title: Psychosis in Machado-Joseph Disease: Clinical Correlates, Pathophysiological Discussion, and Functional Brain Imaging. Expanding the Cerebellar Cognitive Affective Syndrome.
abstract: Machado-Joseph disease (MJD) is the most common spinocerebellar ataxia worldwide with a broad range of clinical manifestations, but psychotic symptoms were not previously characterized. We investigated the psychiatric manifestations of a large cohort of Brazilian patients with MJD in an attempt to characterize the presence of psychotic symptoms. We evaluated 112 patients with clinical and molecular diagnosis of MJD from February 2008 to November 2013. Patients with psychotic symptoms were referred to psychiatric evaluation and brain perfusion single-photon emission computed tomography (SPECT) analysis. A specific scale-Positive and Negative Syndrome Scale (PANSS)-was used to characterize psychotic symptoms in MJD patients. We also performed an autopsy from one of the patients with MJD and psychotic symptoms. Five patients presented psychotic symptoms. Patients with psychotic symptoms were older and had a late onset of the disease (p < 0.05). SPECT results showed that MJD patients had significant regional cerebral blood flow (rCBF) decrease in the cerebellum bilaterally and vermis compared with healthy subjects. No significant rCBF differences were found in patients without psychotic symptoms compared to patients with psychotic symptoms. The pathological description of a patient with MJD and psychotic symptoms revealed severe loss of neuron bodies in the dentate nucleus and substantia nigra. MJD patients with a late onset of the disease and older ones are at risk to develop psychotic symptoms during the disease progression. These clinical findings may be markers for an underlying cortical-cerebellar disconnection or degeneration of specific cortical and subcortical regions that may characterize the cerebellar cognitive affective syndrome.
authors: Division of General Neurology and Ataxia Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, 650 Pedro de Toledo St, Vila Clementino, São Paulo, 04039-002, São Paulo, Brazil. pbraganeto@gmail.com.|Center of Health Sciences, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil. pbraganeto@gmail.com.
authors: Pedro
authors: P
authors: Braga-Neto
authors: Division of General Neurology and Ataxia Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, 650 Pedro de Toledo St, Vila Clementino, São Paulo, 04039-002, São Paulo, Brazil.
authors: José Luiz
authors: JL
authors: Pedroso
authors: Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Ary
authors: A
authors: Gadelha
authors: Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Maura Regina
authors: MR
authors: Laureano
authors: Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Cristiano
authors: C
authors: de Souza Noto
authors: Western Australian Centre for Health & Ageing, Centre for Medical Research, University of Western Australia, Crawley, Australia.
authors: Griselda Jara
authors: GJ
authors: Garrido
authors: Division of General Neurology and Ataxia Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, 650 Pedro de Toledo St, Vila Clementino, São Paulo, 04039-002, São Paulo, Brazil.
authors: Orlando Graziani Povoas
authors: OG
authors: Barsottini
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001938:Brazil / Q000453:epidemiology; D002560:Cerebrovascular Circulation / Q000502:physiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D017827:Machado-Joseph Disease / Q000150:complications / Q000453:epidemiology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000150:complications / Q000453:epidemiology* / Q000378:metabolism* / Q000473:pathology; D015899:Tomography, Emission-Computed, Single-Photon
keywords: Cerebellar cognitive affective syndrome; Machado–Joseph disease; Psychosis; Spinocerebellar ataxia