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.
Highlights
The impulsivity-compulsivity diathesis has been fruitful for examining a range of psychiatric disorders that are commonplace globally, as well as day-to-day behaviours
An individual with attention-deficit hyperactivity disorder (ADHD) may manifest impulsive problems such as making a statement they regret to a colleague; or jumping a red light; whereas an individual with obsessive-compulsive disorder (OCD) may repeatedly check the front door is locked, for hours per occasion
This study identified micro-structural brain changes associated with an innovative latent phenotype of disinhibition, contributing to 33 impulsive and compulsive problems, in young adults
Summary
The impulsivity-compulsivity diathesis has been fruitful for examining a range of psychiatric disorders that are commonplace globally, as well as day-to-day behaviours. An individual with attention-deficit hyperactivity disorder (ADHD) may manifest impulsive problems such as making a statement they regret to a colleague; or jumping a red light; whereas an individual with obsessive-compulsive disorder (OCD) may repeatedly (i.e. compulsively) check the front door is locked, for hours per occasion. Such symptoms lead to considerable functional impairment and burden of disease [3,4,5,6]. Impulsive and compulsive problems frequently co-occur in the same individual, and some types of disorders, such as addictions, may shift from being impulsive to compulsive over time [7], suggesting that both types of symptom are biologically related
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