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      Stress and Mindfulness in Parkinson's Disease: Clinical Effects and Potential Underlying Mechanisms

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          ABSTRACT

          Patients with Parkinson's disease (PD) are very vulnerable to the negative effects of psychological distress: neuropsychiatric symptoms, such as anxiety and depression, are highly prevalent in PD; motor symptoms (such as tremor) typically worsen in stressful situations; and dopaminergic medication is less effective. Furthermore, animal studies of PD suggest that chronic stress may accelerate disease progression. Adequate self‐management strategies are therefore essential to reduce the detrimental effects of chronic stress on PD. Mindfulness‐based interventions encourage individuals to independently self‐manage and adapt to the challenges created by their condition. In PD, emerging clinical evidence suggests that mindfulness‐based interventions may reduce psychological distress and improve clinical symptoms, but insight into the underlying mechanisms is lacking. In this viewpoint, we provide a systematic overview of existing mindfulness trials in PD. Furthermore, we discuss the cerebral mechanisms involved in acute and chronic stress, and the impact of mindfulness‐based interventions on these networks. In addition, we delineate a hypothetical mechanistic framework of how chronic stress may increase the susceptibility for neuropsychiatric symptoms in PD and may potentially even influence disease progression. We end with offering recommendations for future research. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

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          The neuroscience of mindfulness meditation.

          Research over the past two decades broadly supports the claim that mindfulness meditation - practiced widely for the reduction of stress and promotion of health - exerts beneficial effects on physical and mental health, and cognitive performance. Recent neuroimaging studies have begun to uncover the brain areas and networks that mediate these positive effects. However, the underlying neural mechanisms remain unclear, and it is apparent that more methodologically rigorous studies are required if we are to gain a full understanding of the neuronal and molecular bases of the changes in the brain that accompany mindfulness meditation.
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            The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis.

            There is considerable, although not entirely consistent, evidence that the hippocampus inhibits most aspects of HPA activity, including basal (circadian nadir) and circadian peak secretion as well as the onset and termination of responses to stress. Although much of the evidence for these effects rests only on the measurement of corticosteroids, recent lesion and implant studies indicate that the hippocampus regulates adrenocortical activity at the hypothalamic level, via the expression and secretion of ACTH secretagogues. Such inhibition results largely from the mediation of corticosteroid feedback, although more work is required to determine whether the hippocampus supplies a tonic inhibitory input in the absence of corticosteroids. It must be noted that the hippocampus is not the only feedback site in the adrenocortical system, since removal of its input only reduces, but does not abolish, the efficacy of corticosteroid inhibition, and since other elements of the axis appear eventually to compensate for deficits in feedback regulation. The importance of other feedback sites is further suggested not only by the presence of corticosteroid receptors in other parts of the brain and pituitary, but also by the improved prediction of CRF levels by combined hypothalamic and hippocampal receptor occupancy. The likelihood of feedback mediated by nonhippocampal sites underscores the need for future work to characterize hippocampal influence on HPA activity in the absence of changes in corticosteroid secretion. However, despite the fact that the hippocampus is not the only feedback site, it is distinguished from most potential feedback sites, including the hypothalamus and pituitary, by its high content of both type I and II corticosteroid receptors. The hippocampus is therefore capable of mediating inhibition over a wide range of steroid levels. The low end of this range is represented by corticosteroid inhibition of basal (circadian nadir) HPA activity. The apparent type I receptor specificity of this inhibition and the elevation of trough corticosteroid levels after hippocampal damage support a role for hippocampal type I receptors in regulating basal HPA activity. It is possible that basal activity is controlled in part through hippocampal inhibition of vasopressin, since the inhibition of portal blood vasopressin correlates with lower levels of hippocampal receptor occupancy, and the expression of vasopressin by some CRF neurons is sensitive to very low corticosteroid levels. At the high end of the physiological range, stress-induced or circadian peak corticosteroid secretion correlates strongly with occupancy of the lower affinity hippocampal type II receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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              The human stress response

              The human stress response has evolved to maintain homeostasis under conditions of real or perceived stress. This objective is achieved through autoregulatory neural and hormonal systems in close association with central and peripheral clocks. The hypothalamic-pituitary-adrenal axis is a key regulatory pathway in the maintenance of these homeostatic processes. The end product of this pathway - cortisol - is secreted in a pulsatile pattern, with changes in pulse amplitude creating a circadian pattern. During acute stress, cortisol levels rise and pulsatility is maintained. Although the initial rise in cortisol follows a large surge in adrenocorticotropic hormone levels, if long-term inflammatory stress occurs, adrenocorticotropic hormone levels return to near basal levels while cortisol levels remain raised as a result of increased adrenal sensitivity. In chronic stress, hypothalamic activation of the pituitary changes from corticotropin-releasing hormone-dominant to arginine vasopressin-dominant, and cortisol levels remain raised due at least in part to decreased cortisol metabolism. Acute elevations in cortisol levels are beneficial to promoting survival of the fittest as part of the fight-or-flight response. However, chronic exposure to stress results in reversal of the beneficial effects, with long-term cortisol exposure becoming maladaptive, which can lead to a broad range of problems including the metabolic syndrome, obesity, cancer, mental health disorders, cardiovascular disease and increased susceptibility to infections. Neuroimmunoendocrine modulation in disease states and glucocorticoid-based therapeutics are also discussed.
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                Author and article information

                Contributors
                a.vanderheide@donders.ru.nl
                Journal
                Mov Disord
                Mov Disord
                10.1002/(ISSN)1531-8257
                MDS
                Movement Disorders
                John Wiley & Sons, Inc. (Hoboken, USA )
                0885-3185
                1531-8257
                23 October 2020
                January 2021
                : 36
                : 1 ( doiID: 10.1002/mds.v36.1 )
                : 64-70
                Affiliations
                [ 1 ] Department of Neurology, Centre of Expertise for Parkinson & Movement Disorders Radboud University Medical Centre Nijmegen the Netherlands
                [ 2 ] Donders Institute for Brain, Cognition, and Behavior, Centre for Cognitive Neuroimaging Radboud University Nijmegen Nijmegen the Netherlands
                [ 3 ] Radboud Institute for Health Sciences Radboud University Medical Centre Nijmegen the Netherlands
                [ 4 ] Radboud University Medical Centre Department of Psychiatry, Centre for Mindfulness Nijmegen the Netherlands
                Author notes
                [*] [* ] Correspondence to: Ms. Anouk van der Heide, Donders Institute for Brain, Cognition and Behaviour, PO Box 9101, 6500 HB Nijmegen, the Netherlands; E‐mail: a.vanderheide@ 123456donders.ru.nl

                Author information
                https://orcid.org/0000-0003-4035-6573
                Article
                MDS28345
                10.1002/mds.28345
                7894549
                33094858
                d5e65fca-9163-49f0-9595-41362a07efdb
                © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 June 2020
                : 09 September 2020
                : 03 October 2020
                Page count
                Figures: 2, Tables: 1, Pages: 7, Words: 5419
                Funding
                Funded by: Michael J. Fox Foundation for Parkinson's Research , open-funder-registry 10.13039/100000864;
                Award ID: #16048
                Funded by: Nederlandse Organisatie voor Wetenschappelijk Onderzoek , open-funder-registry 10.13039/501100003246;
                Award ID: VENI grant #91617077
                Categories
                Viewpoint
                Regular Issue Articles
                Viewpoints
                Custom metadata
                2.0
                January 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.7 mode:remove_FC converted:19.02.2021

                Medicine
                parkinson's disease,mindfulness,psychological stress,anxiety,depression,quality of life
                Medicine
                parkinson's disease, mindfulness, psychological stress, anxiety, depression, quality of life

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