OPERA (Oxford Psychosis: Research & Application)

At OPERA, we study psychosis through a translational programme spanning neuroscience, experimental medicine, clinical trials, and clinical implementation. Our aim is to understand disease mechanisms and translate these insights into better treatments and improved care.

Our Research

Mechanisms of Psychosis

We investigate the neurobiological mechanisms that contribute to psychosis, with a particular focus on excitation–inhibition balance, dopaminergic function, and circuit-level dysfunction. Our work aims to connect molecular and cellular hypotheses to systems neuroscience and clinical symptoms, helping to explain how changes in brain function relate to hallucinations, delusions, cognitive difficulties, and broader functional impairment. This includes work using multimodal neuroimaging, computational modelling, and behavioural phenotyping. Current studies include:

• IN-PULSE – a study of hormonal influences on cognition and neurobiology in psychosis
• PEACE – an experimental medicine programme examining memantine and cognition

Mechanisms of Treatment

We undertake trials and experimental medicine studies to test whether treatments work, and also to understand how they work. These studies combine detailed cognitive and neurobiological phenotyping to determine how targeting specific mechanisms leads to improvements in symptoms. Current examples include:

• FOCUS – a trial examining the cognitive and mechanistic effects of xanomeline–trospium in early psychosis
• EXIBIT - a study designed to develop new ways of measuring excitatory and inhibitory activity in the living human brain

Understanding Data

We also develop computational and data-driven approaches to better understand heterogeneity in psychosis and predict treatment response. This includes machine learning models that integrate clinical, behavioural, cognitive, and neurobiological data, as well as cross-species approaches that aim to improve translation between preclinical and human research.
Our long-term goal is to support a more mechanistically informed approach to treatment development and clinical decision-making in psychosis.

CLINICAL INNOVATION

A major focus of OPERA is translating research findings into changes in clinical care. Through the INTEGRATE consortium, we develop international, evidence-based treatment guidelines and digital decision-support tools designed to make complex evidence more usable in real-world practice. In parallel, we work closely with Oxford Health NHS Foundation Trust to develop and evaluate improved models of care, including the TUNE-UP service for treatment-refractory psychosis. This work aims to ensure that advances in neuroscience and treatment research lead to tangible improvements in patient outcomes.