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

Department of Psychiatry, Leiden University Medical Center, B1-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 12/2008; 69(11):1804-10. DOI: 10.4088/JCP.v69n1116
Source: PubMed


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.
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).
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.
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.

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    • "Major depression is the most common symptom among pre-symptomatic HD carriers, although some patients will have only part of the symptoms of the major depression, or limited in intensity or time (Epping and Paulsen, 2011; Reedeker et al., 2012). Maniac depressive disorder is not particularly prevalent in HD (Van Duijn et al., 2008; Epping and Paulsen, 2011). Mood disturbances may precede the onset of the motor phenotype by 4–10 years, making them one of the earliest symptoms of HD. "
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    ABSTRACT: Huntington's disease (HD) is a neurodegenerative disorder that is best known for its effect on motor control. Mood disturbances such as depression, anxiety, and irritability also have a high prevalence in patients with HD, and often start before the onset of motor symptoms. Various rodent models of HD recapitulate the anxiety/depressive behavior seen in patients. HD is caused by an expanded polyglutamine stretch in the N-terminal part of a 350 kDa protein called huntingtin (HTT). HTT is ubiquitously expressed and is implicated in several cellular functions including control of transcription, vesicular trafficking, ciliogenesis, and mitosis. This review summarizes progress in efforts to understand the cellular and molecular mechanisms underlying behavioral disorders in patients with HD. Dysfunctional HTT affects cellular pathways that are involved in mood disorders or in the response to antidepressants, including BDNF/TrkB and serotonergic signaling. Moreover, HTT affects adult hippocampal neurogenesis, a physiological phenomenon that is implicated in some of the behavioral effects of antidepressants and is linked to the control of anxiety. These findings are consistent with the emerging role of wild-type HTT as a crucial component of neuronal development and physiology. Thus, the pathogenic polyQ expansion in HTT could lead to mood disorders not only by the gain of a new toxic function but also by the perturbation of its normal function.
    Frontiers in Behavioral Neuroscience 04/2014; 8:135. DOI:10.3389/fnbeh.2014.00135 · 3.27 Impact Factor
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    • "Psychiatric symptoms abound in HD (Leroi et al., 2002), including psychosis (Lovestone et al., 1996), irritability, anxiety, apathy (van Duijn et al., 2007), and obsessive and compulsive symptoms (Beglinger et al., 2008; van Duijn et al., 2008). However, depression is among the most prevalent of psychiatric symptoms, with a lifetime prevalence of major depression reported to be up to and over 50% in patients; moreover, depression is often diagnosed years if not decades prior motor symptom onset (Shiwach, 1994; Naarding et al., 2001; Paulsen et al., 2001, 2005; Duff et al., 2007; van Duijn et al., 2008; Gargiulo et al., 2009). "
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    ABSTRACT: Huntington's disease (HD) is an autosomal dominant disorder caused by a tandem repeat expansion encoding an expanded tract of glutamines in the huntingtin protein. HD is progressive and manifests as psychiatric symptoms (including depression), cognitive deficits (culminating in dementia), and motor abnormalities (including chorea). Having reached the twentieth anniversary of the discovery of the "genetic stutter" which causes HD, we still lack sophisticated insight into why so many HD patients exhibit affective disorders such as depression at very early stages, prior to overt appearance of motor deficits. In this review, we will focus on depression as the major psychiatric manifestation of HD, discuss potential mechanisms of pathogenesis identified from animal models, and compare depression in HD patients with that of the wider gene-negative population. The discovery of depressive-like behaviors as well as cellular and molecular correlates of depression in transgenic HD mice has added strong support to the hypothesis that the HD mutation adds significantly to the genetic load for depression. A key question is whether HD-associated depression differs from that in the general population. Whilst preclinical studies, clinical data, and treatment responses suggest striking similarities, there are also some apparent differences. We discuss various molecular and cellular mechanisms which may contribute to depression in HD, and whether they may generalize to other depressive disorders. The autosomal dominant nature of HD and the existence of models with excellent construct validity provide a unique opportunity to understand the pathogenesis of depression and associated gene-environment interactions. Thus, understanding the pathogenesis of depression in HD may not only facilitate tailored therapeutic approaches for HD sufferers, but may also translate to the clinical depression which devastates the lives of so many people.
    Frontiers in Neurology 07/2013; 4:81. DOI:10.3389/fneur.2013.00081

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