The analysis of schizophrenia-like psychosis in dentatorubral-pallidoluysian atrophy

BackgroundDentatorubral-pallidoluysian atrophy (DRPLA) is a progressive neurodegenerative disorder caused by expanded CAG repeats in the ATN1 gene, characterized by cerebellar ataxia, seizures, tremors, and myoclonus. Although approximately 10% of patients with DRPLA reportedly develop schizophrenia...

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Main Authors: Ichiko Ikegami, Yuka Mitsuhashi Koike, Hideki Hayashi, Sachiko Hirokawa, Shoichiro Ando, Tomohiko Ishihara, Osamu Onodera
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Neurology
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Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2025.1564856/full
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author Ichiko Ikegami
Yuka Mitsuhashi Koike
Hideki Hayashi
Sachiko Hirokawa
Shoichiro Ando
Tomohiko Ishihara
Osamu Onodera
author_facet Ichiko Ikegami
Yuka Mitsuhashi Koike
Hideki Hayashi
Sachiko Hirokawa
Shoichiro Ando
Tomohiko Ishihara
Osamu Onodera
author_sort Ichiko Ikegami
collection DOAJ
description BackgroundDentatorubral-pallidoluysian atrophy (DRPLA) is a progressive neurodegenerative disorder caused by expanded CAG repeats in the ATN1 gene, characterized by cerebellar ataxia, seizures, tremors, and myoclonus. Although approximately 10% of patients with DRPLA reportedly develop schizophrenia-like psychosis (SLP), the distinct association between the clinical course of DRPLA and SLP remains unclear. This study aimed to elucidate the clinical features of SLP in patients with DRPLA.MethodsWe reviewed 22 cases of pathologically or genetically confirmed DRPLA with SLP, including 21 from the literature and one from our institution. Patient data, including clinical features, treatment information, and disease course, were extracted and analyzed.ResultsThe age of onset was categorized as juvenile (n = 6), early adult (n = 8), and late adult (n = 8). Initially, 10 patients presented with motor symptoms, with six exhibiting psychiatric symptoms and six with both motor and psychiatric symptoms simultaneously. Furthermore, three patients were initially diagnosed with schizophrenia, while four experienced progressive worsening of psychiatric symptoms. The number of CAG repeats ranged from 57 to 76 (mean, 66.0) in the 10 patients with a genetic diagnosis. Summarily, 12 patients received psychotropic medications, with nine showing improvement in delusions and hallucinations.ConclusionSLP can manifest across all DRPLA forms (juvenile-, early adult-, and late adult-onset) and may precede or follow motor symptoms. The clinical course and efficacy of psychotropic medications in patients with DRPLA and SLP suggest a shared pathogenesis between DRPLA and schizophrenia.
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spelling doaj-art-2b7776b399f64aba92513fe45c40625b2025-08-20T02:16:44ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-04-011610.3389/fneur.2025.15648561564856The analysis of schizophrenia-like psychosis in dentatorubral-pallidoluysian atrophyIchiko Ikegami0Yuka Mitsuhashi Koike1Hideki Hayashi2Sachiko Hirokawa3Shoichiro Ando4Tomohiko Ishihara5Osamu Onodera6Department of Neurology, Brain Research Institute, Niigata University, Niigata, JapanDepartment of Molecular Neuroscience, Brain Research Institute, Niigata University, Niigata, JapanDepartment of Neurology, Brain Research Institute, Niigata University, Niigata, JapanDepartment of Molecular Neuroscience, Brain Research Institute, Niigata University, Niigata, JapanDepartment of Neurology, Brain Research Institute, Niigata University, Niigata, JapanAdvanced Treatment of Neurological Diseases Branch, Brain Research Institute, Niigata University, Niigata, JapanDepartment of Neurology, Brain Research Institute, Niigata University, Niigata, JapanBackgroundDentatorubral-pallidoluysian atrophy (DRPLA) is a progressive neurodegenerative disorder caused by expanded CAG repeats in the ATN1 gene, characterized by cerebellar ataxia, seizures, tremors, and myoclonus. Although approximately 10% of patients with DRPLA reportedly develop schizophrenia-like psychosis (SLP), the distinct association between the clinical course of DRPLA and SLP remains unclear. This study aimed to elucidate the clinical features of SLP in patients with DRPLA.MethodsWe reviewed 22 cases of pathologically or genetically confirmed DRPLA with SLP, including 21 from the literature and one from our institution. Patient data, including clinical features, treatment information, and disease course, were extracted and analyzed.ResultsThe age of onset was categorized as juvenile (n = 6), early adult (n = 8), and late adult (n = 8). Initially, 10 patients presented with motor symptoms, with six exhibiting psychiatric symptoms and six with both motor and psychiatric symptoms simultaneously. Furthermore, three patients were initially diagnosed with schizophrenia, while four experienced progressive worsening of psychiatric symptoms. The number of CAG repeats ranged from 57 to 76 (mean, 66.0) in the 10 patients with a genetic diagnosis. Summarily, 12 patients received psychotropic medications, with nine showing improvement in delusions and hallucinations.ConclusionSLP can manifest across all DRPLA forms (juvenile-, early adult-, and late adult-onset) and may precede or follow motor symptoms. The clinical course and efficacy of psychotropic medications in patients with DRPLA and SLP suggest a shared pathogenesis between DRPLA and schizophrenia.https://www.frontiersin.org/articles/10.3389/fneur.2025.1564856/fulldentatorubral-pallidoluysian atrophypolyglutamine diseasepsychosisschizophreniapsychotropic medications
spellingShingle Ichiko Ikegami
Yuka Mitsuhashi Koike
Hideki Hayashi
Sachiko Hirokawa
Shoichiro Ando
Tomohiko Ishihara
Osamu Onodera
The analysis of schizophrenia-like psychosis in dentatorubral-pallidoluysian atrophy
Frontiers in Neurology
dentatorubral-pallidoluysian atrophy
polyglutamine disease
psychosis
schizophrenia
psychotropic medications
title The analysis of schizophrenia-like psychosis in dentatorubral-pallidoluysian atrophy
title_full The analysis of schizophrenia-like psychosis in dentatorubral-pallidoluysian atrophy
title_fullStr The analysis of schizophrenia-like psychosis in dentatorubral-pallidoluysian atrophy
title_full_unstemmed The analysis of schizophrenia-like psychosis in dentatorubral-pallidoluysian atrophy
title_short The analysis of schizophrenia-like psychosis in dentatorubral-pallidoluysian atrophy
title_sort analysis of schizophrenia like psychosis in dentatorubral pallidoluysian atrophy
topic dentatorubral-pallidoluysian atrophy
polyglutamine disease
psychosis
schizophrenia
psychotropic medications
url https://www.frontiersin.org/articles/10.3389/fneur.2025.1564856/full
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