Brain micro-architecture and disinhibition: a latent phenotyping study across 33 impulsive and compulsive behaviours
Brain micro-architecture and disinhibition: a latent phenotyping study across 33 impulsive and compulsive behaviours
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.
423-431
Romero-Garcia, Rafa
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Hook, Roxanne W.
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Tiego, Jeggan
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Bethlehem, Richard A.I.
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Goodyer, Ian M.
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Jones, Peter B.
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Dolan, Ray
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Grant, Jon E.
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Bullmore, Edward T.
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Yucel, Murat
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Chamberlain, Samuel
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January 2021
Romero-Garcia, Rafa
ed2c2373-7086-4ce9-a5e5-6bda12542296
Hook, Roxanne W.
9153664e-6241-44a4-8102-769f2df97f58
Tiego, Jeggan
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Bethlehem, Richard A.I.
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Goodyer, Ian M.
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Jones, Peter B.
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Dolan, Ray
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Grant, Jon E.
07372bd5-8a0d-42b4-b41b-e376c652acf3
Bullmore, Edward T.
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Yucel, Murat
e842242b-0dd0-4b9a-b50b-0b5e2e46c2ca
Chamberlain, Samuel
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Romero-Garcia, Rafa, Hook, Roxanne W., Tiego, Jeggan, Bethlehem, Richard A.I., Goodyer, Ian M., Jones, Peter B., Dolan, Ray, Grant, Jon E., Bullmore, Edward T., Yucel, Murat and Chamberlain, Samuel
(2021)
Brain micro-architecture and disinhibition: a latent phenotyping study across 33 impulsive and compulsive behaviours.
Neuropsychopharmacology, 46 (2), .
(doi:10.1038/s41386-020-00848-9).
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.
Text
chamberlain_etal
- Accepted Manuscript
More information
Accepted/In Press date: 31 August 2020
e-pub ahead of print date: 12 September 2020
Published date: January 2021
Additional Information:
Funding Information:
This research was funded by a Clinical Fellowship from the Wellcome Trust to SRC (reference 110049/Z/15/Z & 110049/Z/15/A). The study was supported by the Neuroscience in Psychiatry Network, a strategic award from the Wellcome Trust to the University of Cambridge and University College London (095844/Z/11/Z); and by the NIHR Cambridge Biomedical Research Centre (Mental Health). R-RG was funded by Guarantors of Brain fellowship. ETB is an NIHR Senior Investigator. RAIB was funded by a British Academy Postdoctoral Fellowship. SRC consults for Promentis and Ieso Digital Health. SRC receives stipends from Elsevier from editorial work at Comprehensive Psychiatry; and at Neuroscience & Biobehavioral Reviews. JEG has received research grants from NIDA, National Center for Responsible Gaming, American Foundation for Suicide Prevention, and Forest and Roche Pharmaceuticals. JEG receives yearly compensation from Springer Publishing for acting as Editor-in-Chief of the Journal of Gambling Studies and has received royalties from Oxford University Press, American Psychiatric Publishing, Inc., Norton Press, Johns Hopkins University Press, and McGraw Hill. JT was supported by National Health and Medical Research Council (NHMRC) project grants 1050504 and 1146292. IMG consults for Lundbeck; is supported by a Wellcome Trust Strategic Award; and is Chairperson of and scientific advisor to the Peter Cundill Centre for Youth Depression Research, Centre for Addictions and Mental Health, University of Toronto. ETB is a member of the Sosei Heptares scientific advisory board and is a National Institute of Health Research Senior Investigator. MY was supported by a National Health and Medical Research Council of Australia Fellowship (#APP1117188) and the David Winston Turner Endowment Fund. The other authors report no conflicts of interest or disclosures
Publisher Copyright:
© 2020, The Author(s).
Identifiers
Local EPrints ID: 443807
URI: http://eprints.soton.ac.uk/id/eprint/443807
ISSN: 0893-133X
PURE UUID: 524efc95-57fb-49b6-a2a3-b16727505b30
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Date deposited: 14 Sep 2020 16:31
Last modified: 30 Aug 2024 04:01
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Contributors
Author:
Rafa Romero-Garcia
Author:
Roxanne W. Hook
Author:
Jeggan Tiego
Author:
Richard A.I. Bethlehem
Author:
Ian M. Goodyer
Author:
Peter B. Jones
Author:
Ray Dolan
Author:
Jon E. Grant
Author:
Edward T. Bullmore
Author:
Murat Yucel
Author:
Samuel Chamberlain
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