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A systematic review and meta-analysis of transdiagnostic impairments in white matter integrity across the psychosis continuum

Nature Mental Health volume 4, pages 298–306 (2026)Cite this article

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Abstract

Psychotic and mood disorders, including schizophrenia and bipolar disorder, are increasingly viewed as part of a psychosis spectrum disorder (PSD) continuum, sharing genetic and neurobiological features. This systematic review and meta-analysis examines fractional anisotropy and mean diffusivity using diffusion tensor imaging in PSD. Across 96 studies (N = 4,424 PSD, N = 5,004 controls for fractional anisotropy; N = 1,607 PSD, N = 1,709 controls for mean diffusivity), fractional anisotropy reductions were consistently observed in the corpus callosum, whereas mean diffusivity increases were found in cortico-spinal projections. Controlling for age and gender strengthened these findings, suggesting that they contribute to PSD pathophysiology rather than reflecting disease progression. Subgroup analyses revealed overlapping but distinct patterns in schizophrenia and bipolar disorder. These findings support a transdiagnostic model of psychosis, with corpus callosum abnormalities as a potential biomarker. Future longitudinal studies are needed to clarify causality and clinical implications.

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Fig. 1: Systematic search flowchart.
Fig. 2: Reduced FA, psychosis spectrum, TBSS studies only, corrected for age and gender.
Fig. 3: Increased MD, psychosis spectrum, TBSS studies only, corrected for age and gender.

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Data availability

All neuroimaging outputs (.nii.gz files and HTML reports) used in the analyses are available in Supplementary Information submitted with the paper. A summary table detailing study characteristics, methods and main findings is also included. Source data are provided with this paper.

Code availability

The SDM code is publicly accessible at https://www.sdmproject.com/.

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Acknowledgements

The preregistered protocol can be retrieved at https://osf.io/urk4y.

Author information

Author notes

  1. These authors contributed equally: Giuseppe Pierpaolo Merola, Livio Tarchi.

Authors and Affiliations

  1. Psychiatry Unit, Department of Health Sciences, University of Florence, Florence, Italy

    Giuseppe Pierpaolo Merola, Livio Tarchi, Giovanni Castellini & Valdo Ricca

  2. Psychiatry Department, Geneva University Hospital, Geneva, Switzerland

    Luigi Francesco Saccaro

  3. Faculty of Medicine, Geneva University Hospital, Switzerland, Geneva, Switzerland

    Luigi Francesco Saccaro & Camille Piguet

  4. Neuro-X Institute, École Polytechnique Fédérale de Lausanne, Geneva, Switzerland

    Luigi Francesco Saccaro, Farnaz Delavari & Dimitri Van De Ville

  5. Developmental Imaging and Psychopathology Laboratory, University of Geneva Faculty of Medicine, Geneva, Switzerland

    Farnaz Delavari

  6. General Pediatric Division, Geneva University Hospital, Geneva, Switzerland

    Camille Piguet

  7. Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland

    Dimitri Van De Ville

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Contributions

G.P.M.: conceptualization, methodology, formal analysis, investigation, writing—original draft, writing—review and editing. L.T.: conceptualization, methodology, formal analysis, validation, writing—original draft, writing—review and editing. L.F.S.: conceptualization, methodology, formal analysis, investigation, writing—original draft, writing—review and editing. F.D.: writing—review and editing. C.P.: supervision, writing—review and editing. D.V.D.V.: supervision, writing—review and editing. G.C.: supervision, writing—review and editing. V.R.: supervision, writing—review and editing.

Corresponding author

Correspondence to Luigi Francesco Saccaro.

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The authors declare no competing interests.

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Peer review information

Nature Mental Health thanks Marta Garrido and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Reporting Summary (download PDF )

Supplementary Tables 1–6 (download XLSX )

This file contains all supplementary tables: (1) Demographic and clinical characteristics (FA studies); (2) Demographic and clinical characteristics (MD studies); (3) CoCoPop (Condition, Context and Population) criteria; (4) Quality assessment; (5) Criteria quality assessment; (6) CRediT author statement.

Source data

Source Data Table 1 (download ZIP )

Blob reports for uncorrected results.

Source Data Table 2 (download ZIP )

Blob reports for FA, age- and gender-corrected results.

Source Data Table 2 (download ZIP )

Blob reports for MD, age- and gender-corrected results.

Source Data Table 3 (download ZIP )

Blob reports for results by diagnostic group, age- and gender-corrected.

Supplementary Dataset 1 (download XLSX )

Extracted data points of included studies for Fig. 1.

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Merola, G.P., Tarchi, L., Saccaro, L.F. et al. A systematic review and meta-analysis of transdiagnostic impairments in white matter integrity across the psychosis continuum. Nat. Mental Health 4, 298–306 (2026). https://doi.org/10.1038/s44220-025-00573-6

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