|Year : 2021 | Volume
| Issue : 1 | Page : 1-3
Huntington’s disease—not just a disease of brain but mind as well!!
Anjali Chouksey1, Sanjay Pandey2
1 Department of Neurology, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Neurology, Govind Ballabh Pant Postgraduate Institute of Medical Education and Research, New Delhi, India
|Date of Submission||30-Mar-2021|
|Date of Acceptance||03-Apr-2021|
|Date of Web Publication||17-Apr-2021|
Dr. Sanjay Pandey
Department of Neurology, Academic Block, Room no. 503, Govind Ballabh Pant Postgraduate Institute of Medical Education and Research, New Delhi.
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Chouksey A, Pandey S. Huntington’s disease—not just a disease of brain but mind as well!!. Ann Mov Disord 2021;4:1-3
|How to cite this URL:|
Chouksey A, Pandey S. Huntington’s disease—not just a disease of brain but mind as well!!. Ann Mov Disord [serial online] 2021 [cited 2023 Mar 23];4:1-3. Available from: https://www.aomd.in/text.asp?2021/4/1/1/313933
Huntington’s disease (HD) is a neurodegenerative disorder with autosomal dominant inheritance resulting from an expanded CAG repeats in the Huntingtin gene on chromosome 4p. It is characterized by a triad of motor, cognitive, and psychiatric disturbances. Most of the clinical descriptions and research work in HD have emphasized the overwhelming motor symptoms dominating at the time of diagnosis. However, the psychiatric disturbances associated with HD deserve equal attention as they often begin early in the course of the disease and significantly impact the quality of life and caregiver burden. Even the original description of HD in George Huntington’s paper in 1972 mentions the “tendency to insanity” as one of the distinctive features of this subgroup of chorea. In the review article published in this issue of Annals of Movement Disorder, Raju et al. mentioned the ancient Indian descriptions of possible Huntington’s disease as “Tandavaroga” in the Ayurvedic literature. The neuropsychiatric symptoms of this condition has also been described in the Sharangadhara Samhita as Adhirah (disturbed intellect) and Prana Vatavikruti (behavioral change). In 1925, Hughes found that around 42% of his 172 affected HD cases had “temperamental irregularities” in the form of easily excited, shrewish, inconsistent, seclusive, stubborn, and uninhibited display of eroticism. In the early part of 20 century, these patients were often misdiagnosed, leading to admission to the asylum because of the early prominent psychiatric symptoms in their pre-choreic stage of the disease. With the increasing understanding of neuronal networks involved in the control of movement, cognition, emotion, behavior, and enhancing knowledge of pathophysiology of HD, the importance of the neuropsychiatric aspect of HD has been increasingly realized, and many attempts have been made to address it.
Several studies have confirmed the high prevalence of neuropsychiatric symptoms in preclinical stages of HD, and thus they can serve as the earliest marker of the disease., Unlike motor symptoms, most of the psychiatric symptoms do not follow the disease course and can wax and wane. Although they are non-specific and not seen in all HD patients, they are often considered significantly bothersome by caregivers when present. The commonly reported psychiatric symptoms in HD patients include apathy, irritability, anxiety, and depression. The point prevalence of apathy in HD varies from 34–76%, and it is more likely to be associated with male gender, older age, and psychotropic medication use intake. Unlike other psychiatric symptoms, only apathy shows a linear correlation with the neurodegenerative process of HD as it increases linearly with motor, cognitive, and functional markers of disease progression. Thus, it can be considered as a core psychiatric symptom of HD.
Depression is one of the earliest psychiatric symptoms seen in HD and may precede the onset of motor symptoms by years. The prevalence of depression varies across HD stages, peaking during the early stages of the disease followed by gradual reduction as the disease progresses into the later stages. At advanced HD stages, cognitive decline causes diminished subjective awareness of depression, resulting in its declining incidence. Depression can be associated with an increased risk of suicide in HD patients, particularly during two critical periods of susceptibility—the prodromal phase and stage 2, i.e., when their functional independence starts to compromise. Different studies showed that 7–10% of HD patients consider or attempt suicide during their disease course.
Irritability, including excess anger, aggression, and poor temper control, is one of the common behavioral disturbance observed in HD, inevitably affecting the interpersonal relationship. Its prevalence in HD range between 35% and 73%. Psychosis has been reported as a less common psychiatric manifestation of HD, with a lifetime prevalence of 10.4% in this population, compared with 3.48–11.6% in the general population. Its prevalence is thought to be underestimated in HD because of small/limited series evaluating psychosis in HD, masking milder psychotic symptoms due to the treatment with antipsychotic medications taken for motor symptoms or irritability, and the limited ability of psychotic patients to participate in trials. However, a recent study suggested that the HD patients with psychosis may represent a unique phenotype in the HD spectrum as they found that the psychosis was associated with a lower number of CAG repeats and younger age at a clinical diagnosis of HD.
Different studies tried to correlate the psychiatric symptoms of HD with the number of CAG repeats. An inverse relationship between the CAG repeats length and the age of onset has been observed, with those having longer CAG repeats tend to have an earlier onset. Recent data suggest that apart from CAG repeat length, age at clinical onset is modified by other environmental factors, cellular aging and various ageing-related genes, which also plays a vital role in inducing the disease-specific phenotypes in HD patients., Most of the studies failed to prove any significant correlation between the CAG repeat length and likelihood or severity of psychiatric symptoms in HD., However, one recent study found that the likelihood of irritability and depression reduced significantly with longer CAG length.
There is a significant degree of heterogeneity in the prominence and evolution of motor and psychiatric symptoms seen in HD despite its monogenic nature. One of the proposed reasons for this heterogeneity includes a variable degree of neurodegenerative changes seen in different neural circuits. A recent study using multimodal neuroimaging approaches found that cognitive and motor symptoms in HD shared a common neurobiological basis and were associated with gray matter regions and white matter tracts. In contrast, the psychiatric domain presented a differentiated neural signature and was mainly related to cortical areas and white matter tracts associated with emotional processing. In this issue of Annals of Movement Disorder, Kamble et al. has published their work where they utilized advanced neuroimaging techniques to delineate the neural substrate involved in the pathophysiology of psychiatric symptoms in patients with HD. Their study suggest that in addition to caudate atrophy, HD patients with psychiatric disturbance also has some atrophy in the hypothalamus, right precuneus, superior temporal gyrus, globus pallidus, and left culmen and also the involvement of cerebral white matter and thalamus.
Currently, there is no effective disease-modifying therapy available for HD patients. Thus, treatments primarily consist of pharmacological strategies to alleviate the motor and non-motor symptoms in HD. Both the clinicians and researcher need to further focus their attention on the psychiatric symptoms in HD. Understanding the clinical heterogeneity and its neurobiological correlation in HD will help define specific biomarkers that can predict the symptom profile, even during subclinical stages. It would also help to individualize treatments that targets explicitly one specific symptom domain.
Financial support and sponsorship
No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Huntington G. On chorea. Med Surg Rep 1872;26:317-21.
Srinivas Raju, Prashanth Kukkle. Huntington’s disease: The Indian perspective. Ann Mov Disord 2021;4:4-9.
Hughes EM. Social significance of Huntington’s chorea. Am J Psychiatr 1925;4:537-74.
Epping EA, Kim J-I, Craufurd D, Brashers-Krug TM, Anderson KE, et al
. Longitudinal psychiatric symptoms in prodromal Huntington’s disease: A decade of data. Am J Psychiatr 2016;173:184-92.
Martinez-Horta S, Perez-Perez J, van Duijn E, Fernandez-Bobadilla R, Carceller M, Pagonabarraga J, et al
. Neuropsychiatric symptoms are very common in premanifest and early stage Huntington’s disease. Parkinson Relat Dis 2016;25: 58-64.
Van Duijn E, Reedeker N, Giltay EJ, Roos RAC, van der Mast RC. Correlates of apathy in Huntington’s disease. J Neuropsychiatr Clin Neurosci 2010;22:287-94.
Paulsen JS, Nehl C, Hoth KF, Kanz JE, Benjamin M, Conybeare R, et al
. Depression and stages of Huntington’s disease. J Neuropsychiatr Clin Neurosci 2005;17:496-502.
Eddy CM, Parkinson EG, Rickards HE. Changes in mental state and behaviour in Huntington’s disease. Lancet Psychiatr 2016;3:1079-86.
Rocha NP, Mwangi B, Gutierrez Candano CA, Sampaio C, Furr Stimming E, Teixeira AL. The clinical picture of psychosis in manifest Huntington’s disease: A comprehensive analysis of the enroll-HD database. Front Neurol 2018;9:930.
Genetic Modifiers of Huntington’s Disease (GeM-HD) Consortium. CAG repeat not polyglutamine length determines timing of Huntington’s disease onset. Cell 2019;178:887-900.
Huntington’s GM of Disease Consortium (GeM-HD). Identification of genetic factors that modify clinical onset of Huntington’s disease. Cell 2015;162:516-26.
Zappacosta B, Monza D, Meoni C, Austoni L, Soliveri P, Gellera C, et al
. Psychiatric symptoms do not correlate with cognitive decline, motor symptoms, or CAG repeat length in Huntington’s disease. Arch Neurol1996;53:493-7.
Berrios GE, Wagle AC, Markova IS, Wagle SA, Ho LW, Rubinsztein DCet al
. Psychiatric symptoms and CAG repeats in neurologically asymptomatic Huntington’s disease gene carriers. Psychiatr Res 2001;102:217-25.
Ellis N, Tee A, McAllister B, Massey T, McLauchlan D, Stone T, et al
. Genetic risk underlying psychiatric and cognitive symptoms in Huntington’s disease. Biol Psychiatr 2020;87:857-65.
Garcia-Gorro C, Llera A, Martinez-Horta S, Perez-Perez J, Kulisevsky J, Rodriguez-Dechicha N, et al
. Specific patterns of brain alterations underlie distinct clinical profiles in Huntington’s disease. Neuroimage Clin 2019;23:101900.
Nitish Kamble, Jitender Saini, Lija George, Nikhil Ratna, Amitabh Bhattacharya, Ravi Yadav, et al
. Neural substrates of psychiatric symptoms in patients with Huntington’s disease. Ann Mov Disord 2021;4:21-7.