scholarly journals Disrupted reward processing in Parkinson’s disease and its relationship with dopamine state and neuropsychiatric syndromes: a systematic review and meta-analysis

2021 ◽  
pp. jnnp-2021-327762
Author(s):  
Harry Costello ◽  
Alex J Berry ◽  
Suzanne Reeves ◽  
Rimona S Weil ◽  
Eileen M Joyce ◽  
...  

BackgroundNeuropsychiatric symptoms are common in Parkinson’s disease (PD) and predict poorer outcomes. Reward processing dysfunction is a candidate mechanism for the development of psychiatric symptoms including depression and impulse control disorders (ICDs). We aimed to determine whether reward processing is impaired in PD and its relationship with neuropsychiatric syndromes and dopamine replacement therapy.MethodsThe Ovid MEDLINE/PubMed, Embase and PsycInfo databases were searched for articles published up to 5 November 2020. Studies reporting reward processing task performance by patients with PD and healthy controls were included. Summary statistics comparing reward processing between groups were converted to standardised mean difference (SMD) scores and meta-analysed using a random effects model.ResultsWe identified 55 studies containing 2578 participants (1638 PD and 940 healthy controls). Studies assessing three subcomponent categories of reward processing tasks were included: option valuation (n=12), reinforcement learning (n=37) and reward response vigour (n=6). Across all studies, patients with PD on medication exhibited a small-to-medium impairment versus healthy controls (SMD=0.34; 95% CI 0.14 to 0.53), with greater impairments observed off dopaminergic medication in within-subjects designs (SMD=0.43, 95% CI 0.29 to 0.57). Within-subjects subcomponent analysis revealed impaired processing off medication on option valuation (SMD=0.57, 95% CI 0.39 to 0.75) and reward response vigour (SMD=0.36, 95% CI 0.13 to 0.59) tasks. However, the opposite applied for reinforcement learning, which relative to healthy controls was impaired on-medication (SMD=0.45, 95% CI 0.25 to 0.65) but not off-medication (SMD=0.28, 95% CI −0.03 to 0.59). ICD was the only neuropsychiatric syndrome with sufficient studies (n=13) for meta-analysis, but no significant impairment was identified compared tonon-ICD patients (SMD=−0.02, 95% CI −0.43 to 0.39).ConclusionReward processing disruption in PD differs according to subcomponent and dopamine medication state, and warrants further study as a potential treatment target and mechanism underlying associated neuropsychiatric syndromes.

2021 ◽  
Author(s):  
Harry Costello ◽  
Alex Berry ◽  
Suzanne Reeves ◽  
Rimona S. Weil ◽  
Eileen Joyce ◽  
...  

Background: Neuropsychiatric symptoms are common in Parkinsons disease (PD) and predict poorer outcomes. Reward processing dysfunction is a candidate mechanism for the development of psychiatric symptoms including depression and impulse control disorders (ICD). We aimed to determine whether reward processing is impaired in PD and its relationship with neuropsychiatric syndromes and dopamine replacement therapy. Methods: The Ovid MEDLINE/PubMed, Embase and PsycInfo databases were searched for articles published up to November 5th, 2020. Studies reporting reward processing task performance by PD patients and healthy controls were included. Summary statistics comparing reward processing between groups were converted to standardized mean difference (SMD) scores and meta-analysed using a random effects model. Results: We identified 55 studies containing 2578 participants (1,638 PD and 940 healthy controls). Studies assessing three subcomponent categories of reward processing tasks were included: Option Valuation (n=12), Reinforcement Learning (n=37) and Reward Response Vigour (n=6). Across all studies, PD patients on medication exhibited a small-to-medium impairment versus healthy controls (SMD=0.34; 95%CI 0.14-0.53), with greater impairments observed off dopaminergic medication in within-subjects designs (SMD=0.43, 95%CI 0.29-0.57). Within-subjects subcomponent analysis revealed impaired processing off medication on Option Valuation (SMD=0.57, 95%CI 0.39-0.75) and Reward Response Vigour (SMD=0.36, 95%CI 0.13-0.59) tasks. However, the opposite applied for Reinforcement Learning, which relative to healthy controls was impaired on-medication (SMD=0.45, 95%CI 0.25-0.65) but not off-medication (SMD=0.28, 95%CI -0.03-0.59). ICD was the only neuropsychiatric syndrome with sufficient studies (n=13) for meta-analysis, but no significant impairment was identified compared to non-ICD patients (SMD=-0.02, 95%CI -0.43-0.39). Conclusion: Reward processing disruption in PD differs according to subcomponent and dopamine medication state and warrants further study as a potential treatment target and mechanism underlying associated neuropsychiatric syndromes.


2021 ◽  
Vol 34 (4) ◽  
pp. 310-320 ◽  
Author(s):  
Sneha R. Lopes ◽  
Sunna Khan ◽  
Suma Chand

Neuropsychiatric symptoms occur frequently in Parkinson’s disease (PD) patients. Pharmacological treatment of the psychiatric symptoms has been found to be inadequate. Cognitive behavior therapy (CBT) is an evidence based form of psychotherapy that is effective in treating a number of psychiatric disorders. In this article we examine the evidence of CBT in treating common psychiatric symptoms seen in PD patients, namely depression, anxiety, insomnia and impulse control behaviors. Most of the studies adapted CBT to address PD related concerns. Caregivers were frequently part of the CBT programs. Among the studies reviewed, randomized controlled trials showed significant effects in treating depression with CBT in PD patients. Studies have also provided preliminary data for effects of CBT on anxiety, impulse-control behaviors and insomnia. There is a need for more well designed studies with sufficient power for CBT to be established as a useful non-pharmacological treatment for psychiatric symptoms in PD.


2020 ◽  
Vol 8 (11) ◽  
pp. 1661
Author(s):  
Caroline Xie ◽  
Asheeta A. Prasad

Parkinson’s disease (PD) is a neurological disorder with motor dysfunction and a number of psychiatric symptoms. Symptoms such as anxiety and cognitive deficits emerge prior to motor symptoms and persist over time. There are limited treatments targeting PD psychiatric symptoms. Emerging studies reveal that the gut microbe is altered in PD patients. Here we assessed the effect of a probiotic treatment in a rat model of PD. We used the neurotoxin (6-hydroxydopamine, 6-OHDA) in a preclinical PD model to examine the impact of a probiotic treatment (Lacticaseibacillus rhamnosus HA-114) on anxiety and memory. Rats underwent either sham surgery or received 6-OHDA bilaterally into the striatum. Three weeks post-surgery, rats were divided into three experimental groups: a sham group that received probiotics, a 6-OHDA group that received probiotics, and the third group of 6-OHDA received the placebo formula. All rats had access to either placebo or probiotics formula for 6 weeks. All groups were assessed for anxiety-like behaviour using the elevated plus maze. Cognition was assessed for both non-hippocampal and hippocampal dependent tasks using the novel object recognition and novel place recognition. We report that the 6-OHDA lesion induced anxiety-like behaviour and deficits in hippocampal dependent cognition. Interestingly, the probiotics treatment had no impact on anxiety-like behaviour but selectively improved hippocampal dependent cognition deficits. Together, the results presented here highlight the utility of animal models in examining the neuropsychiatric symptoms of PD and the potential of probiotics as adjunctive treatment for non-motor symptoms of PD.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
John P Grogan ◽  
Demitra Tsivos ◽  
Laura Smith ◽  
Brogan E Knight ◽  
Rafal Bogacz ◽  
...  

Emerging evidence suggests that dopamine may modulate learning and memory with important implications for understanding the neurobiology of memory and future therapeutic targeting. An influential hypothesis posits that dopamine biases reinforcement learning. More recent data also suggest an influence during both consolidation and retrieval. Eighteen Parkinson’s disease patients learned through feedback ON or OFF medication, with memory tested 24 hr later ON or OFF medication (4 conditions, within-subjects design with matched healthy control group). Patients OFF medication during learning decreased in memory accuracy over the following 24 hr. In contrast to previous studies, however, dopaminergic medication during learning and testing did not affect expression of positive or negative reinforcement. Two further experiments were run without the 24 hr delay, but they too failed to reproduce effects of dopaminergic medication on reinforcement learning. While supportive of a dopaminergic role in consolidation, this study failed to replicate previous findings on reinforcement learning.


2021 ◽  
Vol 12 ◽  
Author(s):  
Junqiang Yan ◽  
Hongxia Ma ◽  
Anran Liu ◽  
Jiarui Huang ◽  
Jiannan Wu ◽  
...  

Objective: The effects of rotigotine transdermal patch (RTG) on the neuropsychiatric symptoms of Parkinson's disease (PD) outcomes remain controversial. The aim of this review was to determine the efficacy and safety of RTG on the neuropsychiatric symptoms of PD.Methods: In this systematic review and meta-analysis, PubMed, Cochrane Library, EMBASE, and Web of Science were searched for randomized controlled trials comparing RTG and placebo in PD up to May 10, 2021. We analyzed the data using Review Manager 5.2 software. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation Approach. In order to avoid false-positive results caused by random error, we use TSA software for trial sequential analysis (TSA).Results: We included 10 studies (1,844 patients). The meta-analysis showed that, compared with placebo, RTG can significantly improve the scores for Apathy Scale (MD = −1.68, 95% confidence interval, CI: −2.74 to −0.62, P = 0.002; moderate certainty), Beck Depression Inventory-II (MD = −1.19, 95% CI: −2.26 to −0.11, P = 0.03; moderate certainty), the Non-Motor Symptoms Scale (MD = −3. 66, 95% CI: −4. 30 to −3.01, P < 0.00001; moderate certainty), the sleep/fatigue domains of the Parkinson's Disease Non-motor Symptom Assessment Scale (MD = −2.03, 95% CI: −3.08 to −0.98, P = 0.0001; moderate certainty), the mood/apathy domains of the Non-motor Symptom Scale (MD = −2.48, 95% CI: −4.07 to −0.89, P = 0.002; high certainty), the eight-item Parkinson's Disease Questionnaire (MD = −4. 93, 95% CI: −6.79 to −3.07, P < 0.00001; moderate certainty), and the 39-item Parkinson's Disease Questionnaire (MD = −3.52, 95% CI: −5.25 to −1.79, P < 0.0001; high certainty). However, there was no statistically significant difference on the Snaith–Hamilton Pleasure Scale (MD = −0.12, 95% CI: −0.58 to 0.34, P = 0.61). Our results showed that RTG exerts a positive effect on sleep. According to the TSA, the results implied that, except for the Beck Depression Inventory-II, conclusive evidence have been obtained in the RTG group. It has been proven in our meta-analysis that rotigotine has good safety and tolerability.Conclusions: RTG can effectively improve the neuropsychiatric symptoms, sleep quality, and quality of life in patients with PD.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Song-bin He ◽  
Chun-yan Liu ◽  
Lin-di Chen ◽  
Zhi-nan Ye ◽  
Ya-ping Zhang ◽  
...  

Background. Previous studies suggested that visual evoked potential (VEP) was impaired in patients with Parkinson’s disease (PD), but the results were inconsistent. Methods. We conducted a systematic review and meta-analysis to explore whether the VEP was significantly different between PD patients and healthy controls. Case-control studies of PD were selected through an electronic search of the databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials. We calculated the pooled weighted mean differences (WMDs) and 95% confidence intervals (CIs) between individuals with PD and controls using the random-effects model. Results. Twenty case-control studies which met our inclusion criteria were included in the final meta-analysis. We found that the P100 latency in PD was significantly higher compared with healthy controls (pooled WMD = 6.04, 95% CI: 2.73 to 9.35, P=0.0003, n=20). However, the difference in the mean amplitude of P100 was not significant between the two groups (pooled WMD = 0.64, 95% CI: −0.06 to 1.33, P=0.07) based on 10 studies with the P100 amplitude values available. Conclusions. The higher P100 latency of VEP was observed in PD patients, relative to healthy controls. Our findings suggest that electrophysiological changes and functional defect in the visual pathway of PD patients are important to our understanding of the pathophysiology of visual involvement in PD.


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