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Transdiagnostic variations in impulsivity and compulsivity in obsessive-compulsive disorder and gambling disorder correlate with effective connectivity in cortical-striatal-thalamic-cortical circuits.

Accepted version
Peer-reviewed

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Article

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Authors

Parkes, Linden 
Tiego, Jeggan 
Aquino, Kevin 
Braganza, Leah 
Chamberlain, Samuel R 

Abstract

Individual differences in impulsivity and compulsivity is thought to underlie vulnerability to a broad range of disorders and are closely tied to cortical-striatal-thalamic-cortical function. However, whether impulsivity and compulsivity in clinical disorders is continuous with the healthy population and explains cortical-striatal-thalamic-cortical dysfunction across different disorders remains unclear. Here, we characterized the relationship between cortical-striatal-thalamic-cortical effective connectivity, estimated using dynamic causal modelling of resting-state functional magnetic resonance imaging data, and dimensional phenotypes of impulsivity and compulsivity in two symptomatically distinct but phenotypically related disorders, obsessive-compulsive disorder and gambling disorder. 487 online participants provided data for modelling of dimensional phenotypes. These data were combined with 34 obsessive-compulsive disorder patients, 22 gambling disorder patients, and 39 healthy controls, who underwent functional magnetic resonance imaging. Three core dimensions were identified: disinhibition, impulsivity, and compulsivity. Patients' scores on these dimensions were continuously distributed with the healthy participants, supporting a continuum model of psychopathology. Across all participants, higher disinhibition correlated with lower bottom-up connectivity in the dorsal circuit and greater bottom-up connectivity in the ventral circuit, and higher compulsivity correlated with lower bottom-up connectivity in the dorsal circuit. In patients, higher clinical severity was also linked to lower bottom-up connectivity in the dorsal circuit, but these findings were independent of phenotypic variation, demonstrating convergence towards behaviourally and clinically relevant changes in brain dynamics. Effective connectivity did not differ as a function of traditional diagnostic labels and only weak associations were observed for functional connectivity measures. Together, our results demonstrate that cortical-striatal-thalamic-cortical dysfunction across obsessive-compulsive disorder and gambling disorder may be better characterized by dimensional phenotypes than diagnostic comparisons, supporting investigation of quantitative liability phenotypes.

Description

Keywords

Compulsivity, DCM, Disinhibition, GD, Impulsivity, OCD, Adolescent, Adult, Brain, Brain Mapping, Female, Gambling, Humans, Image Interpretation, Computer-Assisted, Impulsive Behavior, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Obsessive-Compulsive Disorder, Phenotype, Young Adult

Journal Title

Neuroimage

Conference Name

Journal ISSN

1053-8119
1095-9572

Volume Title

202

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (110049/Z/15/Z)