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Transdiagnostic dimensions of psychopathology explain individuals’ unique deviations from normative neurodevelopment in brain structure

Psychopathology is rooted in neurodevelopment. However, clinical and biological heterogeneity, together with a focus on case-control approaches, have made it difficult to link dimensions of psychopathology to abnormalities of neurodevelopment. Here, using the Philadelphia Neurodevelopmental Cohort,...

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Autores principales: Parkes, Linden, Moore, Tyler M., Calkins, Monica E., Cook, Philip A., Cieslak, Matthew, Roalf, David R., Wolf, Daniel H., Gur, Ruben C., Gur, Raquel E., Satterthwaite, Theodore D., Bassett, Danielle S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058055/
https://www.ncbi.nlm.nih.gov/pubmed/33879764
http://dx.doi.org/10.1038/s41398-021-01342-6
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author Parkes, Linden
Moore, Tyler M.
Calkins, Monica E.
Cook, Philip A.
Cieslak, Matthew
Roalf, David R.
Wolf, Daniel H.
Gur, Ruben C.
Gur, Raquel E.
Satterthwaite, Theodore D.
Bassett, Danielle S.
author_facet Parkes, Linden
Moore, Tyler M.
Calkins, Monica E.
Cook, Philip A.
Cieslak, Matthew
Roalf, David R.
Wolf, Daniel H.
Gur, Ruben C.
Gur, Raquel E.
Satterthwaite, Theodore D.
Bassett, Danielle S.
author_sort Parkes, Linden
collection PubMed
description Psychopathology is rooted in neurodevelopment. However, clinical and biological heterogeneity, together with a focus on case-control approaches, have made it difficult to link dimensions of psychopathology to abnormalities of neurodevelopment. Here, using the Philadelphia Neurodevelopmental Cohort, we built normative models of cortical volume and tested whether deviations from these models better predicted psychiatric symptoms compared to raw cortical volume. Specifically, drawing on the p-factor hypothesis, we distilled 117 clinical symptom measures into six orthogonal psychopathology dimensions: overall psychopathology, anxious-misery, externalizing disorders, fear, positive psychosis symptoms, and negative psychosis symptoms. We found that multivariate patterns of deviations yielded improved out-of-sample prediction of psychopathology dimensions compared to multivariate patterns of raw cortical volume. We also found that correlations between overall psychopathology and deviations in ventromedial prefrontal, inferior temporal, and dorsal anterior cingulate cortices were stronger than those observed for specific dimensions of psychopathology (e.g., anxious-misery). Notably, these same regions are consistently implicated in a range of putatively distinct disorders. Finally, we performed conventional case-control comparisons of deviations in a group of individuals with depression and a group with attention-deficit hyperactivity disorder (ADHD). We observed spatially overlapping effects between these groups that diminished when controlling for overall psychopathology. Together, our results suggest that modeling cortical brain features as deviations from normative neurodevelopment improves prediction of psychiatric symptoms in out-of-sample testing, and that p-factor models of psychopathology may assist in separating biomarkers that are disorder-general from those that are disorder-specific.
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spelling pubmed-80580552021-05-05 Transdiagnostic dimensions of psychopathology explain individuals’ unique deviations from normative neurodevelopment in brain structure Parkes, Linden Moore, Tyler M. Calkins, Monica E. Cook, Philip A. Cieslak, Matthew Roalf, David R. Wolf, Daniel H. Gur, Ruben C. Gur, Raquel E. Satterthwaite, Theodore D. Bassett, Danielle S. Transl Psychiatry Article Psychopathology is rooted in neurodevelopment. However, clinical and biological heterogeneity, together with a focus on case-control approaches, have made it difficult to link dimensions of psychopathology to abnormalities of neurodevelopment. Here, using the Philadelphia Neurodevelopmental Cohort, we built normative models of cortical volume and tested whether deviations from these models better predicted psychiatric symptoms compared to raw cortical volume. Specifically, drawing on the p-factor hypothesis, we distilled 117 clinical symptom measures into six orthogonal psychopathology dimensions: overall psychopathology, anxious-misery, externalizing disorders, fear, positive psychosis symptoms, and negative psychosis symptoms. We found that multivariate patterns of deviations yielded improved out-of-sample prediction of psychopathology dimensions compared to multivariate patterns of raw cortical volume. We also found that correlations between overall psychopathology and deviations in ventromedial prefrontal, inferior temporal, and dorsal anterior cingulate cortices were stronger than those observed for specific dimensions of psychopathology (e.g., anxious-misery). Notably, these same regions are consistently implicated in a range of putatively distinct disorders. Finally, we performed conventional case-control comparisons of deviations in a group of individuals with depression and a group with attention-deficit hyperactivity disorder (ADHD). We observed spatially overlapping effects between these groups that diminished when controlling for overall psychopathology. Together, our results suggest that modeling cortical brain features as deviations from normative neurodevelopment improves prediction of psychiatric symptoms in out-of-sample testing, and that p-factor models of psychopathology may assist in separating biomarkers that are disorder-general from those that are disorder-specific. Nature Publishing Group UK 2021-04-20 /pmc/articles/PMC8058055/ /pubmed/33879764 http://dx.doi.org/10.1038/s41398-021-01342-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Parkes, Linden
Moore, Tyler M.
Calkins, Monica E.
Cook, Philip A.
Cieslak, Matthew
Roalf, David R.
Wolf, Daniel H.
Gur, Ruben C.
Gur, Raquel E.
Satterthwaite, Theodore D.
Bassett, Danielle S.
Transdiagnostic dimensions of psychopathology explain individuals’ unique deviations from normative neurodevelopment in brain structure
title Transdiagnostic dimensions of psychopathology explain individuals’ unique deviations from normative neurodevelopment in brain structure
title_full Transdiagnostic dimensions of psychopathology explain individuals’ unique deviations from normative neurodevelopment in brain structure
title_fullStr Transdiagnostic dimensions of psychopathology explain individuals’ unique deviations from normative neurodevelopment in brain structure
title_full_unstemmed Transdiagnostic dimensions of psychopathology explain individuals’ unique deviations from normative neurodevelopment in brain structure
title_short Transdiagnostic dimensions of psychopathology explain individuals’ unique deviations from normative neurodevelopment in brain structure
title_sort transdiagnostic dimensions of psychopathology explain individuals’ unique deviations from normative neurodevelopment in brain structure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058055/
https://www.ncbi.nlm.nih.gov/pubmed/33879764
http://dx.doi.org/10.1038/s41398-021-01342-6
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