The neural correlates and clinical characteristics of psychosis in the frontotemporal dementia continuum and the C9orf72 expansion

Emma M. Devenney*, Ramon Landin-Romero, Muireann Irish, Michael Hornberger, Eneida Mioshi, Glenda M. Halliday, Matthew C. Kiernan, John R. Hodges

*Corresponding author for this work

    Research output: Contribution to journalArticle

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    Abstract

    Objective

    This present study aims to address the gap in the literature regarding the severity and underlying neural correlates of psychotic symptoms in frontotemporal dementia with and without the C9orf72 gene expansion. 

    Methods

    Fifty-six patients with behavioural variant frontotemporal dementia (20 with concomitant amyotrophic lateral sclerosis) and 23 healthy controls underwent neuropsychological assessments, detailed clinical interview for assessment of psychosis symptoms, brain MRI and genetic testing. Carers underwent a clinical interview based upon the neuropsychiatric inventory. Patients were assessed at ForeFront, the Frontotemporal Dementia Research Group at Neuroscience Research Australia or at the Brain and Mind Centre, between January 2008 and December 2013. An index of psychosis was calculated, taking into account the degree and severity of psychosis in each case. Voxel-based morphometry analyses were used to explore relationships between the psychosis index and grey matter changes. 

    Results

    Thirty-four percent of frontotemporal dementia patients showed psychotic features. C9orf72 expansion cases were more likely to exhibit psychotic symptoms than non-carriers (64% vs. 26%; p=0.006), which were also more severe (psychotic index 23.1 vs. 8.1; p=0.002). Delusions comprised persecutory, somatic, jealous and grandiose types and were present in 57% of C9orf72 carriers and 19% of non-carriers (p=0.006). Auditory, visual or tactile hallucinations were present in 36% of C9orf72 carriers and 17% of non-carriers (p=0.13). Increased psychotic symptoms in C9orf72 expansion carriers correlated with atrophy in a distributed cortical and subcortical network that included discrete regions of the frontal, temporal and occipital cortices, as well as the thalamus, striatum and cerebellum.

    Conclusions 

    This study underlines the need to consider and assess for psychotic symptoms in the frontotemporal dementia-amyotrophic lateral sclerosis continuum particularly in those with C9orf72 gene expansions. The network of brain regions identified in this study is strikingly similar to that identified in other psychotic disorders such as schizophrenia, which suggests that treatment strategies in psychiatry may be beneficial for the management of psychotic symptoms in frontotemporal dementia.

    Original languageEnglish
    Pages (from-to)439-445
    Number of pages7
    JournalNeuroImage: Clinical
    Volume13
    DOIs
    Publication statusPublished - 2017

    Bibliographical note

    Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

    Keywords

    • frontotemporal dementia
    • amyotrophic lateral sclerosis
    • C9orf72 expansion
    • psychosis
    • schizophrenia
    • neuroimaging

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