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Cortical thickness and the shape of psychiatric risk: a cautionary note on causality

Nature Mental Health volume 4, pages 360–361 (2026)Cite this article

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The Original Article was published on 19 May 2025

arising from B. D. Lin et al. Nature Mental Health https://doi.org/10.1038/s44220-025-00397-4 (2025)

Mendelian randomization (MR) provides powerful tools for testing potential causal relationships between cortical morphology and neuropsychiatric disorders. However, interpreting cortical thickness as a causal factor for schizophrenia requires caution. Indeed, from a developmental and transgenerational perspective, cortical morphology is not a fixed outcome, but rather a dynamic trace of complex brain– and gene–environment interactions. Therefore, causal claims may be better conceptualized in temporal, relational frameworks to reflect the deeper socio-biographical and neurodevelopmental architecture of psychiatric vulnerability.

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Author information

Authors and Affiliations

  1. Euler Institute and chair of Psychiatry, Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland

    Andrea Raballo

  2. Cantonal Sociopsychiatric Organisation, Mendrisio, Switzerland

    Andrea Raballo

  3. Department of Mental Health and Pathological Addiction, Child and Adolescent Neuropsychiatry Service, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy

    Michele Poletti

  4. Department of Neuroscience, University of Turin, Turin, Italy

    Antonio Preti

Authors
  1. Andrea Raballo
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  2. Michele Poletti
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  3. Antonio Preti
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Contributions

A.R., M.P. and A.P. equally conceived the paper and its contents. M.P. wrote the first draft. A.R. and A.P. revised the paper. All authors agreed on the final version.

Corresponding author

Correspondence to Andrea Raballo.

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The authors declare no competing interests.

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Raballo, A., Poletti, M. & Preti, A. Cortical thickness and the shape of psychiatric risk: a cautionary note on causality. Nat. Mental Health 4, 360–361 (2026). https://doi.org/10.1038/s44220-026-00602-y

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