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. 2021 Aug 3;16(1):340.
doi: 10.1186/s13023-021-01967-2.

Endophenotypical drift in Huntington's disease: a 5-year follow-up study

Marie N N Hellem  1 , Rebecca K Hendel  2   3 , Tua Vinther-Jensen  2   4 , Ida U Larsen  4 , Troels T Nielsen  2 , Lena E Hjermind  2 , Esben Budtz-Jørgensen  5 , Asmus Vogel  2   3 , Jørgen E Nielsen  2
Affiliations

Endophenotypical drift in Huntington's disease: a 5-year follow-up study

Marie N N Hellem et al. Orphanet J Rare Dis. .

Abstract

Background: Huntington's disease (HD) is clinically characterized by progressing motor, cognitive and psychiatric symptoms presenting as varying phenotypes within these three major symptom domains. The disease is caused by an expanded CAG repeat tract in the huntingtin gene and the pathomechanism leading to these endophenotypes is assumed to be neurodegenerative. In 2012/2013 we recruited 107 HD gene expansion carriers (HDGECs) and examined the frequency of the three cardinal symptoms and in 2017/2018 we followed up 74 HDGECs from the same cohort to describe the symptom trajectories and individual drift between the endophenotypes as well as potential predictors of progression and remission.

Results: We found higher age to reduce the probability of improving on psychiatric symptoms; increasing disease burden score ((CAG-35.5) * age) to increase the risk of developing cognitive impairment; increasing disease burden score and shorter education to increase the risk of motor onset while lower disease burden score and higher Mini Mental State Examination increased the probability of remaining asymptomatic. We found 23.5% (N = 8) to improve from their psychiatric symptoms.

Conclusions: There is no clear pattern in the development of or drift between endophenotypes. In contrast to motor and cognitive symptoms we find that psychiatric symptoms may resolve and thereby not entirely be caused by neurodegeneration. The probability of improving from psychiatric symptoms is higher in younger age and advocates for a potential importance of early treatment.

Keywords: Cognitive symptoms; Endophenotype; Huntington’s disease; Psychiatric symptoms.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart used for categorization of participants into the neuropsychiatric vs. the non-neuropsychiatric groups. Psychotropic—meaning use of psychotropic medication in the motor manifest group, 4 participants did not complete the SCL-90-R, 2 received psychotropic medication and therefore classified as having psychiatric symptoms and 2 did not receive psychotropic medication and were clinically evaluated as not having psychiatric symptoms
Fig. 2
Fig. 2
Distribution of the endophenotypes in Cohort 2013 and Cohort 2018
Fig. 3
Fig. 3
Endophenotypical drift in the Baseline 2013 Cohort to Cohort 2018. Overview of the follow-up participants and their drift between phenotypes. Right side of the figure represents the Manifest group (subgroups marked by a Man) and the left side the Premanifest group (subgroups marked by a Pre). Both sides are vertically divided into Baseline 2013 and Cohort 2018. The cohorts are horizontally divided in to four subgroups. The zero indicates neither cognitive nor psychiatric symptoms, P means addition of psychiatric symptoms, C addition of cognitive symptoms and PC addition of both cognitive and psychiatric symptoms. The number indicates the HDGECs in the group and the arrows show the drift from Baseline 2013
See this image and copyright information in PMC

References

    1. Ghosh R, Tabrizi SJ. Clinical Aspects of Huntington’s Disease. In: Geyer MA, Ellenbroek BA, Marsden CA, Barnes TRE, Nguyen HHP, Cenci MA, editors. Behavioral Neurobiology of Huntington’s Disease and Parkinson’s Disease. Berlin: Springer Berlin Heidelberg; 2013. p. 3–31.
    1. Goh AMY, Wibawa P, Loi SM, Walterfang M, Velakoulis D, Looi JCL. Huntington’s disease: neuropsychiatric manifestations of Huntington’s disease. Australas Psychiatry. 2018;26(4):366–375. doi: 10.1177/1039856218791036. - DOI - PubMed
    1. Vinther-Jensen T, Nielsen TT, Budtz-Jørgensen E, Larsen IU, Hansen MM, Hasholt L, et al. Psychiatric and cognitive symptoms in Huntington’s disease are modified by polymorphisms in catecholamine regulating enzyme genes. Clin Genet. 2016;89(3):320–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26081309. - PubMed
    1. van Duijn E, Kingma E, van der Mast MR. Psychopathology in verified Huntington’s disease gene carriers. J Neuropsychiatry Clin Neurosci [Internet]. 2007;19(4):441–448. doi: 10.1176/jnp.2007.19.4.441. - DOI - PubMed
    1. Ross CA, Aylward EH, Wild EJ, Langbehn DR, Long JD, Warner JH, et al. Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat Publ Gr. 2014;10(1110):204–216. - PubMed

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