DIALOG: Understanding Disorganisation: A Language-focused Global Initiative in Psychosis

Social connectedness is critical to recovery from psychosis in mental disorders and underpins vocational success. Persistent disorganisation of speech and language powerfully disrupts social interaction and perpetuates stigma, yet we know little about its causes. DIALOG, an international interdisciplinary initiative co-conceived with lived-experience experts, aims to address this and provide clarity on the neurobiological underpinnings of disorganisation. By focusing on patients’ everyday language use, rather than traditional clinical ratings, DIALOG seeks to identify the predictive computations implemented ‘on-the-fly’ by our brain when we interact with others, and how they break down to cause disorganisation. We leverage state-of-the-art Large Language Models (LLM) to extract objective markers of disorganisation from naturalistic speech, sampled longitudinally from patients with severe mental disorders. Combining LLM with large-scale new and legacy data from neuroimaging tools (MRI/PET/MEG; >3,000 patients) for the first time, we will identify the cardinal neurophysiological processes (synaptic density, neuronal connectivity and oscillatory dynamics) that underlie the computational failures behind disorganisation. In parallel, we will catalogue potential treatments and build the capacity for their multi-site evaluations, facilitating future trials and accelerating clinical translation. DIALOG will pioneer a computationally informed, molecular-to-systems-level account of disorganisation, identifying the precise mechanisms that can be targeted with novel treatments.