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Cross-Sectional Study on Prevalences of Psychiatric Disorders in Mutation Carriers of Huntington's Disease Compared With Mutation-Negative First-Degree Relatives

Erik van Duijn, M.D.; Elisabeth M. Kingma, M.Sc., M.Phil.; Reinier Timman, Ph.D.; Frans G. Zitman, Ph.D.; Aad Tibben, Ph.D.; Raymund A. C. Roos, Ph.D.; and Rose C. van der Mast, Ph.D.

Objective: To investigate the prevalences of formal DSM-IV diagnoses in pre-motor-symptomatic and motor-symptomatic mutation carriers at different stages of Huntington's disease compared to a control group of first-degree noncarrier relatives and the general population.

Method: Between May 2004 and August 2006, 154 verified mutation carriers and 56 verified noncarriers were recruited from the outpatient clinics of the Neurology and Clinical Genetics departments of Leiden University Medical Center and from a regional nursing home. To assess the 12-month prevalences of DSM-IV diagnoses, the sections for depression, mania, anxiety, obsessive-compulsive disorder, and psychosis/schizophrenia of the Composite International Diagnostic Interview were used. Prevalences in the Dutch general population were extracted from the Netherlands Mental Health Survey and Incidence Study (NEMESIS).

Results: Both presymptomatic and symptomatic mutation carriers portrayed significantly more major depressive disorder (p = .001 and p < .001, respectively) and obsessive-compulsive disorder (p = .003 and p = .01, respectively) than the general population. Symptomatic mutation carriers also showed an increased prevalence (p = .01) of nonaffective psychosis. Psychiatric disorders were more prevalent, although not significantly (p = .06), in mutation carriers compared to first-degree relatives who were noncarriers. Noncarriers did not differ from the general population.

Conclusion: Psychiatric disorders occur frequently in Huntington's disease, often before motor symptoms appear. In addition, first-degree noncarrier relatives do not show more psychiatric disorders compared to the general population, although they grew up in comparable, potentially stressful circumstances. Taking these findings together, psychopathology in Huntington's disease seems predominantly due to cerebral degeneration rather than to shared environmental risk factors.


(J Clin Psychiatry 2008;69:1804-1810. Online Ahead of Print November 4, 2008.)

Received Feb. 24, 2008; accepted June 16, 2008. From the Department of Psychiatry (Drs. van Duijn, Timman, Zitman, and van der Mast and Ms. Kingma), the Department of Clinical Genetics (Drs. Timman and Tibben), and the Department of Neurology (Drs. Timman, Tibben, and Roos), Leiden University Medical Center; and the Center for Mental Health Care, Duin- en Bollenstreek, Rivierduinen, Voorhout (Dr. van Duijn), The Netherlands.

Preliminary results of this study were presented at the national meeting of the Dutch Psychiatric Association, May 2007, Groningen, The Netherlands, and at the 3rd World Congress on Huntington's Disease, September 8-11, 2007, Dresden, Germany.

The authors acknowledge Yvette A. M. Grimbergen, M.D., neurologist; Lucienne B. van der Meer, M.Sc., psychologist; Hans Claus, M.Sc., psychologist; and Lani Liem, M.D., nursing home physician. These individuals report no financial conflicts of interest.

The authors report no financial affiliations or other relationships relevant to the subject of this article.

Corresponding author and reprints: Erik van Duijn, M.D., Leiden University Medical Center, Department of Psychiatry, B1-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands (e-mail: