Skip to main content

Advertisement

Springer Nature Link
Log in

Substance abuse may be a risk factor for earlier onset of Huntington disease

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Environmental factors may contribute as much as one-third of the variance in Huntington disease (HD) age of onset. Substance abuse is a risk factor for other neurodegenerative disorders; however, whether substance abuse influences HD age of onset is not well established. This study investigated the relationships between alcohol, drug, and tobacco abuse and HD age of onset in 136 participants with symptomatic HD. CAG repeat length was used as a covariate in all analyses, as it represents the most significant determinant of HD age of onset. The relationship between substance abuse, HD age of onset, and sex was also examined, as women may experience greater medical harm from substance abuse. Lifetime alcohol abuse and lifetime drug abuse were associated with earlier age of HD onset; a similar trend was seen for current tobacco abuse. For women, lifetime alcohol abuse was associated with earlier onset of HD, with a similar trend for lifetime drug abuse. However, alcohol, drug, and tobacco abuse were not significantly associated with age of onset in men. Further work is needed to determine whether substance abuse is a causative risk factor for earlier onset of HD, and why the environmental factors associated with age of onset vary by sex.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Wexler NS, Lorimer J, Porter J, Gomez F, Moskowitz C, Shackell E et al (2004) Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington’s disease age of onset. Proc Natl Acad Sci USA 101:3498–3503

    Article  PubMed  CAS  Google Scholar 

  2. Ascherio A, Munger KL (2007) Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Ann Neurol 61:504–513

    Article  PubMed  CAS  Google Scholar 

  3. Reitz C, den Heijer T, van Duijn C, Hofman A, Breteler MM (2007) Relation between smoking and risk of dementia and Alzheimer disease: the Rotterdam Study. Neurology 69:998–1005

    Article  PubMed  CAS  Google Scholar 

  4. Harwood DG, Kalechstein A, Barker WW, Strauman S, St George-Hyslop P, Iglesias C et al (2009) The effect of alcohol and tobacco consumption, and apolipoprotein E genotype, on the age of onset in Alzheimer’s disease. Int J Geriatr Psychiatry 25:511–518

    Article  Google Scholar 

  5. Sabia S, Marmot M, Dufouil C, Singh-Manoux A (2008) Smoking history and cognitive function in middle age from the Whitehall II study. Arch Intern Med 168:1165–1173

    Article  PubMed  Google Scholar 

  6. Chen H, Huang X, Guo X, Mailman RB, Park Y, Kamel F et al (2010) Smoking duration, intensity, and risk of Parkinson disease. Neurology 74:878–884

    Article  PubMed  CAS  Google Scholar 

  7. Thomas VS, Rockwood KJ (2001) Alcohol abuse, cognitive impairment, and mortality among older people. J Am Geriatr Soc 49:415–420

    Article  PubMed  CAS  Google Scholar 

  8. Robbins TW, Ersche KD, Everitt BJ (2008) Drug addiction and the memory systems of the brain. Ann NY Acad Sci 1141:1–21

    Article  PubMed  CAS  Google Scholar 

  9. Buruma OJ, Van der Kamp W, Barendswaard EC, Roos RA, Kromhout D, Van der Velde EA (1987) Which factors influence age at onset and rate of progression in Huntington’s disease? J Neurol Sci 80:299–306

    Article  PubMed  CAS  Google Scholar 

  10. Myers RH, Sax DS, Koroshetz WJ, Mastromauro C, Cupples LA, Kiely DK et al (1991) Factors associated with slow progression in Huntington’s disease. Arch Neurol 48:800–804

    Article  PubMed  CAS  Google Scholar 

  11. Ehret JC, Day PS, Wiegand R, Wojcieszek J, Chambers RA (2007) Huntington disease as a dual diagnosis disorder: data from the National Research Roster for Huntington disease patients and families. Drug Alcohol Depend 86:283–286

    Article  PubMed  Google Scholar 

  12. Friedman JH, Trieschmann ME, Myers RH, Fernandez HH (2005) Monozygotic twins discordant for Huntington disease after 7 years. Arch Neurol 62:995–997

    Article  PubMed  Google Scholar 

  13. Palmer RH, Young SE, Hopfer CJ, Corley RP, Stallings MC, Crowley TJ et al (2009) Developmental epidemiology of drug use and abuse in adolescence and young adulthood: evidence of generalized risk. Drug Alcohol Depend 102:78–87

    Article  PubMed  Google Scholar 

  14. Zilberman M, Tavares H (2003) el-Guebaly N. Gender similarities and differences: the prevalence and course of alcohol- and other substance-related disorders. J Addict Dis 22:61–74

    Article  PubMed  Google Scholar 

  15. Hernandez-Avila CA, Rounsaville BJ, Kranzler HR (2004) Opioid-, cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment. Drug Alcohol Depend 74:265–272

    Article  PubMed  CAS  Google Scholar 

  16. Becker JB, Hu M (2008) Sex differences in drug abuse. Front Neuroendocrinol 29:36–47

    Article  PubMed  CAS  Google Scholar 

  17. Hommer D, Momenan R, Kaiser E, Rawlings R (2001) Evidence for a gender-related effect of alcoholism on brain volumes. Am J Psychiatry 158:198–204

    Article  PubMed  CAS  Google Scholar 

  18. Mann K, Ackermann K, Croissant B, Mundle G, Nakovics H, Diehl A (2005) Neuroimaging of gender differences in alcohol dependence: are women more vulnerable? Alcohol Clin Exp Res 29:896–901

    Article  PubMed  CAS  Google Scholar 

  19. Paul CA, Au R, Fredman L, Massaro JM, Seshadri S, Decarli C et al (2008) Association of alcohol consumption with brain volume in the Framingham study. Arch Neurol 65:1363–1367

    Article  PubMed  Google Scholar 

  20. Mucha L, Stephenson J, Morandi N, Dirani R (2006) Meta-analysis of disease risk associated with smoking, by gender and intensity of smoking. Gend Med 3:279–291

    Article  PubMed  Google Scholar 

  21. van der Plas EA, Crone EA, van den Wildenberg WP, Tranel D, Bechara A (2009) Executive control deficits in substance-dependent individuals: a comparison of alcohol, cocaine, and methamphetamine and of men and women. J Clin Exp Neuropsychol 31:706–719

    Article  PubMed  Google Scholar 

  22. Pekmezovic T, Svetel M, Maric J, Dujmovic-Basuroski I, Dragasevic N, Keckarevic M et al (2007) Survival of Huntington’s disease patients in Serbia: longer survival in female patients. Eur J Epidemiol 22:523–526

    Article  PubMed  Google Scholar 

  23. Foroud T, Gray J, Ivashina J, Conneally PM (1999) Differences in duration of Huntington’s disease based on age at onset. J Neurol Neurosurg Psychiatry 66:52–56

    Article  PubMed  CAS  Google Scholar 

  24. Bode FJ, Stephan M, Suhling H, Pabst R, Straub RH, Raber KA et al (2008) Sex differences in a transgenic rat model of Huntington’s disease: decreased 17beta-estradiol levels correlate with reduced numbers of DARPP32 + neurons in males. Hum Mol Genet 17:2595–2609

    Article  PubMed  CAS  Google Scholar 

  25. Dorner JL, Miller BR, Barton SJ, Brock TJ, Rebec GV (2007) Sex differences in behavior and striatal ascorbate release in the 140 CAG knock-in mouse model of Huntington’s disease. Behav Brain Res 178:90–97

    Article  PubMed  CAS  Google Scholar 

  26. Hasin DS, Stinson FS, Ogburn E, Grant BF (2007) Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States: results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry 64:830–842

    Article  PubMed  Google Scholar 

  27. Compton WM, Thomas YF, Stinson FS, Grant BF (2007) Prevalence, correlates, disability, and comorbidity of DSM-IV drug abuse and dependence in the United States: results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry 64:566–576

    Article  PubMed  Google Scholar 

  28. Zuccato C, Cattaneo E (2007) Role of brain-derived neurotrophic factor in Huntington’s disease. Prog Neurobiol 81:294–330

    Article  PubMed  CAS  Google Scholar 

  29. Davis MI (2008) Ethanol-BDNF interactions: still more questions than answers. Pharmacol Ther 118:36–57

    Article  PubMed  CAS  Google Scholar 

  30. Yeom M, Shim I, Lee HJ, Hahm DH (2005) Proteomic analysis of nicotine-associated protein expression in the striatum of repeated nicotine-treated rats. Biochem Biophys Res Commun 326:321–328

    Article  PubMed  CAS  Google Scholar 

  31. Kenny PJ, File SE, Rattray M (2000) Acute nicotine decreases, and chronic nicotine increases the expression of brain-derived neurotrophic factor mRNA in rat hippocampus. Brain Res Mol Brain Res 85:234–238

    Article  PubMed  CAS  Google Scholar 

  32. Russo SJ, Mazei-Robison MS, Ables JL, Nestler EJ (2009) Neurotrophic factors and structural plasticity in addiction. Neuropharmacology 56(Suppl 1):73–82

    Article  PubMed  CAS  Google Scholar 

  33. Bezprozvanny I (2009) Calcium signaling and neurodegenerative diseases. Trends Mol Med 15:89–100

    Article  PubMed  CAS  Google Scholar 

  34. Lee AM, Messing RO (2008) Protein kinases and addiction. Ann NY Acad Sci 1141:22–57

    Article  PubMed  CAS  Google Scholar 

  35. Grant BF, Hasin DS, Chou SP, Stinson FS, Dawson DA (2004) Nicotine dependence and psychiatric disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry 61:1107–1115

    Article  PubMed  Google Scholar 

Download references

Conflicts of interest

Dr. Beglinger, Dr. Moser, and Dr. Gonzalez-Alegre have no conflicts of interest. This study was not sponsored. Dr. Byars received an American Psychiatric Association (APA)/Lilly Resident Research Award for this manuscript; this award did not fund the study, but rather was an award for best unpublished manuscript by a psychiatry resident. APA/Lilly played no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. Dr. Nopoulos received an honorarium from Janssen as a mentor of Dr. Byars in the context of Dr. Byars receiving an APIRE/Janssen Resident Psychiatric Research Scholars grant.

Ethical standards

All human studies must state that they have been approved by the appropriate Ethics Committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

Author information

Authors and Affiliations

  1. Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, W278 GH, 200 Hawkins Drive, Iowa City, IA, 52242, USA

    Joanne A. Byars, Leigh J. Beglinger, David J. Moser & Peg Nopoulos

  2. Department of Neurology, University of Florida College of Medicine, HSC Box 100236, Gainesville, FL, 32610-0236, USA

    Joanne A. Byars

  3. Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, 3111 MERF, 375 Newton Road, Iowa City, IA, 52242, USA

    Pedro Gonzalez-Alegre & Peg Nopoulos

  4. Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    Peg Nopoulos

Authors
  1. Joanne A. Byars
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leigh J. Beglinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David J. Moser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pedro Gonzalez-Alegre
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peg Nopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joanne A. Byars.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Byars, J.A., Beglinger, L.J., Moser, D.J. et al. Substance abuse may be a risk factor for earlier onset of Huntington disease. J Neurol 259, 1824–1831 (2012). https://doi.org/10.1007/s00415-012-6415-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-012-6415-8

Keywords

Search

Navigation