A major international study, co-led by the University of Oxford’s Department of Psychiatry and Oxford Health NHS Foundation Trust (OHFT), has uncovered vital insights into the brain changes linked to treatment-resistant psychosis, offering fresh hope for earlier diagnosis and more targeted care.

Published in the journal Schizophrenia, the research tracked 87 individuals experiencing a first episode of non-affective psychosis, alongside 118 healthy controls, using resting-state functional MRI over a six-year period. Crucially, 30 participants went on to develop treatment-resistant psychosis, a condition affecting around one in four people with psychosis and often recognised only after years of unsuccessful medication trials.

Clinical data was collected through the Early Intervention Service at the Instituto Psiquiátrico José Horwitz Barak in Santiago, Chile. Chilean researchers were central to the project, contributing to both data collection and analysis. This builds on Chile’s leadership in early psychosis care in Latin America, including the OnTrack Chile programme, which adapts global best practice to local needs.

The Oxford team, including researchers from OHFT, studied brain circuits that help control emotions, thinking and movement. They found that people who responded well to treatment had stable brain patterns, while those with treatment-resistant psychosis showed clear and changing differences in a key brain area called the ventral striatum. These changes were especially noticeable in how this area connected with parts of the brain linked to symptom improvement.

This is the first longitudinal study of its kind to identify early neural markers that could help predict treatment resistance. It builds on Oxford’s growing portfolio of precision psychiatry research, supported by the NIHR Oxford Health Biomedical Research Centre, which aims to personalise mental health care through cutting-edge science.

Rob McCutcheon

Co-author of the paper, Associate Professor Robert McCutcheon, member of the University of Oxford’s Department of Psychiatry and OHFT consultant psychiatrist, said: “These findings bring us closer to identifying who may not respond to standard treatments early on, allowing us to intervene more effectively and reduce the long delays that many patients currently face.”

As the field moves towards biomarker-driven psychiatry, Oxford’s leadership in early psychosis research continues to shape the future of mental health care

Senior author Nicolas Crossley, Visiting Professor at the Department of Psychiatry at Oxford and Assistant Professor at Pontificia Universidad Católica in Chile, said: “This research is a good example of how clinical teams and scientists in different countries can work together to improve the lives of people with psychosis around the world.”