Characterising Negative Symptoms in Schizophrenia: CHANSS study protocol

Negative symptoms in schizophrenia, particularly motivational deficits, pose significant challenges to treatment and recovery. Despite their profound impact on functional outcomes, these symptoms remain poorly understood and inadequately addressed by current interventions. The CHANSS (Characterising Negative Symptoms in Schizophrenia) study aims to dissect the cognitive mechanisms underlying motivational impairments by focusing on three interconnected domains: executive cognition, motivational cognition, and meta-cognition. This large, international, cross-sectional study recruits a heterogeneous sample of patients across illness stages (from first-episode psychosis to treatment-resistant schizophrenia) and uses a comprehensive cognitive battery, clinical scales, self-report measures, and computerised cognitive tasks. Four novel tasks assess key processes in motivated behaviour: option generation, reward-based decision-making, risk sensitivity, and performance self-evaluation. By incorporating control for secondary influences like depression, psychosis, sedation, and illness chronicity, the study seeks to identify distinct cognitive and behavioural subtypes within motivational dysfunction. CHANSS tests the hypothesis that specific patient profiles exhibit predominant impairments in one or more cognitive domains, which may differentially affect goal-directed behaviour. The study design allows exploration of hierarchical relationships between cognitive processes, such as how executive deficits may cascade to impair motivation and self-evaluation. Ultimately, CHANSS aims to advance mechanistic understanding of motivational deficits in schizophrenia and pave the way for personalised, targeted interventions. Its findings may inform future clinical trials and contribute to a shift away from one-size-fits-all approaches toward more effective, stratified treatment strategies in schizophrenia.