{"doi":"10.1101/2025.04.01.25325005","title":"Functional Coupling and Longitudinal Outcome Prediction in First-Episode Psychosis","abstract":"Background Clinical outcomes following a first episode of psychosis (FEP) are highly heterogeneous between patients. The identification of prognostic biomarkers would greatly facilitate personalized treatments. Psychosis patients often display brain-wide disruptions of inter-regional functional coupling (FC), with some being linked to symptom severity and remission. FC may thus hold prognostic potential for people experiencing psychosis. Methods Ninety antipsychotic-naive FEP patients (51% female, 15-25 years) were randomized to receive either antipsychotic or placebo tablets for 6 months alongside psychosocial interventions. A subset of these patients also completed functional magnetic resonance imaging (55 with usable data at baseline and 37 at 3 months), which was used to evaluate whether baseline FC, or 3-month change in FC, could predict 6- and 12-month changes in symptoms and functioning, quantified using the Brief Psychiatric Rating Scale and the Social and Occupational Functioning Assessment Scale, respectively. We considered three different cross-validated prediction algorithms: (i) connectome-based predictive modelling; (ii) kernel ridge regression; and (iii) multilayer meta-matching. Results All algorithms showed poor performance in predicting patients' 6- and 12-month changes in symptoms and functioning (all r mean < 0.3), and no model achieved significance via permutation testing (all p > 0.05). Conclusions Our findings suggest that brain-wide measures of FC may not be suitable for predicting extended clinical outcomes over a 6- to 12-month period in FEP patients.","journal":"medRxiv","year":2025,"id":563669,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":457021,"name":"Sidhant Chopra","orcid":"0000-0003-0866-3477","position":1,"is_corresponding":false},{"id":1276633,"name":"Alexander Holmes","orcid":"0009-0009-7012-6753","position":2,"is_corresponding":false},{"id":1276634,"name":"Shona M. Francey","orcid":"0000-0002-8305-8982","position":3,"is_corresponding":false},{"id":1276635,"name":"Brian O’Donoghue","orcid":"0000-0001-6240-6952","position":4,"is_corresponding":false},{"id":236923,"name":"Vanessa Cropley","orcid":"0000-0003-0029-1525","position":5,"is_corresponding":false},{"id":289181,"name":"Barnaby Nelson","orcid":"0000-0002-6263-2332","position":6,"is_corresponding":false},{"id":630209,"name":"Hok Pan Yuen","orcid":"0000-0002-1237-1322","position":7,"is_corresponding":false},{"id":771482,"name":"Kelly Allott","orcid":"0000-0002-0640-4634","position":8,"is_corresponding":false},{"id":869117,"name":"Mario Álvarez‐Jiménez","orcid":"0000-0002-3535-9086","position":9,"is_corresponding":false},{"id":1276637,"name":"Susy Harrigan","orcid":"0000-0002-1384-3969","position":10,"is_corresponding":false},{"id":62421,"name":"Christos Pantelis","orcid":"0000-0002-9565-0238","position":11,"is_corresponding":false},{"id":236745,"name":"Stephen J. Wood","orcid":"0000-0003-4186-5919","position":12,"is_corresponding":false},{"id":289189,"name":"Patrick D. McGorry","orcid":"0000-0002-3789-6168","position":13,"is_corresponding":false},{"id":478894,"name":"Alex Fornito","orcid":"0000-0001-9134-480X","position":14,"is_corresponding":false},{"id":1466917,"name":"Isaac Z Pope","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:56:17.117043Z","pmid":null,"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":[]}