Anhedonia, a core symptom of depression, correlates with motor alterations in major depressive disorder and has been assumed to be frequent in depressed patients with Parkinson's disease (PD). In the present study, the authors assessed for the first time frequency of anhedonia in patients with idiopathic Parkinson's disease (N = 657) and the relationship of anhedonia and parkinsonian motor deficits during treatment with pramipexole. Mild depression was present in 47% of the patients and moderate to severe depression in 22%. Anhedonic individuals included 45.7% of all patients and 79.7% of depressed Parkinson's disease patients. Anhedonic Parkinson's disease patients had greater motor deficits, restrictions in activities of daily living, and depression compared to nonanhedonic patients. Frequency of anhedonia and depression was significantly reduced during treatment with pramipexole. Future studies should further investigate antianhedonic efficacy of dopamine agonists including pramipexole in depressed patients with Parkinson's disease.
"Dopamine replacement therapies have revolutionized outcomes of motor function and pre-clinical research is currently largely focused on characterizing and targeting effects that go beyond the dopamine system, including a panoply of motor and non-motor symptoms with no specific symptom or domain obviously dominating the patient experience. Better management of many non-motor symptoms awaits success of these pre-clinical efforts   . "
[Show abstract][Hide abstract] ABSTRACT: Parkinson's Disease (PD) involves well known motor symptoms such as tremor, rigidity, bradykinesia, and altered gait but there are also non-locomotory motor symptoms (e.g., changes in handwriting and speech) and even non-motor symptoms (e.g., disrupted sleep, depression) that can be measured, monitored, and possibly better managed through activity based monitoring technologies. This will enhance quality of life (QoL) in PD through improved self-monitoring, and also provide information which could be shared with a health care provider to help better manage treatment. Until recently, non-motor symptoms ("soft signs") had been generally overlooked in clinical management yet these are of primary importance to patients and their QoL. Day-to-day variability of the condition, the high variability in symptoms between patients, and the isolated snapshots of a patient in periodic clinic visits makes better monitoring essential to the proper management of PD. Continuously monitored patterns of activity, social interactions, and daily activities could provide a rich source of information on status changes, guiding self correction and clinical management. The same tools can be useful in earlier detection of PD and will improve clinical studies. Remote medical communications in the form of telemedicine, sophisticated tracking of medication use, and assistive technologies that directly compensate for disease related challenges are examples of other near term technology solutions to PD problems. Ultimately, a sensor technology is no good if it is not used. The Parkinson's community is a sophisticated early adopter of useful technologies and a group for which engineers can provide near term gratifying benefits.
"An illustration of this theory is shown in the case of pramipexole, a dopamine D 3 /D 2 receptor agonist used in the treatment of Parkinson symptoms. Pramipexole reduces depressive symptoms in Parkinson's patients suffering from depression (Lemke et al., 2005; 2006). A low dose of pramipexole (0.3 mg/kg i.p.) reduced the OBX-induced hyperactivity after 7 and 14 days of pretreatment. "
"More recently, several studies have demonstrated that the dopaminergic system is implicated in the efficacy of antidepressant drug action (Bymaster et al., 2003; Pania and Gessab, 2002). The involvement of dopamine in depression is thought to be dependent on dopaminergic reward mechanisms in the limbic system (Lemke et al., 2005). Indeed, the hypofunction of the mesolimbic dopaminergic pathway is responsible for anhedonia , one of the major symptoms of depression, which is scarcely affected by SSRI treatment (Kulkarni and Dhir, 2009; Willner, 1983). "
[Show abstract][Hide abstract] ABSTRACT: A substantial proportion of depressed patients do not respond to current antidepressant drug therapies. So far, antidepressant drugs have been developed based on the "monoaminergic hypothesis" of depression, which considers a synaptic deficiency in 5-hydroxytryptamine (5-HT; serotonin) or noradrenaline as main cause. More recently, the dopaminergic system has been implicated in the efficacy of some antidepressants, such as desipramine, amineptine, nomifensine. Dysfunction of dopaminergic neurotransmission within the mesolimbic system may contribute to anhedonia, loss of motivation and psychomotor retardation in severe depressive disorders. Dopamine D3 receptor subtype is located both pre- and postsynaptically in brain areas regulating motivation and reward-related behavior and has been implicated in depression-like behaviors. Activity of mesolimbic dopamine neurons in the reward circuit is a key determinant of behavioral susceptibility/resilience to chronic stress, which plays a central role in the pathogenesis of depression. Dopamine D3 receptor expression and function are both down-regulated in stress and depression, and these changes are reversed by antidepressant treatments, suggesting that enhanced dopaminergic neurotransmission mediated by dopamine D3 receptor participates in adaptive changes related to antidepressant activity. Of note, brain derived neurotrophic factor (BDNF) controls the expression of the dopamine D3 receptor in some brain areas and BDNF induction by antidepressant treatments is related to their behavioral activity. A number of experimental drugs in pre-clinical or clinical development, including aripiprazole and cariprazine, may act as antidepressants because of their partial agonist activity at dopamine D3 receptors. These preclinical and clinical data are discussed in the present review.
European journal of pharmacology 07/2013; 719(1-3). DOI:10.1016/j.ejphar.2013.07.022 · 2.53 Impact Factor
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