Robust and replicable functional brain signatures of 22q11.2 deletion syndrome and associated psychosis: a deep neural network-based multi-cohort study

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dc.contributor.authorSupekar, Kaustubh
dc.contributor.authorde los Angeles, Carlo
dc.contributor.authorRyali, Srikanth
dc.contributor.authorKushan, Leila
dc.contributor.authorSchleifer, Charlie
dc.contributor.authorRepetto, Gabriela
dc.contributor.authorCrossley, Nicolas A.
dc.contributor.authorSimon, Tony
dc.contributor.authorBearden, Carrie E.
dc.contributor.authorMenon, Vinod
dc.date.accessioned2025-01-20T17:06:17Z
dc.date.available2025-01-20T17:06:17Z
dc.date.issued2024
dc.description.abstractA major genetic risk factor for psychosis is 22q11.2 deletion (22q11.2DS). However, robust and replicable functional brain signatures of 22q11.2DS and 22q11.2DS-associated psychosis remain elusive due to small sample sizes and a focus on small single-site cohorts. Here, we identify functional brain signatures of 22q11.2DS and 22q11.2DS-associated psychosis, and their links with idiopathic early psychosis, using one of the largest multi-cohort data to date. We obtained multi-cohort clinical phenotypic and task-free fMRI data from 856 participants (101 22q11.2DS, 120 idiopathic early psychosis, 101 idiopathic autism, 123 idiopathic ADHD, and 411 healthy controls) in a case-control design. A novel spatiotemporal deep neural network (stDNN)-based analysis was applied to the multi-cohort data to identify functional brain signatures of 22q11.2DS and 22q11.2DS-associated psychosis. Next, stDNN was used to test the hypothesis that the functional brain signatures of 22q11.2DS-associated psychosis overlap with idiopathic early psychosis but not with autism and ADHD. stDNN-derived brain signatures distinguished 22q11.2DS from controls, and 22q11.2DS-associated psychosis with very high accuracies (86-94%) in the primary cohort and two fully independent cohorts without additional training. Robust distinguishing features of 22q11.2DS-associated psychosis emerged in the anterior insula node of the salience network and the striatum node of the dopaminergic reward pathway. These features also distinguished individuals with idiopathic early psychosis from controls, but not idiopathic autism or ADHD. Our results reveal that individuals with 22q11.2DS exhibit a highly distinct functional brain organization compared to controls. Additionally, the brain signatures of 22q11.2DS-associated psychosis overlap with those of idiopathic early psychosis in the salience network and dopaminergic reward pathway, providing substantial empirical support for the theoretical aberrant salience-based model of psychosis. Collectively, our findings, replicated across multiple independent cohorts, advance the understanding of 22q11.2DS and associated psychosis, underscoring the value of 22q11.2DS as a genetic model for probing the neurobiological underpinnings of psychosis and its progression.
dc.description.funderU.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
dc.fuente.origenWOS
dc.identifier.doi10.1038/s41380-024-02495-8
dc.identifier.eissn1476-5578
dc.identifier.issn1359-4184
dc.identifier.urihttps://doi.org/10.1038/s41380-024-02495-8
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/90773
dc.identifier.wosidWOS:001200393400001
dc.issue.numero10
dc.language.isoen
dc.pagina.final2966
dc.pagina.inicio2951
dc.revistaMolecular psychiatry
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleRobust and replicable functional brain signatures of 22q11.2 deletion syndrome and associated psychosis: a deep neural network-based multi-cohort study
dc.typeartículo
dc.volumen29
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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