title: The neural correlates and clinical characteristics of psychosis in the frontotemporal dementia continuum and theC9orf72expansion.
abstract: 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 theC9orf72gene expansion.
  
  
  
  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.
  
  
  
  Thirty-four percent of frontotemporal dementia patients showed psychotic features.C9orf72expansion 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% ofC9orf72carriers and 19% of non-carriers (p= 0.006). Auditory, visual or tactile hallucinations were present in 36% ofC9orf72carriers and 17% of non-carriers (p= 0.13). Increased psychotic symptoms inC9orf72expansion 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.
  
  
  
  This study underlines the need to consider and assess for psychotic symptoms in the frontotemporal dementia-amyotrophic lateral sclerosis continuum particularly in those withC9orf72gene 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.
authors.affiliation: Neuroscience Research Australia, Barker Street, Sydney, NSW 2031, Australia; University of New South Wales, Sydney, NSW 2031, Australia; Brain and Mind Research Institute, Camperdown, Sydney, NSW 2050, Australia; ARC Centre of Excellence in Cognition and its Disorders, Macquarie University, Sydney, NSW 2109, Australia.
authors.forename: Emma M
authors.initials: EM
authors.lastname: Devenney
authors.affiliation: Neuroscience Research Australia, Barker Street, Sydney, NSW 2031, Australia; University of New South Wales, Sydney, NSW 2031, Australia; ARC Centre of Excellence in Cognition and its Disorders, Macquarie University, Sydney, NSW 2109, Australia.
authors.forename: Ramon
authors.initials: R
authors.lastname: Landin-Romero
authors.affiliation: Neuroscience Research Australia, Barker Street, Sydney, NSW 2031, Australia; University of New South Wales, Sydney, NSW 2031, Australia; ARC Centre of Excellence in Cognition and its Disorders, Macquarie University, Sydney, NSW 2109, Australia.
authors.forename: Muireann
authors.initials: M
authors.lastname: Irish
authors.affiliation: University of East Anglia, Norwich NR4 7TJ, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Hornberger
authors.affiliation: University of East Anglia, Norwich NR4 7TJ, United Kingdom.
authors.forename: Eneida
authors.initials: E
authors.lastname: Mioshi
authors.affiliation: Neuroscience Research Australia, Barker Street, Sydney, NSW 2031, Australia; University of New South Wales, Sydney, NSW 2031, Australia.
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.affiliation: Neuroscience Research Australia, Barker Street, Sydney, NSW 2031, Australia; University of New South Wales, Sydney, NSW 2031, Australia; Brain and Mind Research Institute, Camperdown, Sydney, NSW 2050, Australia.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
authors.affiliation: Neuroscience Research Australia, Barker Street, Sydney, NSW 2031, Australia; University of New South Wales, Sydney, NSW 2031, Australia; ARC Centre of Excellence in Cognition and its Disorders, Macquarie University, Sydney, NSW 2109, Australia.
authors.forename: John R
authors.initials: JR
authors.lastname: Hodges
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics; D000073885:C9orf72 Protein / Q000235:genetics*; D015897:Comorbidity; D005260:Female; D057180:Frontotemporal Dementia / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human
keywords: Amyotrophic lateral sclerosis; C9orf72 expansion; Frontotemporal dementia; Neuroimaging; Psychosis; Schizophrenia