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

Background 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 (CSTC) function. However, whether impulsivity and compulsivity in clinical disorders is continuous with the healthy population and explains CSTC dysfunction across different disorders remains unclear. Methods We characterized the relationship between CSTC effective connectivity, estimated using dynamic causal modelling of functional magnetic resonance imaging data, and dimensional phenotypes of impulsivity and compulsivity in two symptomatically distinct but phenotypically related disorders, obsessive-compulsive disorder (OCD) and gambling disorder (GD). 487 online participants provided data for modelling of dimensional phenotypes. These data were combined with 34 OCD patients, 22 GD patients, and 39 healthy controls, who underwent functional magnetic resonance imaging. Results 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 increased bottom-up connectivity in the ventral circuit, and higher compulsivity correlated with reduced bottom-up connectivity in the dorsal circuit. Similar changes in effective connectivity were observed with increasing clinical severity that were not accounted for by 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. Conclusions CSTC dysfunction across OCD and GD is better characterized by dimensional phenotypes than diagnostic comparisons, supporting investigation of quantitative liability phenotypes. L.P. was supported by an Australian Postgraduate Award. J.T. was supported by National Health and Medical Research Council (ID:1002458, 1046054). A.F. was supported by the Charles and Sylvia Viertel Foundation, the Australian Research Council (ID: FT130100589) and the National Health and Medical Research Council (ID: 3251213, 3251250, 3251392). M.Y. was supported by a National Health and Medical Research Council Fellowship (ID: 1117188), Monash University and the David Winston Turner Endowment Fund.