Remy P, Doder M, Lees A, Turjanski N, Brooks D. Depression in Parkinson's disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain 128: 1314-1322

CNRS-CEA URA2210, Service Hospitalier Frédéric Joliot, CHU Henri Mondor et Faculté de Médecine Paris 12, France.
Brain (Impact Factor: 9.2). 07/2005; 128(Pt 6):1314-22. DOI: 10.1093/brain/awh445
Source: PubMed


The reason for the high frequency of depression and anxiety in Parkinson's disease is poorly understood. Degeneration of neurotransmitter systems other than dopamine might play a specific role in the occurrence of these affective disorders. We used [11C]RTI-32 PET, an in vivo marker of both dopamine and noradrenaline transporter binding, to localize differences between depressed and non-depressed patients. We studied eight and 12 Parkinson's disease patients with and without a history of depression matched for age, disease duration and doses of antiparkinsonian medication. The depressed Parkinson's disease cohort had lower [11C]RTI-32 binding than non-depressed Parkinson's disease cases in the locus coeruleus and in several regions of the limbic system including the anterior cingulate cortex, the thalamus, the amygdala and the ventral striatum. Exploratory analyses revealed that the severity of anxiety in the Parkinson's disease patients was inversely correlated with the [11C]RTI-32 binding in most of these regions and apathy was inversely correlated with [11C]RTI-32 binding in the ventral striatum. These results suggest that depression and anxiety in Parkinson's disease might be associated with a specific loss of dopamine and noradrenaline innervation in the limbic system.

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Available from: Philippe Remy, Apr 14, 2014
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    • "Except for suffering from the symptoms, patients are also greatly impacted emotionally. Decrease of dopamine in the limbic system plays a role in emotional stress and depression (Remy et al., 2005). Clinically, anxiety and depression were commonly found in PD patients. "
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    ABSTRACT: Complementary therapy with acupuncture for Parkinson's disease (PD) has been studied for quite a long time, but the effectiveness of the treatment still remains unclear. The aim of this study is to evaluate the integrated effects of acupuncture treatment in PD patients who received western medicine. In the short-term acupuncture treatment study, 20 patients received acupuncture therapy twice a week in acupoints DU 20, GB 20, LI 11, LI 10, LI 4, GB 31, ST 32, GB 34 and GB 38 along with western medicine for 18 weeks, and 20 controlled patients received western medicine only. In the long-term acupuncture treatment, 13 patients received acupuncture treatment twice a week for 36 weeks. The outcome parameters include Unified Parkinson's disease rating scale (UPDRS), Beck Anxiety Inventory (BAI), Beck Depression Inventory-Version 2 (BDI-II), and WHO quality of life (WHOQOL). In the short-term clinical trial, a higher percentage of patients in the acupuncture group had score improvement in UPDRS total scores (55% vs. 15%, p = 0.019), sub-score of mind, behavior and mood (85% vs. 25%, p < 0.001), activity of daily living (65% vs. 15%, p = 0.003), mobility (40% vs. 15%, p = 0.155) and complication of treatment (75% vs. 15%, p < 0.001), BDI-II score (85% vs. 35%, p = 0.003), and WHOQOL score (65% vs. 15%, p = 0.003) when compared to control group at the end of the 18 weeks' follow up. After 36 weeks of long-term acupuncture treatment, the mean UPDRS total scores and sub-score of mentation, behavior and mood, sub-score of complications of therapy and BDI-II score decreased significantly when compared to the pretreatment baseline. In conclusion, acupuncture treatment had integrated effects in reducing symptoms and signs of mind, behavior, mood, complications of therapy and depression in PD patients who received Western medicine.
    The American Journal of Chinese Medicine 05/2015; 43(3):407-23. DOI:10.1142/S0192415X15500263 · 2.76 Impact Factor
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    • "The pathophysiology of such disorders has not yet been completely understood but includes lesions of the dopaminergic, serotoninergic, and noradrenergic systems involved in Parkinson's disease (Hirsch et al., 2003; Kish et al., 2008). However, a change in the mesocorticolimbic dopaminergic system could play a role in the behavioral disorders of PD (Remy et al., 2005). Indeed, in addition to the lesion of the dopaminergic nigrostriatal system, other dopaminergic systems are also damaged in PD, namely those originating in the ventral tegmental area (VTA) that project to the limbic system , which is involved in the reward circuit (mesolimbic system), and also to the prefrontal cortex, which is involved in personality traits (mesocortical system) (Tzschentke, 2001; Haber and Knutson, 2010). "
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    ABSTRACT: Parkinsonian patients experience not only the physical discomfort of motor disorders but also the considerable psychological distress caused by cognitive deficits and behavioral disorders. These two factors can result in a disruption of social relationships during the symptomatic and even the presymptomatic motor states of the disease. However, it remains difficult, if not impossible, to evaluate social relationships in presymptomatic patients. The present study focused on the evaluation of social relationships within a group of female long-tailed macaques during presymptomatic and symptomatic motor states induced by Chronic Low-Dose (CLD) and then Chronic High-Dose (CHD) systemic administration of 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP). Dopaminergic denervation within basal ganglia and cortical areas was evaluated using Positron Emission Tomography (PET) scans with 18 F-DOPA (6-[18F]-fluoro-L-3,4-dihydroxyphenylalanine) radiotracer. Interestingly, social behavioral changes could be identified in the presymptomatic motor state before any motor and/or cognitive impairment occurred. Stronger effects were observed in subordinate animals compared to dominant animals. From baseline state to CLD-presymptomatic motor state, the frequency of emitted affiliative and aggressive behaviors increased. From CLD-presymptomatic to CHD-presymptomatic motor states, the frequency of the three categories of social behaviors (aggressive, submissive and affiliative) decreased. At this time, quantitative data analysis in PET scans highlighted a dopaminergic denervation in the insula and the posterior caudate nucleus. Finally, the frequency of the three categories of social behaviors decreased during the stable-symptomatic motor state compared to baseline and presymptomatic motor states; this was also associated with motor and cognitive disorders and a dopaminergic denervation in all the evaluated cortical and subcortical structures.
    Frontiers in Behavioral Neuroscience 02/2015; 9. DOI:10.3389/fnbeh.2015.00042 · 3.27 Impact Factor
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    • "Overall these studies suggest that apathy may result at least in part from disruption/dysfunction of " cognitive " dopaminergic caudate-frontal cortex circuits. In more advanced depressed PD patients reduced 11C-RTI-32 binding in ventral striatum was inversely correlated with the degree of apathy [22]. It is noteworthy , however, that 11C-RTI-32 is a marker of both dopamine and noradrenaline transporters and thus it does not provide information on the specific contribution of DA loss in the occurrence of apathy. "
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    ABSTRACT: Apathy is a neuropsychiatric symptom in Parkinson's Disease (PD) which has a negative impact on quality of life and might be related in part to damage of presynaptic dopaminergic system. Little is known about relationship between striatal dopamine levels and apathy in PD patients without dementia and/or depression. The aim of the present study was to investigate the relationship between "pure apathy" and striatal dopamine uptake in untreated, drug-naïve PD patients without clinically significant dementia and/or depression. Fourteen PD patients with pure apathy and 14 PD patients without apathy, matched for age, side of motor symptoms at onset, motor disability and disease duration, underwent both neuropsychological and behavioral examination including self-rated version of the Apathy Evaluation Scale (AES-S). All patients underwent 123 I-FP-CIT (DaT-SCAN) SPECT to assess dopamine transporter (DAT) striatal uptake. PD patients with apathy showed lower DAT levels in the striatum than non-apathetic patients. After Bonferroni correction the difference between groups was significant in the right caudate. Apathy is associated with reduced striatal dopamine transporter levels, independent of motor disability and depression in non-demented PD patients. These findings suggest that dysfunction of dopaminergic innervation in the striatum and particularly in the right caudate may contribute to development of apathy in early PD. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Parkinsonism & Related Disorders 02/2015; 21(5). DOI:10.1016/j.parkreldis.2015.02.015 · 3.97 Impact Factor
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