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

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Romero-Garcia, Rafa 
Hook, Roxanne W 
Bethlehem, Richard AI  ORCID logo
Goodyer, Ian M 


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.



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

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Springer Science and Business Media LLC


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Wellcome Trust (110049/Z/15/Z)
Wellcome Trust (095844/Z/11/Z)
Medical Research Council (MC_G0802534)