Distinct cognitive and functional connectivity features from healthy cohorts can identify clinical obsessive-compulsive disorder

Mol Psychiatry. 2025 Dec 14. doi: 10.1038/s41380-025-03416-z. Online ahead of print.

ABSTRACT

Improving diagnostic accuracy of obsessive-compulsive disorder (OCD) using models of brain imaging data is a key goal of the field, but this objective is challenging due to the limited size and phenotypic depth of clinical datasets. Leveraging the phenotypic diversity in large non-clinical datasets such as the UK Biobank (UKBB), offers a potential solution to this problem. Nevertheless, it remains unclear whether classification models trained on non-clinical populations will generalise to individuals with clinical OCD. This question is also relevant for the conceptualisation of OCD; specifically, whether the symptomology of OCD exists on a continuum from normal to pathological. Here, we examined a recently published “meta-matching” model trained on functional connectivity data from five large normative datasets (N = 45,507) to predict cognitive, health and demographic variables. Specifically, we tested whether this model could classify OCD status in three independent datasets (N = 345). We found that the model could identify out-of-sample OCD individuals. Notably, the most predictive functional connectivity features mapped onto known cortico-striatal abnormalities in OCD and correlated with genetic brain expression maps previously implicated in the disorder. Further, the meta-matching model relied upon estimates of cognitive functions, such as cognitive flexibility and inhibition, to successfully predict OCD. These findings suggest that variability in non-clinical brain and behavioural features can discriminate clinical OCD status. These results support a dimensional and transdiagnostic conceptualisation of the brain and behavioural basis of OCD, with implications for research approaches and treatment targets.

PMID:41392094 | DOI:10.1038/s41380-025-03416-z