Cross-sectional study on prevalences of psychiatric disorders in mutation carriers of Huntington's disease compared with mutation-negative first-degree relatives.
ABSTRACT 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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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 · 4.16 Impact Factor
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ABSTRACT: Background Involuntary movements, neuropsychiatric symptoms, and cognitive impairment are all part of the symptom triad in Huntington¿s disease (HD). Despite the fact that neuropsychiatric symptoms and cognitive decline may be early manifestations of HD, the clinical diagnosis is conventionally based on the presence of involuntary movements and a positive genetic test for the HD CAG repeat expansion. After investigating the frequencies of the triad manifestations in a large outpatient clinical cohort of HD gene-expansion carriers, we propose a new clinical classification.Methods In this cross-sectional study, 107 gene-expansion carriers from a Danish outpatient clinic were recruited. All participants underwent neurological examination, psychiatric evaluation and neuropsychological testing. Participants were categorised according to motor symptoms, neuropsychiatric symptoms, the use of psychotropic medication, and cognitive impairment.ResultsAmong the motor manifest HD gene-expansion carriers, 51.8% presented with the full symptom triad, 25.0% were defined as cognitively impaired in addition to motor symptoms, and 14.3% had neuropsychiatric symptoms along with motor symptoms. Only 8.9% had isolated motor symptoms. Among gene-expansion carriers without motor symptoms, 39.2% had neuropsychiatric symptoms, were cognitively impaired, or had a combination of the two.Conclusion This is the first study to report the frequencies of both motor symptoms, cognitive impairment, and neuropsychiatric symptoms in HD gene-expansion carriers in a national outpatient HD clinical cohort. We found that almost 40% of the gene-expansion carriers without motor symptoms had either neuropsychiatric symptoms, cognitive impairment or both, emphasising that these patients are not premanifest in psychiatric and cognitive terms, suggesting that the current clinical classification is neither necessarily suitable nor helpful for this patient group. Some premanifest gene-expansion carriers may have psychiatric and/or cognitive symptoms caused by reactive stress or other pathology than HD. Acknowledging this fact we, however, suggest classifying all HD gene-expansion carriers into three clinical categories: premanifest, non-motor manifest, and motor manifest.Orphanet Journal of Rare Diseases 07/2014; 9(1):114. DOI:10.1186/s13023-014-0114-8 · 3.96 Impact Factor
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ABSTRACT: Activation of the innate immune system has been postulated in the pathogenesis of Huntington's disease (HD). We studied serum concentrations of C-reactive protein (CRP) and low albumin as positive and negative acute-phase proteins in HD. Multivariate linear and logistic regression was used to study the association between acute-phase protein levels in relation to clinical, neuropsychiatric, cognitive, and psychotropic use characteristics in a cohort consisting of 122 HD mutation carriers and 42 controls at first biomarker measurement, and 85 HD mutation carriers and 32 controls at second biomarker measurement. Significant associations were found between acute-phase protein levels and Total Functioning Capacity (TFC) score, severity of apathy, cognitive impairment, and the use of antipsychotics. Interestingly, all significant results with neuropsychiatric symptoms disappeared after additional adjusting for antipsychotic use. High sensitivity CRP levels were highest and albumin levels were lowest in mutation carriers who continuously used antipsychotics during follow-up versus those that had never used antipsychotics (mean difference for CRP 1.4 SE mg/L; P=0.04; mean difference for albumin 3 SE g/L; P<0.001). The associations found between acute-phase proteins and TFC score, apathy, and cognitive impairment could mainly be attributed to the use of antipsychotics. This study provides evidence that HD mutation carriers who use antipsychotics are prone to develop an acute-phase response.European Neuropsychopharmacology 08/2014; 24(8). DOI:10.1016/j.euroneuro.2014.05.004 · 5.40 Impact Factor