[From MUPS to PSS: advancing insight]. / Van SOLK naar ALK.

Since 2021 experts advocate for the abolishment of the term Medically Unexplained Physical Symptoms (MUPS) and the use of Persistent Somatic Symptoms (PSS). This article elucidates the difference between MUPS and PSS, as well as the relation to other relevant concepts like functional syndromes and somatic symptom disorder. Because the term MUPS emphasizes that no somatic cause for the symptoms has been found, it is commonly concluded that the symptoms are 'psychological' in line with the body/mind dualism. This leads to excessive focus on psychosocial contributing factors in MUPS, and too little in PSS in the context of a known somatic disorder. With the term PSS, the question whether there is a somatic cause for the symptoms is not the key issue, but the persistence of the symptoms. This allows for personalised diagnostics and treatment according to the biopsychosocial model.

Non-Pharmacological Interventions for Depression and Anxiety in Parkinson's Disease.

Non-pharmacological interventions, including cognitive-behavioral therapy (CBT), non-invasive brain stimulation (NIBS), electroconvulsive therapy (ECT), light therapy (LT), and physical rehabilitation/exercise, have shown promise as effective approaches to treat symptoms of depression and anxiety in individuals with Parkinson's disease (PD). In this narrative literature overview, we discuss the state-of-the-art regarding these treatment options and address future perspectives for clinical practice and research. Non-pharmacological interventions hold promise to treat depression and anxiety in PD. There is meta-analytic evidence for the efficacy of CBT, NIBS, ECT, LT, and exercise on improving depressive symptoms. For the treatment of anxiety symptoms, CBT shows large effects but scientific evidence of other non-pharmacological interventions is limited. Importantly, these treatments are safe interventions with no or mild side-effects. More research is needed to tailor treatment to the individuals' needs and combined interventions may provide synergistic effects.We conclude that non-pharmacological interventions should be considered as alternative or augmentative treatments to pharmacological and neurosurgical approaches for the treatment of depression and anxiety in individuals with PD.

Symptom dimensions of anxiety in Parkinson's disease: Replication study in a neuropsychiatric patient population.

INTRODUCTION: Anxiety disorders occur in approximately one third of people with Parkinson's disease (PD), and have a major impact on patient and caregiver wellbeing. In order to better understand and diagnose anxiety in PD patients, we investigated the generalizability of the results of a previous factor analysis on anxiety symptoms to a sample of PD patients with neuropsychiatric symptoms. METHODS: In this cross-sectional study, anxiety symptoms were measured with the Beck Anxiety Inventory (BAI) in 123 PD patients who were referred for neuropsychiatric diagnostics and treatment. Subscales of anxiety were analyzed through principal component analysis of BAI items. The associations between BAI subscales and symptoms of motor and cognitive function and depression were assessed through regression analyses. RESULTS: Similar to the previous factor analysis, we found one psychological (affective) and four somatic subscales of anxiety in the BAI. The affective subscale was the principal component explaining 35.9% of the variance. The scores on the total BAI and the affective subscale were significantly associated with depressive symptoms. In a post-hoc analysis, the affective subscale had equal power as compared to the total BAI in predicting whether or not participants were diagnosed with an anxiety disorder after psychiatric evaluation. CONCLUSION: In this study, we replicated our previous findings of one affective and multiple somatic subscales of the BAI. The 7-item affective subscale of the BAI shows potential as a screening tool for non-episodic anxiety in PD. However, in clinical practice, we recommend evaluating anxiety symptoms in the context of other PD symptoms, including motor, autonomic, and other (neuro)psychiatric symptoms.

The Subjective Experience of Living with Parkinson's Disease: A Meta-Ethnography of Qualitative Literature.

BACKGROUND: A better understanding of the subjective experience of living with Parkinson's disease (PD) and the factors that influence this experience can be used to improve wellbeing of people with PD (PwP). OBJECTIVE: To gain more insight in the subjective experience of PD from the PwP's perspective, and the factors that contribute to this experience. METHODS: In this qualitative review, we performed a systematic search of qualitative studies discussing the subjective experience of PD and extracted reported themes (first order themes). Using a meta-ethnographic approach, we categorized the first order themes into second order themes, and created a third order construct: a holistic model of the subjective experience of living with PD. RESULTS: We included 20 studies with a total sample of 279 PwP. Data-extraction yielded 227 first order themes, which were categorized into the second order themes: 1) Awareness, 2) Disruption, 3) Adjustment, 4) The external environment, and 5) The changing self. With these themes, we developed the "model of dialectic change" which conceptualizes life with PD as a transformative journey, wherein PwP employ strategies to stabilize their changeable relationship with their external environment, while simultaneously redefining their self-concept. CONCLUSION: Our findings indicate that not only the symptoms of PD, but also the manner in which these cause disruptions in the PwP's interaction with their personal environment and self-concept, determine the subjective experience of PD andquality of life. Some PwP experience problems with adjusting, resulting in psychological distress. This calls for a holistic, multidisciplinary and participatory approach of PD.

The effects of cognitive behavioral and mindfulness-based therapies on psychological distress in patients with multiple sclerosis, Parkinson's disease and Huntington's disease: Two meta-analyses.

OBJECTIVE: Psychological distress has a high impact on quality of life in patients with multiple sclerosis (MS), Parkinson's disease (PD), and Huntington's disease (HD). Studies have shown that cognitive behavioral therapy (CBT) and mindfulness-based therapies (MBTs) are successful in reducing psychological distress in patients with anxiety, depressive, and chronic somatic disorders. We aimed to investigate the effectiveness of these therapies in MS, PD, and HD patients. METHODS: We performed a comprehensive literature search in PubMed, PsycINFO, Embase and the Cochrane Central Register of Controlled Trials up to March 2018. Randomized controlled trials (RCTs) investigating a CBT or MBT and reporting psychological outcome measures were included. Two separate meta-analyses were performed; one on studies comparing psychological therapy with a treatment as usual or waitlist condition and one on studies with active treatment control conditions. RESULTS: The first meta-analysis (N = 12 studies, 8 in MS and 4 in PD populations) showed a significant effect size of g = 0.51 in reducing psychological distress. The second meta-analysis (N = 7 studies, in MS populations) showed a mean effect size of g = 0.36. No RCTs were found in HD populations. The overall quality of the included studies was low and considerable heterogeneity was found. No evidence was found for publication bias. CONCLUSION: CBT and MBTs have a small to moderate effect on reducing psychological distress in patients with PD and MS. However, more research with better methodological quality and larger study samples is warranted, especially in HD patient populations.

Bright light therapy for depression in Parkinson disease: A randomized controlled trial.

OBJECTIVE: To assess the efficacy of bright light therapy (BLT) in reducing depressive symptoms in patients with Parkinson disease (PD) and major depressive disorder (MDD) compared to a control light. METHODS: In this double-blind controlled trial, we randomized patients with PD and MDD to treatment with BLT (±10,000 lux) or a control light (±200 lux). Participants were treated for 3 months, followed by a 6-month naturalistic follow-up. The primary outcome of the study was the Hamilton Depression Rating Scale (HDRS) score. Secondary outcomes were objective and subjective sleep measures and salivary melatonin and cortisol concentrations. Assessments were repeated halfway, at the end of treatment, and 1, 3, and 6 months after treatment. Data were analyzed with a linear mixed-model analysis. RESULTS: We enrolled 83 participants. HDRS scores decreased in both groups without a significant between-group difference at the end of treatment. Subjective sleep quality improved in both groups, with a larger improvement in the BLT group (B [SE] = 0.32 [0.16], p = 0.04). Total salivary cortisol secretion decreased in the BLT group, while it increased in the control group (B [SE] = -8.11 [3.93], p = 0.04). CONCLUSION: BLT was not more effective in reducing depressive symptoms than a control light. Mood and subjective sleep improved in both groups. BLT was more effective in improving subjective sleep quality than control light, possibly through a BLT-induced decrease in cortisol levels. CLINICALTRIALSGOV IDENTIFIER: NCT01604876. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that BLT is not superior to a control light device in reducing depressive symptoms in patients with PD with MDD.

Body awareness training in the treatment of wearing-off related anxiety in patients with Parkinson's disease: Results from a pilot randomized controlled trial.

BACKGROUND: In Parkinson's disease (PD) patients, fluctuations in symptoms commonly occur after many years of dopamine replacement therapy. The so-called wearing-off phenomenon exists of both motor and non-motor symptoms, such as rigidity and anxiety. Current treatment options are limited and an integrated approach is needed to address the complex interactions between motor and non-motor symptoms. Since wearing-off is eventually inevitable, treatment needs to focus on coping, acceptance and self-efficacy. We developed the body awareness training, named BEWARE, combining physical therapy with acceptance and commitment therapy to help PD patients deal better with wearing-off related anxiety (WRA). METHODS: This was an investigator-blinded randomized controlled trial. Forty PD patients with WRA were randomly assigned to the BEWARE or to the treatment as usual (TAU) condition. Assessments were performed prior to and immediately after the treatment period, and at 3-months follow up. The primary outcome was self-efficacy, secondary outcomes focused on mobility, daily functioning, anxiety, depression and quality of life. RESULTS: There was no significant improvement in self-efficacy in the BEWARE treatment condition when compared to TAU. However, standing balance and emotional wellbeing showed a significant improvement, and feelings of stigmatization showed a trend-significant decrease in the BEWARE condition. CONCLUSIONS: We consider the BEWARE training to be a promising therapeutic approach to address WRA. Improvement points from the participants included 1) less frequent but longer therapy sessions; 2) active involvement of caregivers; and 3) the development of a supportive workbook. The optimized treatment protocol needs further evaluation in a phase III RCT. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02054845.

Predictors of anxiety in early-stage Parkinson's disease - Results from the first two years of a prospective cohort study.

AIM: Anxiety has a negative impact on daily functioning and quality of life in patients with Parkinson's disease (PD). This study aims at assessing which sociodemographic and clinical characteristics predict the course of anxiety in early PD. METHODS: The participants of this two-year prospective cohort study were recently diagnosed PD patients not receiving psychiatric medications or dopamine replacement therapy at baseline. Assessments were performed annually after baseline. The primary outcome measure was anxiety, as measured with the State-Trait Anxiety Inventory (STAI). Covariates were age, gender, family history, striatal dopamine transporter binding ratios, and severity of motor and non-motor features of PD at baseline. Data were analyzed using a mixed model analysis. RESULTS: Inclusion criteria were met by 306 subjects. An increase in STAI total score was predicted by older age, lower score on the Montreal Cognitive Assessment, and the presence of a probable REM-sleep behavior disorder (RBD) at baseline. A decrease in STAI total score over time was predicted by a higher baseline score on the 15-item Geriatric Depression Scale, compulsive behavior at baseline and a family history of PD. CONCLUSIONS: More severe baseline anxiety was associated with compulsive behavior and depressive symptoms. These symptoms had a parallel course, showing a decrease over time. An increase in anxiety was predicted by older age, worse cognitive functioning and the presence of RBD. Our findings, when replicated in a sample of PD patients in a more advanced disease stage, could provide starting points for prevention of anxiety in PD patients.

The bidirectional longitudinal relationship between insomnia, depression and anxiety in patients with early-stage, medication-naïve Parkinson's disease.

INTRODUCTION: While anxiety, depression and insomnia frequently (co-)occur in Parkinson's disease (PD) patients, little is known about their temporal relationship. In this study, we tested two hypotheses: i) insomnia predicts an increase in symptoms of depression or anxiety and ii) anxiety or depression at baseline predicts insomnia in PD patients six months later. METHODS: We used longitudinal data from a prospective cohort study of early-stage, medication-naïve PD patients. Primary outcome measures were: anxiety symptoms, measured with the State-Trait Anxiety Inventory (STAI); depressive symptoms, measured with the 15-item Geriatric Depression Scale (GDS-15); and insomnia, defined as a score ≥ 2 on item 1.7 of the Movement Disorder Society - Unified Parkinson's Disease Rating Scale. We performed linear and logistic regression analyses, correcting for baseline value of the respective outcome variable. RESULTS: Baseline insomnia was not associated with GDS-15 or STAI total score at follow-up. In a post hoc analysis, we found that insomnia predicted a higher STAI State score (B(SE) = 2.50 (1.07), p < 0.05), while the association with the STAI Trait score was not significant. Baseline STAI scores (B(SE) = 0.02 (0.01), p = 0.001) and GDS-15 score (B(SE) = 0.15 (0.05), p < 0.001) were significantly associated with insomnia at follow-up. CONCLUSION: Symptoms of anxiety and depression may constitute a risk factor for insomnia in PD. The relationship between insomnia and anxiety is bidirectional, which suggests that both anxiety and sleep disorders can start a negative spiral in PD patients, where one enhances the other. Independent clinical attention for these symptoms in PD patients is therefore warranted.

A double-blind randomized controlled trial to assess the effect of bright light therapy on depression in patients with Parkinson's disease.

BACKGROUND: A disturbed circadian rhythm seems to be a causal factor in the occurrence of depressive disorders in patients with Parkinson's disease (PD). The circadian rhythm can be restored with light. Therefore, Bright Light Therapy (BLT) might be a new treatment option for depression in PD patients. METHODS/DESIGN: In this double-blind controlled trial, 84 subjects with idiopathic PD are randomized to either BLT or a control light condition. The BLT condition emits white light with an intensity of 10,000 Lux, while the control device emits dim white light of 200 Lux, which is presumed to be too low to influence the circadian rhythm. Subjects receive 30 min of home treatment twice daily for three months. Timing of treatment is based on the individual chronotype. After finishing treatment, subjects enter a follow-up period of six months. The primary outcome of the study is the severity of depressive symptoms, as measured with the Hamilton Depression Rating Scale. Secondary outcomes are alternative depression measures, objective and subjective sleep measures, and salivary melatonin and cortisol concentrations. For exploratory purposes, we also assess the effects on motor symptoms, global cognitive function, comorbid psychiatric disorders, quality of life and caregiver burden. Data will be analyzed using a linear mixed models analysis. DISCUSSION: Performing a placebo-controlled trial on the effects of BLT in PD patients is challenging, as the appearance of the light may provide clues on the treatment condition. Moreover, fixed treatment times lead to an improved sleep-wake rhythm, which also influences the circadian system. With our study design, we do not compare BLT to placebo treatment, i.e. an ineffective control treatment. Rather, we compare structuring of the sleep-wake cycle in both conditions with additional BLT in the experimental condition, and additional dim light in the control condition. Participants are not informed about the exact details of the two light devices and the expected therapeutic effect, and expectancies are rated prior to the start of treatment. Ideally, the design of a future study on BLT should include two extra treatment arms where BLT and control light are administered at random times. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov on May 17th 2012 (ClinicalTrials.gov Identifier: NCT01604876 ).

A smaller amygdala is associated with anxiety in Parkinson's disease: a combined FreeSurfer-VBM study.

BACKGROUND: Up to 50% of all patients with Parkinson's disease (PD) suffer from anxiety symptoms, a much higher percentage than in the general population. This suggests that PD associated pathological alterations partly underlie these symptoms, although empirical evidence is limited. METHODS: Here we investigated the association between anxiety symptoms measured with the Beck Anxiety Inventory (BAI) and hippocampal and amygdalar volume in 110 early-stage patients with PD. Measures of anxiety in PD are often obscured by overlap with the somatic symptoms. We therefore also used a subscale of the BAI, established by our recent factor analysis, that reflects 'psychological' anxiety symptoms and is independent of the severity of PD-related motor and autonomic symptoms. We used FreeSurfer and voxel-based morphometry for the volumetric analyses. RESULTS: Both software packages showed a negative correlation between the 'psychological' subscale of the BAI, but not total BAI and volume of the left amygdala, independent of the severity of motor symptoms, autonomic dysfunction and dopaminergic or anxiolytic medication status. CONCLUSIONS: These results confirm studies in non-PD samples showing lower left amygdalar volume in anxious patients. The results also indicate that the 'psychological' BAI subscale is a better reflection of neural correlates of anxiety in PD. Whether the left amygdalar volume decrease constitutes a premorbid trait, a PD-associated neurobiological susceptibility to anxiety or arises as a consequence of chronic anxiety symptoms remains to be determined by future prospective longitudinal studies. Nonetheless, we speculate that the Parkinson pathology is responsible for the reduction in amygdalar volume and the concomitant development of anxiety symptoms.

BEWARE: Body awareness training in the treatment of wearing-off related anxiety in patients with Parkinson's disease: study protocol for a randomized controlled trial.

BACKGROUND: The wearing-off phenomenon in patients with Parkinson's disease (PD) is a complication of prolonged levodopa usage. During this phenomenon, motor symptoms such as rigidity and freezing re-emerge. This is often accompanied by non-motor symptoms, including anxiety, the so-called wearing-off related anxiety (WRA). Current treatment options are limited and typically focus on either the physical or mental aspects of wearing-off. An integrated approach seems warranted in order to optimally address the complex reciprocal interactions between these aspects. Also, because wearing-off is eventually inescapable, treatment needs to focus on coping, acceptance, and self-efficacy. We therefore developed an integrated body awareness intervention, combining principles from physical therapy with acceptance and commitment therapy to teach patients to deal with WRA. This study will investigate whether this new intervention, named BEWARE, is more effective than treatment as usual in increasing self-efficacy. METHODS/DESIGN: This is a single-blinded randomized controlled trial in 36 PD patients who experience WRA. Subjects will be recruited from the outpatient clinic for movement disorders of the VU University Medical Center. After providing written informed consent, patients will be randomly assigned to an experimental (BEWARE) or treatment-as-usual (physical therapy) group. Clinical assessments will be performed prior to the intervention, directly after the 6-week intervention period, and at 3-month naturalistic follow-up by a blinded investigator not involved in the study. The primary outcome measure is self-efficacy, and secondary outcomes focus on mobility, daily functioning, anxiety, and quality of life. DISCUSSION: Because wearing-off is an inevitable consequence of levodopa therapy and current treatment options are insufficient, a multidisciplinary intervention that addresses both physical and mental aspects of wearing-off in PD may foster additional benefits for treating WRA in PD patients over mono-disciplinary care alone. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02054845. Date of registration: 30 January 2014.

Anxiety in Parkinson's disease: Symptom dimensions and overlap with depression and autonomic failure.

INTRODUCTION: Anxiety disorders are highly prevalent in patients with Parkinson's disease (PD) and have a major impact on wellbeing. They nevertheless receive limited scientific attention. This study aimed to establish the symptom dimensions of anxiety in PD, and their relationship with depression, autonomic failure and motor symptoms. METHODS: In this cross-sectional observational study, symptoms of anxiety were measured with the Beck Anxiety Inventory (BAI) in 294 PD patients. Symptom dimensions of anxiety in PD were explored through principal component analysis (PCA) of BAI items. The relationship between anxiety and depressive, autonomic and motor symptoms was assessed through PCA and regression analyses. RESULTS: Clinically relevant symptoms of anxiety were present in 45% of patients. PCA of the BAI resulted in five subscales, corresponding to a single affective and four somatic symptom dimensions (thermoregulation, hypotension, hyperventilation and trembling) of anxiety. Symptoms of anxiety and depression displayed a large overlap. All somatic BAI subscales were significantly influenced by motor and autonomic symptoms, while the affective subscale was not. CONCLUSION: Anxiety in PD comprises affective and somatic symptom dimensions. The affective subscale of the BAI is not influenced by motor or autonomic symptoms, and may therefore prove useful for future research. Scores on the somatic subscales of the BAI were associated with autonomic failure and motor impairment, demonstrating a strong interplay between motor and non-motor symptoms in PD. These results stress the importance of a holistic approach of anxiety in PD.

Depression and impulse control disorders in Parkinson's disease: two sides of the same coin?

Depression and impulse control disorders (ICD) are two common neuropsychiatric features in Parkinson's disease (PD). Studies have revealed that both phenomena are associated with aberrations in ventral striatal dopamine signaling and concomitant dysfunction of the reward-related (limbic) cortico-striatal-thalamocortical (CSTC) circuit. Depression in PD seems associated with decreased activity in the limbic CSTC circuit, whereas ICD seem associated with increased limbic CSTC circuit activity, usually after commencing dopamine replacement therapy (DRT). Not all DRT using PD patients, however, develop symptoms of ICD, suggesting an additional underlying neurobiological susceptibility. Furthermore, the symptoms of depression and ICD frequently coincide even though they are related to seemingly contrasting limbic CSTC circuit activation states. The aim of this review is to provide an overview of the currently available literature on the neurobiology of PD-related depression and ICD and discusses possible susceptibility factors. Finally, we propose a neurobiological model that identifies ventral striatal dopaminergic denervation as a common underlying neurobiological substrate of depression and ICD and subsequent dysfunction of reward and motivation-related brain areas.

[Atypical presentation of delirium: risk of misdiagnosis and undertreatment]. / Atypisch delier: gevaar voor onderdiagnostiek en -behandeling.

An atypical presentation of delirium increases the risk of misdiagnosis and undertreatment. Three cases are presented in this article. A 65-year-old woman, admitted for malnutrition, has significant mood-related symptoms that resemble depression. A 50-year-old male, admitted with an abscess, necrotizing fasciitis and sepsis, appears to be suicidal. A 61-year-old male, admitted with pneumonia, has auditory hallucinations. All three patients turned out to have a delirium. The authors advise ruling out a delirium in all patients who have predisposing factors and who develop an acute psychiatric disorder while staying in the hospital, before considering other psychiatric diagnoses. Advice on how to improve the diagnostic process is given.

Bright light therapy in Parkinson's disease: an overview of the background and evidence.

Sleep disorders are common in Parkinson's disease (PD) and seem to be strongly associated with depression. It has been suggested that sleep disorders as well as depression are caused by a disturbed circadian rhythm. Indeed, PD patients are prone to misalignment of their circadian rhythm due to various factors, and many patients with PD display a phase advance of their circadian rhythm. Current treatment options for sleep disorders and depression in patients with PD are limited and can have serious side effects; alternative treatments are therefore badly needed. Bright light therapy (BLT) restores circadian rhythmicity effectively in mood- and sleep-disturbed patients without PD. The few studies that focused on the efficacy of BLT in patients with PD demonstrated a positive effect of BLT not only on sleep and mood but also on motor function. More research on the neurobiology and efficacy of BLT in PD is warranted.

Changes in quality of life after balloon treatment followed by gastric banding in severely obese patients--the use of two different quality of life questionnaires.

BACKGROUND: Improvements in quality of life (QOL) obtained by weight loss have mainly been reported after bariatric surgery. QOL has not been investigated in surgical patients first losing weight by nonsurgical means followed by a surgical intervention and never simultaneously by two QOL-a generic and a disease-specific-questionnaires. METHODS: Prospective data were obtained from 40 consecutive patients (mean age 36.6 years, body weight 142.4 kg, body mass index (BMI) 46.5 kg/m2). Two different QOL questionnaires, the generic Medical Outcomes Study Short Form-36 (SF-36) and the disease-specific Health-Related Quality of Life (HRQL) questionnaire, were evaluated at three points in time: at the start, 3 months after the placement of an intragastric balloon that remained in situ for 6 months, and 3 months after subsequent gastric banding. RESULTS: QOL scores revealed a significant improvement in many health domains, with an earlier improvement with the disease-specific HRQL, whereas the generic QOL questionnaire lagged behind. However, in the end, the SF-36 caught up completely to normal-weight levels, whereas some scales of the HRQL remained below these levels. Work productivity and involvement in sports improved significantly. BMI declined significantly over time, but no correlation with SF-36 and HRQL score changes was found. CONCLUSION: The QOL improved substantially independent of changes in BMI. Because of the divergent outcomes of generic and disease-specific QOL questionnaires, prospective studies should examine the sensitivity to changes of both kinds of QOL questionnaires.