we used coordinate and lesion network mapping to test for a shared brain network across psychiatric disorders. In our meta-analysis of 193 studies, atrophy coordinates across six psychiatric disorders mapped to a common brain network defined by positive connectivity to anterior cingulate and insula, and by negative connectivity to posterior parietal and lateral occipital cortex. This network was robust to leave-one-diagnosis-out cross-validation and specific to atrophy coordinates from psychiatric versus neurodegenerative disorders (72 studies). In 194 patients with penetrating head trauma, lesion damage to this network correlated with the number of post-lesion psychiatric diagnoses. Neurosurgical ablation targets for psychiatric illness (four targets) also aligned with the network. This convergent brain network for psychiatric illness may partially explain high rates of psychiatric comorbidity and could highlight neuromodulation targets for patients with more than one psychiatric disorder.

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Fig. 1: Mapping atrophy coordinates in psychiatric illness to networks rather than regions.
Fig. 2: Network mapping results align better with lesion-induced psychiatric diagnoses than traditional ALE.
Fig. 3: Convergent network topography across atrophy and brain lesions associated with psychiatric illness.
Fig. 4: Alignment between neurosurgical ablation targets for psychiatric disorders and our coordinate-based transdiagnostic network.

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Data availability

This paper used de-identified data from multiple datasets collected by different investigators at different institutions. Datasets 1 (https://doi.org/10.1001/jamapsychiatry.2014.2206), 2 (https://doi.org/10.1093/brain/awy292) and 4 (https://doi.org/10.1038/npp.2010.132) are publicly available peer-reviewed publications. Inquiries regarding the Vietnam Head Injury Study (Dataset 3) can be directed to J.G. (jgrafman@northwestern.edu). The one-sample t-test transdiagnostic network is available at https://github.com/nimlab/NHB_Taylor2023.

Code availability

GingerALE is publicly available. The custom MATLAB and Python code used in this study is available at https://github.com/nimlab/NHB_Taylor2023.

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Acknowledgements

We acknowledge the authors of Schoene-Bake et al.46, who provided us with simulated lesions from their work. We also thank W. Drew and J. Li for their technical support and P. Flynn for his administrative support. The authors received no specific funding for this work. J.J.T.: Harvard Medical School (Dupont Warren Fellowship Award and Livingston Award), Brain and Behavior Research Foundation Young Investigator Grant (no. 31081), Sidney R. Baer, Jr. Foundation, Baszucki Brain Research Fund, and the NIH (grant nos K23MH129829 and R01MH113929). C.L.: none. D.T.: NIMH T32 fellowship (no. T32MH020004) and Harvard Medical School (Dupont Warren Fellowship Award). M.A.F.: none. F.L.W.V.J.S.: Epilepsy Society (grant no. 846534). J.J.: Brain and Behavior Research Foundation Young Investigator Grant (no. 29441). M.G.: none. J.G.: none. A.E.: none. S.H.S.: NIH (grant nos K23MH121657 and R21MH126271), Brain and Behavior Research Foundation Young Investigator Grant, Neuronetics investigator-initiated grant, Baszucki Brain Research Fund, and Department of Veterans Affairs (grant no. I01CX002293). M.D.F.: the Nancy Lurie Marks Foundation, the Kaye Family Research Endowment, Baszucki Brain Research Fund and the NIH (grant nos R01MH113929, R21MH126271, R56AG069086, R01MH115949 and R01AG060987).

Author information

Author notes

  1. These authors jointly supervised this work: Shan H. Siddiqi, Michael D. Fox.

Authors and Affiliations

  1. Center for Brain Circuit Therapeutics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Joseph J. Taylor, Christopher Lin, Michael A. Ferguson, Frederic L. W. V. J. Schaper, Shan H. Siddiqi & Michael D. Fox

  2. Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Joseph J. Taylor, Shan H. Siddiqi & Michael D. Fox

  3. Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Christopher Lin, Michael A. Ferguson, Frederic L. W. V. J. Schaper & Michael D. Fox

  4. Departments of Neurology and Psychiatry, Columbia University Medical Center, Columbia University College of Physicians and Surgeons, New York, NY, USA

    Daniel Talmasov

  5. Center for the Study of World Religions, Harvard Divinity School, Cambridge, MA, USA

    Michael A. Ferguson

  6. Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA

    Jing Jiang

  7. Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA, USA

    Jing Jiang

  8. Departments of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, NM, USA

    Madeleine Goodkind

  9. New Mexico Veterans Affairs Healthcare System, Albuquerque, NM, USA

    Madeleine Goodkind

  10. Departments of Physical Medicine and Rehabilitation, Neurology, & Psychiatry, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Jordan Grafman

  11. Shirley Ryan Ability Lab, Chicago, IL, USA

    Jordan Grafman

  12. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA

    Amit Etkin

  13. Wu Tsai Neurosciences Institute at Stanford, Stanford University School of Medicine, Stanford, CA, USA

    Amit Etkin

  14. Alto Neuroscience, Los Altos, CA, USA

    Amit Etkin

Authors
  1. Joseph J. Taylor
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  2. Christopher Lin
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  3. Daniel Talmasov
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  4. Michael A. Ferguson
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  5. Frederic L. W. V. J. Schaper
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  6. Jing Jiang
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  7. Madeleine Goodkind
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  8. Jordan Grafman
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  9. Amit Etkin
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  10. Shan H. Siddiqi
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  11. Michael D. Fox
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Contributions

Conception and design of the study: J.J.T., D.T., S.H.S. and M.D.F. Design of the analytical procedures: J.J.T., F.L.W.V.J.S., M.A.F., S.H.S. and M.D.F. Preprocessing and preparation of the data for the analyses: J.J.T., C.L., D.T., M.A.F., F.L.W.V.J.S., J.J., M.G., J.G., A.E., S.H.S. and M.D.F. Neuroimaging analyses and statistical analyses: J.J.T., C.L., M.A.F., F.L.W.V.J.S., J.J., S.H.S. and M.D.F. Contribution of the data: M.G., J.G., A.E., S.H.S. and M.D.F. Interpretation of the analyses and writing of the manuscript: J.J.T., S.H.S. and M.D.F., with input from all authors.

Corresponding author

Correspondence to Joseph J. Taylor.

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Competing interests

J.J.T.: none. C.L.: none. D.T.: none. M.A.F.: none. F.L.W.V.J.S.: none. J.J.: none. M.G.: none. J.G.: none. A.E.: salary and equity from Alto Neuroscience, and equity from Mindstrong Health and Akili Interactive. S.H.S.: owner of intellectual property involving the use of brain connectivity to target TMS, scientific consultant for Magnus Medical, investigator-initiated research funding from Neuronetics and Brainsway, speaking fees from Brainsway and Otsuka (for PsychU.org), shareholder in Brainsway (publicly traded) and Magnus Medical (not publicly traded). None of these entities were directly involved in the present work. M.D.F.: scientific consultant for Magnus Medical, owner of independent intellectual property involving the use of functional connectivity to target TMS. This intellectual property was not used in the present manuscript.

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Nature Human Behaviour thanks Carissa Philippi, Ronny Redlich and Adrienne Romer for their contribution to the peer review of this work.

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Taylor, J.J., Lin, C., Talmasov, D. et al. A transdiagnostic network for psychiatric illness derived from atrophy and lesions. Nat Hum Behav 7, 420–429 (2023). https://doi.org/10.1038/s41562-022-01501-9

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