title: Neuropsychiatric symptoms are very common in premanifest and early stage Huntington's Disease.
abstract: BACKGROUND
  Neuropsychiatric symptoms are common features of Huntington's disease (HD). Whereas most studies have focused on cognitive and neuroimaging markers of disease progression, little is known about the prevalence of neuropsychiatric symptoms in premanifest mutation carriers far-from and close-to disease onset.
  
  
  METHODS
  We obtained neurological, cognitive and behavioral data from 230 participants classified as premanifest far-from (preHD-A) and close-to (preHD-B) motor-based disease onset, early-symptomatic (early-HD), and healthy controls. Frequency and severity of neuropsychiatric symptoms were assessed with the short Problem Behaviors Assessment for HD (PBA-s). The odds-ratio (OR) to present symptoms in the clinical range was calculated using the control group as reference. Logistic regression analysis was used to explore relationships between neuropsychiatric symptoms and medication use.
  
  
  RESULTS
  Prevalence of depression was similar in all groups. Apathy was already present in 32% of preHD-A increasing to 62% of early-HD patients. The probability of presenting apathetic symptoms was 15-88 times higher in preHD-A and preHD-B respectively than in healthy controls. Irritability and executive dysfunction were present in both preHD-B and early-HD.
  
  
  CONCLUSIONS
  Neuropsychiatric symptoms are highly prevalent in HD, already in the premanifest stage, with increasing prevalence of irritability, apathy and executive dysfunction closer to onset. Compared to controls, HD mutation carriers have the highest probability to develop apathy, with an increasing prevalence along disease stages. Our findings confirm the high prevalence of neuropsychiatric symptoms in HD, already many years before the onset of motor symptoms, with apathy as an early manifestation and core neuropsychiatric feature of the disease.
authors.affiliation: Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Spain; Universitat Oberta de Catalunya (UOC), Barcelona, Spain.
authors.forename: Saul
authors.initials: S
authors.lastname: Martinez-Horta
authors.affiliation: Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Perez-Perez
authors.affiliation: Department of Psychiatry, Leiden University Medical Centre, Leiden, and Centre for Mental Health Care Delfland, Delft, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: van Duijn
authors.affiliation: Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Spain; Universitat Oberta de Catalunya (UOC), Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Fernandez-Bobadilla
authors.affiliation: Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Carceller
authors.affiliation: Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Pagonabarraga
authors.affiliation: Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Pascual-Sedano
authors.affiliation: Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Campolongo
authors.affiliation: Hospital Mare de Déu de la Mercé, Barcelona, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Ruiz-Idiago
authors.affiliation: Faculty of Medicine, Autonomous University of Barcelona, Spain.
authors.forename: Frederic
authors.initials: F
authors.lastname: Sampedro
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: G Bernhard
authors.initials: GB
authors.lastname: Landwehrmeyer
authors.affiliation: Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Spain; Universitat Oberta de Catalunya (UOC), Barcelona, Spain. Electronic address: jkulisevsky@santpau.cat.
authors.forename: Jaime
authors.initials: J
authors.lastname: Kulisevsky
mesh_terms: D000328:Adult; D057565:Apathy; D003072:Cognition Disorders / Q000453:epidemiology / Q000209:etiology; D003430:Cross-Sectional Studies; D003863:Depression / Q000453:epidemiology; D056344:Executive Function; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications* / Q000523:psychology*; D007508:Irritable Mood; D008297:Male; D015995:Prevalence; D011446:Prospective Studies
keywords: Apathy; Behavior; Biomarker; Huntington's disease; Neuropsychiatry