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Brain micro-architecture and disinhibition: a latent phenotyping study across 33 impulsive and compulsive behaviours

Romero-Garcia, R; Hook, RW; Tiego, J; Bethlehem, RAI; Goodyer, IM; Jones, PB; Dolan, R; ... Chamberlain, SR; + view all (2020) Brain micro-architecture and disinhibition: a latent phenotyping study across 33 impulsive and compulsive behaviours. Neuropsychopharmacology 10.1038/s41386-020-00848-9. (In press). Green open access

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Abstract

Impulsive and compulsive symptoms are common, tend to co-occur, and collectively account for a substantive global disease burden. Latent phenotyping offers a promising approach to elucidate common neural mechanisms conferring vulnerability to such symptoms in the general population. We utilised the Neuroscience in Psychiatry Network (NSPN), a cohort of young people (aged 18–29 years) in the United Kingdom, who provided questionnaire data and Magnetic Resonance Imaging scans. Partial Least Squares was used to identify brain regions in which intra-cortical myelination (measured using Magnetisation Transfer, MT) was significantly associated with a disinhibition phenotype, derived from bi-factor modelling of 33 impulsive and compulsive problem behaviours. The neuroimaging sample comprised 126 participants, mean 22.8 (2.7 SD) years old, being 61.1% female. Disinhibition scores were significantly and positively associated with higher MT in the bilateral frontal and parietal lobes. 1279 genes associated with disinhibition-related brain regions were identified, which were significantly enriched for functional biological interactions reflecting receptor signalling pathways. This study indicates common microstructural brain abnormalities contributing to a multitude of related, prevalent, problem behaviours characterised by disinhibition. Such a latent phenotyping approach provides insights into common neurobiological pathways, which may help to improve disease models and treatment approaches. Now that this latent phenotyping model has been validated in a general population sample, it can be extended into patient settings.

Type: Article
Title: Brain micro-architecture and disinhibition: a latent phenotyping study across 33 impulsive and compulsive behaviours
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41386-020-00848-9
Publisher version: https://doi.org/10.1038/s41386-020-00848-9
Language: English
Additional information: 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/.
Keywords: Neuroscience, Signs and symptoms
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience
URI: https://discovery.ucl.ac.uk/id/eprint/10110523
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