Apathy and Impulse Control Disorders: Yin & Yang of Dopamine Dependent Behaviors

Issue title: Special Section: Selected Papers from the 10th International congress on Non-Motor Dysfunctions in Parkinson’s Disease and Related Disorders, Nice, France, December 4–7, 2014

Article type: Review Article

Authors: Sierra, María^a | Carnicella, Sébastien^b | Strafella, Antonio P.^c | Bichon, Amélie^d | Lhommée, Eugénie^d | Castrioto, Anna^d | Chabardes, Stephan^e | Thobois, Stéphane^f | Krack, Paul^{d; *}

Affiliations: [a] Service of Neurology, University Hospital “Marqués de Valdecilla (IFIMAV)”, University of Cantabria and “Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED)”, Santander, Spain | [b] INSERM, Unit 836, Grenoble Institut des Neurosciences, Grenoble, France | [c] Morton and Gloria Shulman Movement Disorder Unit - E.J. Safra Parkinson Disease Program, Toronto Western Hospital and Research Institute, UHN & Research Imaging Centre, Campbell Family Mental Health Research Institute, CAMH, University of Toronto, Ontario, Canada | [d] Movement Disorder Unit, Department of Psychiatry and Neurology, CHU de Grenoble, Joseph Fourier University, Grenoble Universités, France; and INSERM, Unit 836, Grenoble Institut des Neurosciences, Grenoble, France | [e] Department of Neurosurgery CHU de Grenoble, Joseph Fourier University, Grenoble, France and INSERM, Unité 836, Grenoble Institut des Neurosciences, Grenoble, France | [f] Université de Lyon, F-69622, Lyon, France; Université Lyon 1, Villeurbanne, France; CNRS, UMR5229, Centre de Neuroscience Cognitive, Bron, France; Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, France

Correspondence: [*] Correspondence to: Paul Krack, Movement Disorder Unit, Department of Psychiatry and Neurology, CHU de Grenoble, Joseph Fourier University, Grenoble Universités, France; and INSERM, Unit 836, Grenoble Institut des Neurosciences, Grenoble, France. Tel.: +33 4 76 76 94 52; Fax: +33 4 76 76 56 31; [email protected]

Abstract: Neuropsychiatric symptoms are common non-motor symptoms in Parkinson’s disease (PD). Apathy and impulse control disorders (ICD) are two opposite motivational expressions of a continuous behavioural spectrum involving hypo- and hyperdopaminergia. Both syndromes share pathological (decreased vs increased) dopamine receptor stimulation states. Apathy belongs to the spectrum of hypodopaminergic symptoms together with anhedonia, anxiety and depression. Apathy is a key symptom of PD which worsens with disease progression. Animal models, imaging and pharmacological studies concur in pointing out dopaminergic denervation in the aetiology of parkinsonian apathy with a cardinal role of decreased tonic D2/D3 receptor stimulation. ICDs are part of the hyperdopaminergic behavioural spectrum, which also includes punding, and dopamine dysregulation syndrome (DDS), which are all related to non-physiological dopaminergic stimulation induced by antiparkinsonian drugs. According to clinical data tonic D2/D3 receptor stimulation can be sufficient to induce ICDs. Clinical observations in drug addiction and PD as well as data from studies in dopamine depleted rodents provide hints allowing to argue that both pulsatile D1 and D2 receptor stimulation and the severity of dopaminergic denervation are risk factors to develop punding behavior and DDS. Imaging studies have shown that the brain structures involved in drug addiction are also involved in hyperdopaminergic behaviours with increase of bottom-up appetitive drive and decrease in prefrontal top down behavioural control.

Keywords: Apathy, Parkinson’s disease, impulse control disorders, dopamine dysregulation syndrome, punding

DOI: 10.3233/JPD-150535

Journal: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 625-636, 2015