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

Accepted version
Peer-reviewed

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Authors

Romero-Garcia, Rafa 
Hook, Roxanne W 
Bethlehem, Richard AI  ORCID logo  https://orcid.org/0000-0002-0714-0685
Goodyer, Ian M 

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.

Description

Keywords

Adolescent, Adult, Brain, Compulsive Behavior, Female, Humans, Impulsive Behavior, Magnetic Resonance Imaging, Male, Problem Behavior, United Kingdom, Young Adult

Journal Title

Neuropsychopharmacology

Conference Name

Journal ISSN

0893-133X
1740-634X

Volume Title

46

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Wellcome Trust (110049/Z/15/Z)
Wellcome Trust (095844/Z/11/Z)
Medical Research Council (MC_G0802534)