Frequency and neural correlates related to psychosis in motor neurone disease

Psychosis is a challenging feature of the syndromes motor neurone disease (MND), frontotemporal dementia and their overlap. Clinically evident psychosis affects 5-10% of patients, and more in those with C9orf72 expansions. However, subthreshold psychosis features may be overlooked in the context of overriding concern for physical impairment. This prospective study aimed to establish the prevalence and severity of psychosis features in a population-representative sample of MND, and to identify the neural correlates of psychosis by structural magnetic resonance imaging. A three-tiered system was applied to recruit people with MND, with cognitive and psychosis screening (Tier 1: N=111 with the Edinburgh ALS Cognitive and Behavioural Screen), in-depth neuropsychiatric assessment (Tier 2: N-=60) and imaging (Tier 3: N=30). Age-, education- and sex-matched healthy controls were recruited to Tier 2 (N=30) and Tier 3 (N=20). Overt psychosis was identified in 10% of the Tier 1 cohort, whilst 46% showed milder and diverse neuropsychiatric change. Grey matter correlates of psychosis included atrophy of the cingulate cortex and the hippocampus. White matter correlates included compromised integrity along frontotemporal and temporal-parietal association pathways, especially those connecting the anterior temporal lobe. These grey and white matter changes in MND represent vulnerability to psychosis and are qualitatively similar to volumetric and white matter abnormalities observed in other primary psychotic disorders. Neuropsychiatric features are common, even though overt psychosis is identified in a minority of people with motor neurone disease.