Background: Irritability, depression and apathy are frequently reported neuropsychiatric symptoms of Huntington's disease (HD). Objective: This study investigated the course of irritability, depression and apathy in HD during a 2-year follow-up period. Methods: In 121 HD mutation carriers the presence of irritability, depression and apathy was measured with the Problem Behaviours Assessment (PBA). Multivariate linear regression analysis was performed to assess their relationships with the change of the motor score of the Unified Huntington's Disease Rating Scale (UHDRS-m) in premotor symptomatic (n = 46) and motor symptomatic mutation carriers (n = 75). Results: The median depression score of all participants decreased (p = 0.002), whereas irritability and apathy scores did not change significantly. In the total group of mutation carriers, a borderline significant association was found between an increase in motor symptoms and an increase in irritability (p = 0.05), and a trend was found for the association between an increase in motor symptoms and a decrease in depression (p = 0.06). Only in the at baseline premotor symptomatic mutation carriers was an increase in motor symptoms significantly related to an increase in irritability (p = 0.02). Conclusion: An increase in motor symptoms in the at baseline premotor symptomatic mutation carriers is related to an increase in irritability, which may be an early and sensitive marker for disease progression.

Keywords:
Huntington’s disease, Irritability, Depression, Apathy, Movement disorders, Neuropsychiatry
1.
Walker FO: Huntington's disease. Lancet 2007;369:218-228.
2.
Huntington's Disease Collaborative Research Group: A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993;72:971-983.
3.
Phillips W, Shannon KM, Barker RA: The current clinical management of Huntington's disease. Mov Disord 2008;23:1491-1504.
4.
van Duijn E, Kingma EM, van der Mast RC: Psychopathology in verified Huntington's disease gene carriers. J Neuropsychiatry Clin Neurosci 2007;19:441-448.
5.
Duff K, Paulsen JS, Beglinger LJ, Langbehn DR, Stout JC, Predict-HD Investigators of the Huntington Study Group: Psychiatric symptoms in Huntington's disease before diagnosis: the Predict-HD study. Biol Psychiatry 2007;62:1341-1346.
6.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. Washington, American Psychiatric Association, 2000.
7.
Huntington Study Group: Unified Huntington's Disease Rating Scale: reliability and consistency. Mov Disord 1996;11:136-142.
8.
Craufurd D, Thompson JC, Snowden JS: Behavioural changes in Huntington Disease. Neuropsychiatry Neuropsychol Behav Neurol 2001;14:219-226.
9.
Paulsen JS, Nehl C, Hoth KF, Kanz JE, Benjamin M, Conybeare R, McDowell B, Turner B, Huntington Study Group: Depression and stages of Huntington's disease. J Neuropsychiatry Clin Neurosci 2005;17:496-502.
10.
Kingma EM, van Duijn E, Timman R, van der Mast RC, Roos RAC: Behavioural problems in Huntington's disease using the Problem Behaviours Assessment. Gen Hosp Psychiatry 2008;30:155-161.
11.
Tabrizi SJ, Langbehn DR, Leavitt BR, Roos RAC, Durr A, Craufurd D, Kennard C, Hicks SL, Fox NC, Scahill RI, Borowsky B, Tobin AJ, Rosas HD, Johnson H, Reilmann R, Landwehrmeyer B, Stout JC, TRACK-HD investigators: Biological and clinical manifestations of Huntington's disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data. Lancet Neurol 2009;8:791-801.
12.
Burns A, Folstein S, Brandt J, Folstein M: Clinical assessment of irritability, aggression, and apathy in Huntington and Alzheimer disease. J Nerv Ment Dis 1990;178:20-26.
13.
van Duijn E, Giltay EJ, Zitman FG, Roos RAC, van der Mast RC: Measurement of psychopathology in Huntington's disease: the critical role of caregivers. J Nerv Ment Dis 2010;198:329-333.
14.
Reedeker W, Bouwens JA, van Duijn E, Giltay EJ, Roos RAC, van der Mast RC: Incidence, course and predictors of apathy in Huntington's disease: a two-year prospective study. J Neuropsychiatry Clin Neurosci 2011;23:434-441.
15.
Paulsen JS, Ready RE, Hamilton JM, Mega MS, Cummings JL: Neuropsychiatric aspects of Huntington's disease. J Neurol Neurosurg Psychiatry 2001;71:310-314.
16.
van Duijn E, Kingma EM, Timman R, Zitman FG, Tibben A, Roos RAC, van der Mast RC: Cross-sectional study on prevalences of psychiatric disorders in mutation carriers of Huntington's disease compared with mutation-negative first-degree relatives. J Clin Psychiatry 2008;69:1804-1810.
17.
Vassos E, Panas M, Kladi A, Vassilopoulos D: Effect of CAG repeat length on psychiatric disorders in Huntington's disease. J Psychiatr Res 2008;42:544-549.
18.
Shoulson I, Fahn S: Huntington disease: clinical care and evaluation. Neurology 1979;29:1-3.
19.
Folstein MF, Folstein SE, McHugh PR: Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198.
20.
Marder K, Zhao H, Myers RH, Cudkowicz M, Kayson E, Kieburtz K, Orme C, Paulsen J, Penney JB Jr, Siemers E, Shoulson I: Rate of functional decline in Huntington's disease. Huntington Study Group. Neurology 2000;54:452-458.
21.
Rickards H, De Souza J, van Walsem M, van Duijn E, Simpson SA, Squitieri F, Landwehrmeyer B, European Huntington's Disease Network: Factor analysis of behavioural symptoms in Huntington's disease. J Neurol Neurosurg Psychiatry 2011;82:411-412.
22.
Berrios GE, Wagle AC, Marková IS, Wagle SA, Rosser A, Hodges JR: Psychiatric symptoms in neurologically asymptomatic Huntington's disease gene carriers: a comparison with gene negative at risk subjects. Acta Psychiatr Scand 2002;105:224-230.
23.
Kirkwood SC, Siemers E, Viken R, Hodes ME, Conneally PM, Christian JC, Foroud T: Longitudinal personality changes among presymptomatic Huntington disease gene carriers. Neuropsychiatry Neuropsychol Behav Neurol 2002;15:192-197.
24.
Julien CL, Thompson JC, Wild S, Yardumian P, Snowden JS, Turner G, Craufurd D: Psychiatric disorders in pre-clinical Huntington's disease. J Neurol Neurosurg Psychiatry 2007;78:939-943.
25.
Orth M, European Huntington's Disease Network: Observing Huntington's disease: the European Huntington's Disease Network's REGISTRY. PLoS Curr 2010, DOI: 10.1371/currents.RRN1184.
26.
Vassos E, Panas M, Kladi A, Vassilopoulos D: Higher levels of extroverted hostility detected in gene carriers at risk for Huntington's disease. Biol Psychiatry 2007;62:1347-1352.
27.
Tabrizi SJ, Scahili RI, Durr A, Roos RAC, Leavitt BR, Jones R, Landwehrmeyer B, et al, TRACK-HD Investigators: Biological and clinical changes in premanifest and early stage Huntington's disease in the TRACK-HD study: the 12-month longitudinal analysis. Lancet Neurol 2011;10:31-42.
28.
Gargiulo M, Lejeune S, Tanguy ML, Lahlou-Laforêt K, Faudet A, Cohen D, Feingold J, Durr A: Long-term outcome of presymptomatic testing in Huntington disease. Eur J Hum Genet 2009;17:165-171.
29.
Kirkwood SC, Su JL, Conneally PM, Foroud T: Progression of symptoms in the early and middle stages of Huntington's disease. Arch Neurol 2001;58:273-278.
30.
Paulsen JS, Wang CH, Duff K, Barker R, Nance M, Beglinger L, Moser D, Williams JK, Simpson S, Langbehn D, van Kammen DP, PREDICT-HD Investigators of the Huntington Study Group: Challenges assessing clinical endpoints in early Huntington disease. Mov Disord 2010;25:2595-2603.
© 2013 S. Karger AG, Basel
2013
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.