Neuropsychiatric View of Huntington‘s Disease

Czech version

Authors: J. Necpál ¹; M. Patarák ²
Authors‘ workplace: Neurologické oddelenie, Nemocnica Zvolen a. s. ¹; Psychiatrické oddelenie, FNsP F. D. Roosevelta Banská Bystrica ²
Published in: Cesk Slov Neurol N 2013; 76/109(4): 438-445
Category: Review Article

Overview

Huntington’s disease is a progressive and fatal neurodegenerative disorder with an incidence of about 5 cases per 100,000 people. There is familial occurrence, with autosomal dominant inheritance. The more family members affected, the greater the burden these families have. A typical phenotype is choreatic hyperkinesia, though rigidity, hypokinesia and gait disturbance appear years later. Cognitive and psychiatric symptoms are typical, often preceding clinical expression of movement disorders. From the clearly defined genotype, a trio of pathological symptoms grows, with considerable phenomenological polymorphic variations from individual to individual. Psychiatric disorders often impair the quality of life more than motor abnormalities and can lead to suicide, the second leading cause of death in individuals with Huntington’s disease. Therefore, the neuropsychiatric view of this disease is not just a quantitative synthesis of findings from neurology and psychiatry, but rather an integral and comprehensive approach is also taken, allowing both a better understanding of the pathogenesis and a mostly superior therapeutic approach that takes into account several aspects of the multifaceted suffering endured by these patients. The article presents an overview of the theory from a neuropsychiatric perspective on Huntington’s disease, as well as two short case studies of patients – siblings who have the disease.

Key words:
Huntington’s disease – chorea – depression –suicide – dementia – executive dysfunction

Sources

1. Heathfield KW. Huntington’s chorea: a centenary review. Postrgrad Med J 1973; 49(567): 32– 45.

2. Roos RA. Huntington’s disease: a clinical review. Orphanet J Rare Dis 2010; 5(1): 40.

3. Fahn S, Jankovic J. Principles and practice of movement disorders. Philadelphia: Churchill Livingstone Elsevier 2007.

4. Novak MJ, Tabrizi SJ. Huntington’s disease. BMJ 2010; 340: c3109.

5. Margolis RL, Ross CA. Diagnosis of Huntington’s disease. Clinical Chemistry 2003; 49(10): 1726– 1732.

6. Kosinski CM, Landwehrmeyer B. Huntington’s disease. In: Beal MF, Lang AE, Ludolph A (eds). Neurogenerative Diseases. Neurobiology, Pathogenesis and Therapeutics. New York: Cambridge University Press 2005.

7. Mascalchi M, Lolli F, Della Nave R, Tessa C, Petralli R, Gavazzi C et al. Huntington disease: volumetric, diffusion‑ weighted, and magnetization transfer MR imaging of brain. Radiology 2004; 232(3): 867– 873.

8. Montoya A, Price BH, Menear M, Lepage M. Brain imaging and cognitive dysfunctions in Huntington’s disease. J Psychiatry Neurosci 2005; 31(1): 21– 29.

9. Ross CA, Margolis RL. Huntington disease. In: Davis KL, Chamey D, Coyle JT, Nemeroff C (eds). Neuropsychopharmacology: The Fifth Generation of Progress. 1st ed. Philadelphia: Lippincott Williams Wilkins 2002.

10. Eidelberg D, Surmeier D J. Brain networks in Huntington disease. J Clin Invest 2011; 121(2): 484– 492.

11. Wolker FO. Huntington’s disease. Lancet 2007; 369(9557): 218– 228.

12. Waldvogel HJ, Thu D, Hogg V, Tippett L, Faull RLM. Selective neurodegeneration, neuropathology and symptom profiles in Huntington‘s disease. In: Hannan AJ (ed). Tandem Repeat Polymorphisms: Genetic Plasticity, Neural Diversity and Disease. New York: Landes Bioscience and Springer Science+Business Media 2012.

13. Patarák M. Huntingtonova choroba: neuropsychiatrické aspekty [on‑line]. I‑ med 2012. Available from: http:/ / www.i‑ med.sk/ moodle/ course/ category.php?id=921&druh_specializacii=1.

14. Rosenblatt A. Neuropsychiatry of Huntington’s disease. Dialogues Clin Neurosci 2007; 9(2): 191– 197.

15. Duff K, Paulsen JS, Beglinger LJ, Langbehn DR, Wang C, Stout JC et al. “Frontal” behaviors before the diagnosis of Huntington’s disease and their relationship to markers of disease progression: evidence of early lack of awareness. J Neuropsychiatry Clin Neurosci 2010; 22(2): 196– 207.

16. Craufurd D, Snowden J. Neuropsychological and neuropsychiatric aspects of Huntington’s disease. In: Bates G, Harper P, Jones L (eds). Huntington’s disease. New York: Oxford University Press 2002: 62– 94.

17. Allain P, Gaura V, Fasotti L, Chauviré V, Prundean A,Sherer‑ Gagou C et al. The neural substrates of script knowledge deficits as revealed by a PET study in Huntington’s Disease. Neuropsychologia 2011; 49(9): 2673– 2684.

18. Grahn J, Parkinson JA, Owen AM. The role of the basal ganglia in learning and memory: Neuropsychological studies. Behav Brain Res 2009; 199(1): 53– 60.

19. Duff K, Paulsen J, Mills J, Beglinger LJ, Moser DJ, Smith MM et al. Mild cognitive impairment in prediagnosed Huntington disease. Neurology 2010; 75(6): 500– 507.

20. Eddy CM, Mitchell IJ, Beck SR, Cavanna AE, Rickards HE. Altered subjective fear responses in Huntington’s disease. Parkinsonism Relat Disord 2011; 17(5): 386– 389.

21. Illea R, Hollb AK, Kapfhammerb HP, Reisingerb K, Schafera A, Schienlea A. Emotion recognition and experience in Huntington‘s disease: Is there a differential impairment? Psychiatry Res 2011; 188(3): 377– 382.

22. Klöppel S, Stonnington CS, Petrovic P, Mobbs D, Tuscher O, Craufurd D et al. Irritability in pre‑clinical Huntington‘s disease. Neuropsychologia 2010; 48(2): 549– 557.

23. Sachdev PS. Huntington’s Disease and related disorders and their association with schizophrenialike psychosis. In: Sachdev PS, Keshavan MS (eds). Secondary Schizophrenia. Cambridge: Cambridge University Press 2010: 348– 357.

24. Van Duijn E, Reedeker N, Giltay EJ, Roos RAC, Van der Mast RC. Correlates of apathy in Huntington’s disease. J Neuropsychiatry Clin Neurosci 2010; 22(3): 287– 294.

25. Eslava JC, Iragorri‑ Cucalón Á, Ucrós‑ Rodríguez G,Bonilla‑ Jácome C, Tovar‑ Perdomo S, Herin DV et al. Obsessive‑ Compulsive Disorder Symptoms in Huntington’s Disease: A Case Report. Rev Colomb Psiquiatr 2008; 37(4): 644– 654.

26. Anderson KE, Louis ED, Stern Y, Marder KS. Cognitive correlates of obsessive and compulsive symptoms in Huntington’s disease. Am J Psychiatry 2001; 158(5): 799– 801.

27. Uhlmann WR. The Woman Who Walked into the Sea: Huntington’s and the Making of a Genetic Disease. American J Hum Genet 2010; 86(6): 830– 831.

28. Wexler A. The art of medicine. Stigma, history, and Huntington’s disease. Lancet 2010; 376(9734): 18– 19.

29. Penarand E, Garcia A, Montgomery L. It wasn’t Witchcraft – It was Huntington Disease! J Am Board Fam Med 2011; 24(1): 115– 116.

30. Paulsen JS, Hoth KF, Nehl C, Stierman L, The Huntington Study Group. Critical Periods of Suicide Risk in Huntington’s Disease. Am J Psychiatry 2005; 162(4): 725– 731.

31. Pang TYC, Du X, Zajac MS, Howard M, Hannan AJ. Altered serotonin receptor expression is associated with depression‑related behavior in the R6/ 1 transgenic mouse model of Huntington’s disease. Hum Mol Genet 2009; 18(4): 753– 766.

32. Gudesblatt M, Tarsy D. Huntington’s Disease: A Clinical Review. Supplement to Neurology Reviews 2011; 1– 8.

33. Perlis RH, Smolier JW, Mysore J, Sun M, Gillis T, Purcell S et al. Prevalence of incompletely penetrant Huntington’s disease alleles among individuals with major depressive disorder. Am J Psychiatry 2010; 167(5): 574– 579.

34. Krogias C, Strassburger K, Eyding J, Gold R, Norra C,Juckel G et al. Depression in patients with Huntington disease correlates with alterations of the brain stem raphe depicted by transcranial sonography. Psychiatry Neurosci 2011; 36(3): 187– 194.

35. Saleh N, Moutereau S, Durr A, Krystkowiak P, Azulay JP, Tranchant C et al. Neuroendocrine Disturbances in Huntington’s Disease. PLoS ONE 2009; 4(3): e4962.

36. Peng Q, Masuda N, Jiang M, Li Q, Zhao M, Ross CA et al. The antidepressant sertraline improves the phenotype, promotes neurogenesis and increases BDNF levels in the R6/ 2 Huntington’s disease mouse model. Exp Neurol 2008; 210(1): 154– 163.

37. Walker TL, Turnbull GF, Mackay EW, Hannan AJ, Barlett PF. The latent stem cell population is retained in the hippocampus of transgenic Huntington’s disease mice but not wild‑type mice. PLoS One 2011; 6(3): e18153.

38. Zuccato C, Cattaneo E. Role of brain‑derived neurotrophic factor in Huntington’s disease. Prog Neurobiol 2007; 81(5– 6): 294– 330.

39. Petersén A, Bjőrkqvist M. Hypothalamic‑ endocrine aspects in Huntington’s disease. Eur J Neurosci 2006; 24(4): 961– 967.

40. Petersén A, Gil J, Maat‑ Schieman ML, Bjőrkqvist M, Tanila H, Araujo IM et al. Orexin loss in Huntington’s disease. Hum Mol Genet 2005; 14(1): 39– 47.

41. Farrer LA. Diabetes mellitus in Huntington’s disease. Clin Genet 1985; 27(1): 62– 67.

42. Lalić NM, Marić J, Svetel M, Jotić A, Stefanova E, Lalić K, et al. Glucose homeostasis in Huntington Disease. Abnormalities in Insulin Sensitivity and Early‑ Phase Insulin Secretion. Arch Neurol 2008; 65(4): 476– 480.

43. Squitieri F, Frati L, Ciarmiello A, Lastoria S, Quarell O.Juvenile Huntington’s fisease: foes a dosage‑ effect pathogenic mechanism differ from the classical adult disease? Mech Ageing Dev 2006; 127(2): 208– 212.

44. Nance M, Jones R, Imbriglio S, Gettig B. The Juvenile Huntington’s Disease Handbook. A Guide for Physicians, Neurologists and Other Professionals. New York: Huntington’s Disease Society of America 2001.

45. International Huntington Association (IHA) and the World Federation of Neurology (WFN) Research Group on Huntington’s Chorea. Guidelines for the molecular genetics predictive test in Huntington’s disease. Neurology 1994; 44(8): 1533– 1536.

46. International Huntington Association (IHA) and the World Federation of Neurology (WFN) Research Group on Huntington’s Chorea. Guidelines for the molecular genetics predictive test in Huntington’s disease. J Med Genet 1994; 31(7): 555– 559.

47. Roth J. Huntingtonova nemoc. Cesk Slov Neurol N 2010; 73/ 106(2): 107– 123.

48. Židovská J, Klempíř J, Kebrdlová V, Uhrová T, Koblihová J, Anders M et al. Huntingtonova nemoc: zkušenosti s genetickým testováním v letech 1994– 2005. Cesk Slov Neurol N 2007; 70/ 103(1): 72– 77.

49. Douaud G, Gaura V, Ribeiro M‑ J, Lethimonnier F,Maroy R, Verny C et al. Distribution of grey mater atrophy in Huntington’s disease patients: a combined ROI‑based and voxel‑based morphometric study. Neuroimage 2006; 32(4): 1562– 1575.

50. Huntington Study Group. Unified Huntington’s Disease Rating Scale: Reliability and Consistency. Mov Disorders 1996; 11(2): 136– 142.

51. Frank S. Tetrabenazine as anti‑chorea therapy in Huntington disease: an open label continuation study. Huntington Study Group/ TETRA‑ HD Investigators. BMC Neurol 2009; 9: 62.

52. Venuto C S, McGarry A, Ma Q, Kiebutz K. Pharmacologic approaches to the treatment of Huntington’s disease. Mov Disord 2012 27(1): 31– 41.

53. Kenney C, Hunter C, Davidson A, Jankovic J. Short‑term effects of tetrabenazine on chorea associated with Huntington’s disease. Mov Disord 2007; 22(1): 10– 13.

54. Paleacu D, Anca M, Giladi N. Olanzapine in Huntington’s disease. Acta Neurol Scand 2002; 105(6): 441– 444.

55. Lundin A, Dietrichs E, Haghighi S, Göller ML, Heiberg A, Loutfi G et al. Efficacy and safety of the dopaminergic stabilizer Pridopidine (ACR16) in patients with Huntington’s disease. Clin Neuropharmacol 2010; 33(5): 260– 264.

56. Huntington Study Group. A randomized, placebo‑ controlled trial of coenzyme Q10 and remacemide in Huntington’s disease. Neurology 2001; 57(3): 397– 404.

57. Kanazawa I. Therapeutic strategies in Huntington’s Disease. J Clin Neurol 2006; 2(4): 213– 224.

58. Bachoud‑ Lévi AC, Rémy P, Nguyen JP, Brugières P, Lefaucheur JP, Bourdet C et al. Motor and cognitive improvements in patients with Huntington’s disease after neural transplantation. Lancet 2000; 356(9246): 1975– 1979.