Introduction Psychotic symptoms are now recognised to occur in patients with MND, often in association with FTD, and particularly in C9orf72 expansion carriers. As yet the impact of these symptoms on the clinical disease state is unknown and the relationship between severity and nature of these symptoms is not well understood. This study aimed to comprehensively explore the relationship between psychotic symptoms, clinical features, cognitive status and survival.

Methods In total 148 participants; MND (n=100) and MND-FTD (n=48), were enrolled in the study. A detailed clinical interview in addition to a neurological, neuropsychological and behavioural assessment, genetic testing and brain MRI was undertaken in each participant

Results Psychotic symptoms were present in 25% of the cohort. The majority of participants in the psychosis cohort were male (83%) and were negative for the C9orf72 expansion (70%). Psychotic symptoms in younger patients were more likely to be florid, require medication and delay diagnosis. Within the MND subgroup, patients with psychotic symptoms were more impaired in the cognitive subdomains of attention, memory and executive functioning and exhibited more disinhibition, apathy and stereotypy, than patients without psychotic symptoms (all p<0.01), but no differences were identified for the MND-FTD subgroup (all p>0.2). Symptoms of depression were more common in those without psychotic symptoms (p>0.1). Survival was prolonged for patients with psychotic symptoms (HR=4.7, 95% CI: 2.1–10, p<0.001)

Conclusion MND with psychosis represents a distinct clinical, cognitive and behavioural phenotype that has a positive impact on survival and may represent an overlap with psychiatric disorders.