J Neurol (2008) 255 [Suppl 5]:51–59 DOI 10.1007/s00415-008-5010-5 Journal of Neurology-S (JON-Supplement) Ms. No. JON 5010 Steinkopff Verlag, Heidelberg/ottomedien, Darmstadt 1. run Provisional page numbers 51–59 Date 00.00.0000 JON 5010 Eric C. Wolters Ysbrand D. van der Werf Odette A. van den Heuvel Parkinson’s disease-related disorders in the impulsive-compulsive spectrum ■ Abstract In Parkinson’s disease (PD), there is increasing evidence for disorders in the impulsive- compulsive spectrum, related to the disease itself, to the pharmacologi- cal management of this disease or to both. These disorders comprise dopamine deficiency syndrome (with immediate reward seeking behaviour), dopamine dependency syndrome (with addictive behav- iour), dopamine dysregulation syn- drome (with both addictive behav- iour and stereotyped behaviour) and impulse control disorders (such as pathological gambling, compulsive shopping, binge eating and hypersexuality). These disor- ders are especially seen in PD pa- tients with young age of onset, higher doses of antiparkinsonian drugs, pre-existent or current depression, pre-existing recrea- tional drug or alcohol use, and high novelty seeking personality traits. Dopamine is not only impli- cated in voluntary movement con- trol but also plays a significant role in the brain’s reward system and the modulation of behaviours. Therefore, most if not all drug- naïve PD patients will suffer dys- phoria, leading to mild immediate reward seeking behaviour as a con- sequence of the striatal dopamin- ergic denervation. In some of these patients, during treatment, this may even lead to the intake of in- creasing quantities of levodopa, above those required to adequately treat motor parkinsonism, with all characteristics of a dopamine dependence syndrome. These pa- tients may develop plastic changes in the striatal matrix leading to hyperkinesia, caused by extracellu- lar striatal dopaminergic fluctua- tions due to pulsatile dopamine replacement therapy. As soon as these changes are also seen in the striatal striosomes, in the frame- work 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 over- activity) so far has not been described in PD patients. Treatment of impulse control disorders is related to the underly- ing pathology. In the case of an intrinsic dopamine deficiency syn- drome, treatment with dopamine replacement therapy, especially levodopa, will help. In the multi- factorial (intrinsic and extrinsic) dopamine dependency and dysreg- ulation syndromes, addictive be- haviour might best be helped by psychosocial strategies, and pund- ing by continuous dopaminergic receptor stimulation (or amanta- dine), hypothesized to reduce the plastic changes-induced hypersen- sitization. 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 E. C. Wolters (Y) Dept. of Neurology VU University Medical Center P. O. Box 7057 1007 MB Amsterdam, The Netherlands E-Mail: E.Wolters@vumc.nl Y. D. van der Werf Dept. of Medical Psychology VU University Medical Center P. O. Box 7057 1007 MB Amsterdam, The Netherlands and Dept. Sleep and Cognition Netherlands Institute for Neuroscience an Institute of the Royal Netherlands Academy of Arts and Sciences Amsterdam, The Netherlands O. A. van den Heuvel Dept. of Psychiatry and Anatomy & Neurosciences VU University Medical Center P. O. Box 7057 1007 MB Amsterdam, The Netherlands