{"doi":"10.1101/2024.09.02.24312960","title":"Distinct cognitive and functional connectivity features from healthy cohorts can identify clinical obsessive-compulsive disorder","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 clinical 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.","journal":"medRxiv","year":2024,"id":488927,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9413,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":30836,"name":"B.T. Thomas Yeo","orcid":"0000-0002-0119-3276","position":1,"is_corresponding":false},{"id":271041,"name":"Lachlan Webb","orcid":"0000-0002-5209-0314","position":2,"is_corresponding":false},{"id":34923,"name":"Andrew Zalesky","orcid":"0000-0003-2298-9908","position":3,"is_corresponding":false},{"id":230805,"name":"Paul B. Fitzgerald","orcid":"0000-0003-4217-8096","position":4,"is_corresponding":false},{"id":1333808,"name":"Oscar W. Murphy","orcid":"0000-0003-3184-9616","position":5,"is_corresponding":false},{"id":34919,"name":"Ye Ella Tian","orcid":"0000-0003-3107-5550","position":6,"is_corresponding":false},{"id":329513,"name":"Michael Breakspear","orcid":"0000-0003-4943-3969","position":7,"is_corresponding":false},{"id":877566,"name":"Caitlin V. Hall","orcid":"0000-0001-7013-6446","position":8,"is_corresponding":false},{"id":1027827,"name":"Sunah Choi","orcid":"0000-0001-5666-3485","position":9,"is_corresponding":false},{"id":630091,"name":"Minah Kim","orcid":"0000-0001-8668-0817","position":10,"is_corresponding":false},{"id":109318,"name":"Jun Soo Kwon","orcid":"0000-0002-1060-1462","position":11,"is_corresponding":false},{"id":552899,"name":"Luca Cocchi","orcid":"0000-0003-3651-2676","position":12,"is_corresponding":false},{"id":572495,"name":"Luke J. Hearne","orcid":"0000-0002-2014-1148","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T02:08:23.929823Z","pmid":"39281735","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}