Up to 20% of patients with Parkinson's disease (PD) develop impulse control behaviours (ICBs) on dopaminergic therapy, particularly on dopamine receptor agonists. Impulsive behaviour can include pathological gambling, shopping, hypersexuality, binge eating and punding, all of which can have a debilitating impact on patients and their families. Treatment often consists of reducing the dose of dopamine agonists, significantly limiting optimal therapy of motor symptoms in PD.
One critical - and controversial - issue is why some PD patients develop ICBs. A recent paper by Hammes et al. (2018) provides important new insights into the underlying mechanisms. The investigators used fluorodopa PET (F-DOPA-PET) to measure dopamine synthesis capacity, resting state fMRI to measure functional connectivity and structural MRI in a large sample of PD patients. A key result was that there was a significant negative correlation between dopamine synthesis capacity in the nucelus accumbens (NAc) and the severity of ICBs. Moreover, PD patients with more severe ICBs had weaker functional connectivity between the NAc and the rostral anterior cingulate cortex (ACC)
The findings suggest that the fundamental disorder that predisposes to ICBs might lie in dysfunction of the mesocorticolimbic pathway - the dopaminergic projection from the ventral tegmental area (VTA) to the NAc and the connections of the latter to the medial prefrontal cortex, including the ACC. Reduced dopaminergic projections from VTA to NAc together with weaker onward connections to the ACC may place PD patients at higher risk of developing ICBs.
1. Impulse control behaviours are common and impact severely on the treatment of Parkinson's disease patients.
2. A new study suggests a key mechanism might lie in a dysfunctional mesocorticolimbic system.
3. Specifically there may be lower dopamine synthesis in the nucleus accumbens due to reduced projections from the ventral tegmental area plus decreased functional connectivity of the accumbens with the anterior cingulate cortex in Parkinson's patients with impulse control behaviours.
references:
[1] Weintraub D, Claassen DO. <link www.ncbi.nlm.nih.gov/pubmed/28802938 - external-link-new-window "Opens external link in new window">Impulse Control and Related Disorders in Parkinson's Disease.</link> Int. Rev. Neurobiol., 2017;133:679-717. Pubmed link.
[2] Voon V, Napier TC, Frank MJ, Sgambato-Faure V, Grace AA, Rodriguez-Oroz M, et al. <link www.ncbi.nlm.nih.gov/pubmed/28229895 - external-link-new-window "Opens external link in new window">Impulse control disorders and levodopa-induced dyskinesias in Parkinson's disease: an update.</link> Lancet Neurol 2017;16:238-50. Pubmed link.
[3] Hammes J, Theis H, Giehl K, Hoenig MC, Greuel A, Tittgemeyer M, et al. <link academic.oup.com/brain/advance-article-abstract/doi/10.1093/brain/awz007/5310124 - external-link-new-window "Opens external link in new window">Dopamine metabolism of the nucleus accumbens and fronto-striatal connectivity modulate impulse control.</link> Brain 2019; Epub ahead of print. Oxford University Press link.