Journal of Neurology

, 255:48 | Cite as

Parkinson’s disease-related disorders in the impulsive-compulsive spectrum

  • Eric Ch. Wolters
  • Ysbrand D. van der Werf
  • Odile A. van den Heuvel


In Parkinson’s disease (PD), there is increasing evidence for disorders in the impulsive-compulsive spectrum, related to the disease itself, to the pharmacological management of this disease or to both. These disorders comprise dopamine deficiency syndrome (with immediate reward seeking behaviour), dopamine dependency syndrome (with addictive behaviour), dopamine dysregulation syndrome (with both addictive behaviour and stereotyped behaviour) and impulse control disorders (such as pathological gambling, compulsive shopping, binge eating and hypersexuality). These disorders are especially seen in PD patients with young age of onset, higher doses of antiparkinsonian drugs, pre-existent or current depression, pre-existing recreational drug or alcohol use, and high novelty seeking personality traits.

Dopamine is not only implicated in voluntary movement control but also plays a significant role in the brain’s reward system and the modulation of behaviours. Therefore, most if not all drugnaïve PD patients will suffer dysphoria, leading to mild immediate reward seeking behaviour as a consequence of the striatal dopaminergic denervation. In some of these patients, during treatment, this may even lead to the intake of increasing quantities of levodopa, above those required to adequately treat motor parkinsonism, with all characteristics of a dopamine dependence syndrome. These patients may develop plastic changes in the striatal matrix leading to hyperkinesia, caused by extracellular striatal dopaminergic fluctuations due to pulsatile dopamine replacement therapy. As soon as these changes are also seen in the striatal striosomes, in the framework of a dopamine dysregulation syndrome, stereotyped behaviours (punding) may occur (supposedly due to dorsal versus ventral striatal overactivity). Finally, impulse control disorders are suggested as being pure adverse side-effects of dopamine replacement therapy. Obsessive-compulsive behaviour (caused by ventral to dorsal overactivity) so far has not been described in PD patients.

Treatment of impulse control disorders is related to the underlying pathology. In the case of an intrinsic dopamine deficiency syndrome, treatment with dopamine replacement therapy, especially levodopa, will help. In the multifactorial (intrinsic and extrinsic) dopamine dependency and dysregulation syndromes, addictive behaviour might best be helped by psychosocial strategies, and punding by continuous dopaminergic receptor stimulation (or amantadine), hypothesized to reduce the plastic changes-induced hypersensitization. The extrinsic impulse control disorders might be best treated by reducing or replacing dopamine receptor agonists.

Key words

dopamine deficiency syndrome dopamine dependency syndrome dopamine dysregulation syndrome impulse control disorders obsessive compulsive behaviour impulsive-compulsive spectrum disorders 


  1. 1.
    Aarsland D, Larsen JP, Lim NG, et al. (1999) Range of neuropsychiatric disturbances in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 67:492–496PubMedCrossRefGoogle Scholar
  2. 2.
    Alegret M, Junque C, Vendrell P, Marti MJ, Tolosa E (2001) Obsessive-compulsive symptoms in Parkinson’s disease. J Neurol Neurosurg Psychiatry 70:394–396PubMedCrossRefGoogle Scholar
  3. 3.
    Alexander GE, Crutcher MD, DeLong MR (1990) Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions. Prog Brain Res 85:119–146PubMedCrossRefGoogle Scholar
  4. 4.
    American Psychiatric Association Diagnostic and statistic manual of mental disorders (1997) 4th ed Washington: American Psychiatric PressGoogle Scholar
  5. 5.
    Bearn J, Evans A, Kelleher M, Turner K, Lees A (2004) Recognition of a dopamine replacement therapy dependence syndrome in Parkinson’s disease: a pilot study. Drug Alcohol Depend 76:305–310PubMedCrossRefGoogle Scholar
  6. 6.
    Black DW (2007)A review of compulsive buying disorder. World Psychiatry 6:14–18PubMedGoogle Scholar
  7. 7.
    Bohnen NI, Kaufer DI, Ivanco LS, et al. (2003) Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study. Arch Neurol 60:1745–1748PubMedCrossRefGoogle Scholar
  8. 8.
    Bonci A, Singh V (2006) Dopamine dysregulation syndrome in Parkinson’s disease patients: from reward to penalty. Ann Neurol 59:733–734PubMedCrossRefGoogle Scholar
  9. 9.
    Booij J, Tissingh G, Winogrodzka A, van Royen EA (1999) Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism. Eur J Nucl Med 26:171–182PubMedCrossRefGoogle Scholar
  10. 10.
    Bosboom JLW, Stoffers D, Wolters ECh (2004) Cognitive function in Parkinson’s disease. J Neural Transm 111:1303–1315PubMedCrossRefGoogle Scholar
  11. 11.
    Braak H, Del Tredici K, Rueb U, de Vos RAI, Jansen Steur ENH, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211PubMedCrossRefGoogle Scholar
  12. 12.
    Brooks JJ (2006) Imaging the dopamine system in Parkinson’s disease. In: Wolters ECh, Berendse HW, Stam CJ (eds) Mental dysfunction in Parkinson’s disease III Amsterdam: VU Medical Press, pp 247–264Google Scholar
  13. 13.
    Dodd ML, Klos KJ, Bower JH, Geda YE, Josephs KA, Ahlskog JE (2005) Pathological gambling caused by drugs used to treat Parkinson disease. Arch Neurol 62:1377–1381PubMedCrossRefGoogle Scholar
  14. 14.
    Doder M, Rabiner EA, Turjanski N, Lees AJ, Brooks DJ (2003) Tremor in Parkinson’s disease and serotonergic dysfunction: an 11C-WAY 100635 PET study. Neurology 60:601–605PubMedGoogle Scholar
  15. 15.
    Evans AH, Lees AJ (2004) Dopamine dysregulation syndrome in Parkinson’s disease. Curr Opin Neurol 17:393–398PubMedCrossRefGoogle Scholar
  16. 16.
    Evans AH, Katzenschlager R, Paviour D, et al. (2004) Punding in Parkinson’s disease: its relation to the dopamine dysregulation syndrome. Mov Disord 19:397–405PubMedCrossRefGoogle Scholar
  17. 17.
    Evans AH, Pavese N, Lawrence AD, et al. (2006) Compulsive drug use linked to sensitized ventral striatal dopamine transmission. Ann Neurol 59:852–858PubMedCrossRefGoogle Scholar
  18. 18.
    Franken IH, Booij J, Brink BW van den (2005) The role of dopamine in human addiction: from reward to motivated attention. Eur J Pharmacol 526:199–206PubMedCrossRefGoogle Scholar
  19. 19.
    Friedman JH (1994) Punding on levodopa. Biol Psychiatry 36:350–351PubMedCrossRefGoogle Scholar
  20. 20.
    Giovannoni G, O’Sullivan JD, Turner K, Manson AJ, Lees AJ (2000) Hedonistic homeostatic dysregulation in patients with Parkinson’s disease on dopamine replacement therapies. J Neurol Neurosurg Psychiatry 68:423–428PubMedCrossRefGoogle Scholar
  21. 21.
    Groenewegen HJ, Berendse HW, Wolters JG, Lohman AH (1990) The anatomical relationship of the prefrontal cortex with the striatopallidal system, the thalamus and the amygdala: evidence for a parallel organization. Prog Brain Res 85:95–116PubMedCrossRefGoogle Scholar
  22. 22.
    Groenewegen HJ, van den Heuvel OA, Cath DC, Voorn P, Veltman DJ (2003) Does an imbalance between the dorsal and ventral striatopallidal systems play a role in Tourette’s syndrome? A neuronal circuit approach. Brain Dev 25 (Suppl 1):S3–S14PubMedCrossRefGoogle Scholar
  23. 23.
    Haber SN, Fudge JL, McFarland NR (2000) Striato-nigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum. J Neurosci 20:2369–2382PubMedGoogle Scholar
  24. 24.
    Harbishettar V, Kumar Pal P, Reddy YCJ, Thennarasu K (2005) Is there a relationship between Parkinson’s disease and obsessive-compulsive disorder? Parkinsonism Relat Disord 11:85–88PubMedCrossRefGoogle Scholar
  25. 25.
    Hollander E, Wong CM (1995) Obsessive-compulsive spectrum disorders. J Clin Psychiatry 56(Suppl 4):3–6PubMedGoogle Scholar
  26. 26.
    Hollander E, Kwon JH, Stein DJ, Broatch J, Rowland CT, Himelein CA (1996) Obsessive-compulsive and spectrum disorders: overview and quality of life issues. J Clin Psychiatry 57(Suppl 8):3–6PubMedGoogle Scholar
  27. 27.
    Isaias IU, Siri C, Cilia R, Gaspari D de, Pezzo IG, Antonini A (2008) The relationship between impulsivity and impulse control disorders in Parkinson’s disease. Mov Disord 23:411–415PubMedCrossRefGoogle Scholar
  28. 28.
    Joel D, Zohar O, Afek M, Hermesh H, Lerner L, Kuperman R, Gross-Isseroff R, Weizman A, Inzelberg R (2005) Impaired procedural learning in obsessive-compulsive disorder and Parkinson’s disease, but not in major depressive disorder. Behav Brain Research 157:253–263CrossRefGoogle Scholar
  29. 29.
    Kashihara K, Imamura T (2008) Amantadine may reverse punding in Parkinson’s disease-observation in a patient. Mov Disord 23:129–130PubMedCrossRefGoogle Scholar
  30. 30.
    Klos KJ, Bower JH, Josephs KA, Matsumoto JY, Ahlskog JE (2005) Pathological hypersexuality predominantly linked to adjuvant dopamine agonist therapy in Parkinson’s disease and multiple system atrophy Parkinsonism. Relat Disord 11:381–386CrossRefGoogle Scholar
  31. 31.
    Koran LM, Faber RJ, Aboujaoude E, Large MD, Serpe RT (2006) Estimated prevalence of compulsive buying in the United States. Am J Psychiatry 163:1806–1812PubMedCrossRefGoogle Scholar
  32. 32.
    Lawrence AD, Evans AH, Lees AJ (2003) Compulsive use of dopamine replacement therapy in Parkinson’s disease: reward systems gone awry? Lancet Neurol 2:595–604PubMedCrossRefGoogle Scholar
  33. 33.
    Lawrence AJ, Blackwell AD, Barker RA, et al. (2007) Predictors of punding in Parkinson’s disease: Results from a questionnaire survey. Mov Disord 22:2339–2345PubMedCrossRefGoogle Scholar
  34. 34.
    Mamikonyan E, Siderowf AD, Duda JE, et al. (2008) Long-term follow-up of impulse control disorders in Parkinson’s disease. Mov Disord 23:75–80PubMedCrossRefGoogle Scholar
  35. 35.
    Maia AF, Pinto AS, Barbaros ER, Menezes PR, Miguel EC (2003) Obsessive-compulsive symptoms, obsessive-compulsive disorder, and related disorders in Parkinson’s disease. J Neuropsychiatry Clin Neurosci 15:371–374PubMedGoogle Scholar
  36. 36.
    McKeon A, Josephs KA, Klos KJ, Hecksel K, Bower JH, Bostwick M, Ahlskog JE (2007) Unusual compulsive behaviors primarily related to dopamine agonist therapy in Parkinson’s disease and multiple system atrophy. Pakinsonism Relat Disord 13:516–519CrossRefGoogle Scholar
  37. 37.
    Miyasaki JM, Al Hassan K, Lang AE, Voon V (2007) Punding prevalence in Parkinson’s disease. Mov Disord 22:1179–1181PubMedCrossRefGoogle Scholar
  38. 38.
    Molina JA, Sainz-Artiga MJ, Fraile A, et al. (2000) Pathologic gambling in Parkinson’s disease: a behavioral manifestation of pharmacologic treatment? Mov Disord 15:869–872PubMedCrossRefGoogle Scholar
  39. 39.
    Murai T, Muller U, Werheid K, et al. (2001) In vivo evidence for differential association of striatal dopamine and midbrain serotonin systems with neuropsychiatric symptoms in Parkinson’s disease. J Neuropsychiatry Clin Neurosci 13:222–228PubMedGoogle Scholar
  40. 40.
    Nguygen FN, Pauly RR, Okun MS, Fernandez HH (2007) Punding as a complication of brain stem stroke?: report of a case Stroke 38:1390–1392CrossRefGoogle Scholar
  41. 41.
    Ondo WG, Lai D (2008) Predictors of impulsivity and reward seeking behaviour with dopamine agonists parkinsonism. Relat Disord 14:28–32CrossRefGoogle Scholar
  42. 42.
    O’Sullivan SS, Evans AH, Lees AJ (2007) Punding in Parkinson’s disease. Practical Neurology 7:397–399PubMedCrossRefGoogle Scholar
  43. 43.
    Potenza MN, Voon V, Weintraub D (2007) Drug insight: impulse control disorders and dopamine therapies in Parkinson’s disease. Nature Clin Pract Neurol 3:664–672CrossRefGoogle Scholar
  44. 44.
    Remijnse PL, van den Heuvel OA, Veltman DJ (2005) Neuroimaging in obsessive-compulsive disorder. Current Medical Imaging Reviews 1:331–351CrossRefGoogle Scholar
  45. 45.
    Remy P, Doder M, Lees A, Turjanski N, Brooks D (2005) Depression in Parkinson’s disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain 128:1314–1322PubMedCrossRefGoogle Scholar
  46. 46.
    Romito LM, Raja M, Daniele A, et al. (2002) Transient mania with hypersexuality after surgery for high frequency stimulation of the subthalamic nucleus in Parkinson’s disease. Mov Disord 17:1371–1374PubMedCrossRefGoogle Scholar
  47. 47.
    Saka E, Goodrich C, Harlan P, Madras BK, Graybiel AM (2004) Repetitive behaviors in monkeys are linked to specific striatal activation patterns. J Neurosci 24:7557–7565PubMedCrossRefGoogle Scholar
  48. 48.
    Sevincok L, Akoglu A, Akyol A (2007) Quetiapine in a case with Parkinson’s disease and pathological gambling. J Clin Psychopharmacol 27:107–108PubMedCrossRefGoogle Scholar
  49. 49.
    Shiba M, Bower JH, Maraganore DM, et al. (2000) Anxiety disorders and depressive disorders preceding Parkinson’s disease: a case-control study. Mov Disord 15:669–677PubMedCrossRefGoogle Scholar
  50. 50.
    Silveira-Moriyama L, Evans AH, Katzenschlager R, Lees AJ (2006) Punding and dyskinesias. Mov Disord 21:2214–2217PubMedCrossRefGoogle Scholar
  51. 51.
    Truong DD, Bhidayasiri R, Wolters E (2008) Management of non-motor symptoms in advanced Parkinson disease. J Neurol Sci 266:216–228PubMedCrossRefGoogle Scholar
  52. 52.
    Uitti RJ, Baba Y, Wszolek ZK, Putzke DJ (2005) Defining the Parkinson disease phenotype: initial symptoms and baseline characteristics in a clinical cohort. Parkinsonism Relat Disord 11:139–145PubMedCrossRefGoogle Scholar
  53. 53.
    van de Witte SV, Groenewegen HJ, Voorn P (2002) MK-801 alters the effects of priming with L-DOPA on dopamine D1 receptor-induced changes in neuropeptide mRNA levels in the rat striatal output neurons. Synapse 43:1–11PubMedCrossRefGoogle Scholar
  54. 54.
    van den Heuvel OA, Veltman DJ, Groenewegen HJ, et al. (2005) Disorder-specific neuroanatomical correlates of attentional bias in obsessive-compulsive disorder, panic disorder, and hypochondriasis. Arch General Psychiat 62:922–933CrossRefGoogle Scholar
  55. 55.
    van Dongen YC, Deniau JM, Pennartz CM, et al. (2005) Anatomical evidence for direct connections between the shell and core subregions of the rat nucleus accumbens. Neuroscience 136:1049–1071PubMedCrossRefGoogle Scholar
  56. 56.
    Voon V, Hassan K, Zurowski M, et al. (2006) Prospective prevalence of pathologic gambling and medication association in Parkinson disease. Neurology 66:1750–1752PubMedCrossRefGoogle Scholar
  57. 57.
    Voon V, Hassan K, Zurowski M, de Souza M, Thomsen T, Fox S, Lang AE, Miyasaki J (2006) Prevalence of repetitive and reward-seeking behaviors in Parkinson’s disease. Neurology 67:1254–1257PubMedCrossRefGoogle Scholar
  58. 58.
    Voon V, Potenza MN, Thompsen T (2007) Medication-related impulse control and repetitive behaviors in Parkinson’s disease. Curr Opin Neurol 20:484–492PubMedCrossRefGoogle Scholar
  59. 59.
    Voon V, Thompsen T, Miyasaki JM, et al. (2007) Factors associated with dopaminergic drug-related pathological gambling in Parkinson’s disease. Arch Neurol 64:212–216PubMedCrossRefGoogle Scholar
  60. 60.
    Weintraub D, Siderowf AD, Potenza MN, et al. (2006) Association of dopamine agonist use with impulse control disorders in Parkinson’s disease. Arch Neurol 63:969–973PubMedCrossRefGoogle Scholar
  61. 61.
    Wolters EC, Francot C, Bergmans P, Winogrodzka A, Booij J, Berendse HW, Stoof JC (2000) Preclinical (premotor) Parkinson’s disease. J Neurol 247:II103–II109PubMedGoogle Scholar
  62. 62.
    Wolters E, Braak H (2006) Parkinson’s disease: premotor clinico-pathological correlations. J Neural Transm Suppl 70:309–319PubMedCrossRefGoogle Scholar
  63. 63.
    Wolters ECh (2008) Variability in the clinical expression of Parkinson’s disease. J Neurol Sci 266:197–203PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Eric Ch. Wolters
    • 1
  • Ysbrand D. van der Werf
    • 2
    • 3
  • Odile A. van den Heuvel
    • 4
  1. 1.Dept. of NeurologyVU University Medical CenterAmsterdamThe Netherlands
  2. 2.Dept. of Clinical NeurophysiologyVU University Medical CenterAmsterdamThe Netherlands
  3. 3.Dept. Sleep and CognitionNetherlands Institute for Neuroscience an Institute of the Royal Netherlands Academy of Arts and SciencesAmsterdamThe Netherlands
  4. 4.Dept. of Psychiatry and Anatomy & NeurosciencesVU University Medical CenterAmsterdamThe Netherlands

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