title: Apathy and Impulse Control Disorders: Yin & Yang of Dopamine Dependent Behaviors.
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.
authors: 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.
authors: María
authors: M
authors: Sierra
authors: INSERM, Unit 836, Grenoble Institut des Neurosciences, Grenoble, France.
authors: Sébastien
authors: S
authors: Carnicella
authors: 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.
authors: Antonio P
authors: AP
authors: Strafella
authors: 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.
authors: Amélie
authors: A
authors: Bichon
authors: 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.
authors: Eugénie
authors: E
authors: Lhommée
authors: 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.
authors: Anna
authors: A
authors: Castrioto
authors: Department of Neurosurgery CHU de Grenoble, Joseph Fourier University, Grenoble, France and INSERM, Unité 836, Grenoble Institut des Neurosciences, Grenoble, France.
authors: Stephan
authors: S
authors: Chabardes
authors: 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.
authors: Stéphane
authors: S
authors: Thobois
authors: 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.
authors: Paul
authors: P
authors: Krack
mesh_terms: D000818:Animals; D057565:Apathy / Q000502:physiology*; D001921:Brain / Q000503:physiopathology*; D046690:Deep Brain Stimulation; D004195:Disease Models, Animal; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000150:complications / Q000503:physiopathology*; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000008:administration & dosage; D006801:Humans; D010300:Parkinson Disease / Q000150:complications / Q000503:physiopathology* / Q000523:psychology* / Q000628:therapy; D011954:Receptors, Dopamine / Q000502:physiology
chemical_list: D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D004298:Dopamine
keywords: Apathy; Parkinson’s disease; dopamine dysregulation syndrome; impulse control disorders; punding