Clinical trajectories and genetic architecture across the neurological-psychiatric boundary
- 1Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, N
Abstract
Neurological and psychiatric disorders are treated as distinct diagnostic categories, yet genetic studies reveal substantial pleiotropy between them. Whether this overlap extends to clinical trajectories has not been tested at scale. We compared disease trajectory embeddings from Delphi-2M, a transformer model trained only on the health records of 400,000 UK Biobank participants, with genome-wide genetic correlations across 19 neurological and psychiatric disorders. Clinical and genetic similarity partly converged across disorder pairs (Mantel r = 0.33). Both measures placed most disorders closer to their own diagnostic category than to the other. Both also made the same three exceptions: multiple sclerosis, migraine, and essential tremor sat closer on average to psychiatric than to neurological disorders. Clinical trajectories and genetic architecture thus draw the same diagnostic boundary and break it in the same places. These findings support a more integrated approach to neurological and psychiatric disorders.
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BibTeX
@misc{kopal2026clinical,
title = {{Clinical trajectories and genetic architecture across the neurological-psychiatric boundary}},
author = {J. Kopal and O. B. Smeland and E. Hagen and A. Amanzadi and B. Erdos and J. Fuhrer and A. A. Shadrin and O. Frei and D. van der Meer and K. S. O'Connell and A. M. Dale and O. A. Andreassen},
howpublished = {medRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.06.26359855},
url = {https://www.medrxiv.org/content/10.64898/2026.08.06.26359855v2},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Clinical trajectories and genetic architecture across the neurological-psychiatric boundary
AU - J. Kopal
AU - O. B. Smeland
AU - E. Hagen
AU - A. Amanzadi
AU - B. Erdos
AU - J. Fuhrer
AU - A. A. Shadrin
AU - O. Frei
AU - D. van der Meer
AU - K. S. O'Connell
AU - A. M. Dale
AU - O. A. Andreassen
PY - 2026
DA - 2026/08/06
PB - medRxiv
DO - 10.64898/2026.08.06.26359855
UR - https://www.medrxiv.org/content/10.64898/2026.08.06.26359855v2
AB - Neurological and psychiatric disorders are treated as distinct diagnostic categories, yet genetic studies reveal substantial pleiotropy between them. Whether this overlap extends to clinical trajectories has not been tested at scale. We compared disease trajectory embeddings from Delphi-2M, a transformer model trained only on the health records of 400,000 UK Biobank participants, with genome-wide genetic correlations across 19 neurological and psychiatric disorders. Clinical and genetic similarity partly converged across disorder pairs (Mantel r = 0.33). Both measures placed most disorders closer to their own diagnostic category than to the other. Both also made the same three exceptions: multiple sclerosis, migraine, and essential tremor sat closer on average to psychiatric than to neurological disorders. Clinical trajectories and genetic architecture thus draw the same diagnostic boundary and break it in the same places. These findings support a more integrated approach to neurological and psychiatric disorders.
ER -