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Introduction Differences in brain network connectivity may reflect the capability of the neurological substrate to compensate for brain damage and preserve cognitive function (cognitive reserve). We examined the associations between white matter connectivity, brain damage markers, and cognition in a population sample of middle-aged individuals. Methods A total of 4759 participants from The Maastricht Study (mean age = 59.2, SD = 8.7, 50.2% male) underwent cognitive testing and diffusion magnetic resonance imaging (dMRI), from which brain volume, structural connectivity, and vascular damage were quantified. Multivariable linear regression was used to investigate whether connectivity modified the association between brain damage and cognition, adjusted for demographic and cardiometabolic risk factors. Results More atrophic and vascular brain damage was associated with worse cognition scores. Increasing connectivity moderated the negative association between damage and cognition (chi(2) = 8.64, df = 3, p

BackgroundEvidence is lacking to what extent patients with Whiplash-Associated Disorders (WAD), those with non-traumatic neck pain (NTNP), and pain-free individuals differ regarding type and severity of impairments, disability, and psychological factors.Objective To compare clinical characteristics between patients with WAD, with NTNP, and pain-free individuals in primary care physiotherapy. Additionally, differences between patient groups for both acute and chronic symptoms were assessed.MethodA cross-sectional study was conducted including 168 patients with WAD, 336 matched patients with NTNP, and 336 pain-free individuals. Differences and prevalence rates were calculated for pain intensity, pain distribution, cervical range of motion, neck flexor muscle endurance, self-reported disability, and psychological factors.Results Patients with WAD had higher pain intensity (median 6/10 vs. 5/10 p83%) scored in the normal range. No significant differences between the patient groups were observed (p>.16). Both patient groups scored significantly worse than pain-free individuals on all characteristics. Patients with WAD and NTNP experienced different types of activity limitations and participation restrictions.ConclusionWAD is a more severe condition than NTNP and should be considered a separate subgroup. A different approach in clinical practice and research is required for WAD and NTNP.

BACKGROUND: The 'dual syndrome' hypothesis states that two cognitive subtypes can be distinguished in mild cognitive impairment in Parkinson's disease (PD-MCI): a frontostriatal one, characterized by attentional and/or executive deficits, and a posterior cortical one, characterized by visuospatial, memory and/or language deficits. The latter type has been associated with a higher risk of earlier development of PD dementia. The functional bases of these subtypes remain partly unknown.OBJECTIVE: To identify EEG modifications associated with PD-MCI subtypes.METHODS: 75 non-demented PD patients underwent a comprehensive neuropsychological assessment and a high-density EEG. They were classified as having normal cognition (PD-NC; n = 37), PD-MCI with a frontostriatal subtype (PD-FS; n = 11) or PD-MCI with a posterior cortical subtype (PD-PC; n = 27). Two EEG analyses were performed: (a) spectral powers quantification and (b) functional connectivity analysis.RESULTS: PD-FS patients displayed spectral and functional EEG alterations, namely (a) higher powers in the theta and delta bands, (b) lower powers in the beta2 band and (c) lower functional connectivity in the beta2 band compared to PD-NC and PD-PC patients. These alterations were mainly located in the frontal, limbic and parietal regions. There were no significant differences between PD-NC and PD-PC.CONCLUSION: EEG alterations previously reported in PD-MCI may only concern the frontostriatal subtype, and not the posterior-cortical subtype. This provides evidence for the dual syndrome hypothesis and emphasizes the importance of identifying PD-MCI subtypes. It also shows the promising potential of EEG to discriminate between PD-MCI subtypes.

Background and Hypothesis There is a substantial gap in life expectancy between patients with severe mental illness (SMI) and the general population and it is important to understand which factors contribute to this difference. Research suggests an association between tardive dyskinesia (TD) and mortality; however, results are inconclusive. In addition, studies investigating associations between parkinsonism or akathisia and mortality are rare. We hypothesized that TD would be a risk factor for mortality in patients with SMI. Study Design We studied a cohort of 157 patients diagnosed predominantly with schizophrenia on the former Netherlands Antilles. TD, parkinsonism, and akathisia were assessed with rating scales on eight occasions over a period of 18 years. Twenty-four years after baseline, survival status and if applicable date of death were determined. Associations between movement disorders and survival were analyzed using Cox regression. Sex, age, antipsychotics, antidepressants and benzodiazepines at each measurement occasion were tested as covariates. Study Results Parkinsonism was a significant risk factor with an HR of 1.02 per point on the motor subscale of the Unified Parkinson’s Disease Rating Scale (range 0–56). TD and akathisia were not significantly associated with mortality. Conclusions Parkinsonism may be an important risk factor for mortality in SMI patients. This finding calls for more follow-up and intervention studies to confirm this finding and to explore whether treatment or prevention of parkinsonism can reduce excess mortality.

BACKGROUND: There is little evidence to support the use of antipsychotic polypharmacy, and there are concerns about safety and side effects. Nonetheless, it is commonly used in the treatment of long-term inpatients with schizophrenia. This study investigated the effects of switching from a combination of first- and second-generation antipsychotics (FGA and SGA) to monotherapy (FGA or SGA) on relapse rates and psychiatric symptomatology.METHODS: Institutionalized patients with chronic psychotic disorders using a combination of SGA and FGA (n = 136) participated in a randomized open-label trial. The SWITCH group discontinued either FGA or SGA, the STAY group continued combination treatment. Relapse and psychotic symptoms were measured at baseline and during follow-up at 3, 6, and 9 months. Psychiatric symptomatology was measured using the Brief Psychiatric Rating Scale (BPRS). Relapse was defined as (i) an increase in BPRS score of at least 2 points on any item, or (ii) an increase of at least 4 points in total BPRS score and an adjustment of antipsychotics.RESULTS: A logistic regression model, corrected for sex, showed that the probability of relapse was significantly lower in the SWITCH group: 0.29 (95% CI 0.13-0.62). The protective effect of switching to monotherapy was attributable to patients continuing clozapine as monotherapy. For patients who did not experience a relapse nor dropped out, BPRS total scores decreased significantly more in the SWITCH group (p = 0.0001).CONCLUSION: Switching from a combination of FGA and SGA to monotherapy in long-term inpatients does not increase the relapse rate and may even reduce it.

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.

Background The number of patients with proton pump inhibitor (PPI)-refractory reflux symptoms is underestimated since many patients resign after an unsuccessful therapy attempt. Thus, it would be useful having a non-invasive tool that can help identify true gastroesophageal reflux disease (GERD) patients in order to manage them early and properly. The GerdQ is a validated tool developed for this purpose but its applicability in PPI-refractory patients has not yet been investigated. Our aim was to investigate if reflux symptoms per se, the GerdQ and patients characteristics are suitable for non-invasive diagnosis of GERD in patients with PPI refractory reflux symptoms. Methods A total of 500 patients from a prospectively recorded data base with PPI-refractory reflux symptoms were retrospectively analyzed. All patients received comprehensive diagnostic workup including EGD, pH-impedance measurement and manometry. GERD was diagnosed according to the recent Lyon consensus. Results Of all patients enrolled in the study, 280 (56%) finally fulfilled the criteria for objectively verified GERD according to the Lyon consensus. There were no significant differences in age and gender between the patients with and without GERD, whereas the body mass index was significantly higher in the group with verified GERD, but the discriminative value was low (Welch-Test, p Conclusion Based on our study, neither symptoms and the GerdQ score nor patients’ characteristics are appropriate tools to distinguish between GERD and other causes for reflux symptoms in patients with PPI-refractory reflux symptoms.

Background The "dual syndrome hypothesis" distinguished two subtypes in mild cognitive impairment (MCI) in Parkinson's disease: frontostriatal, characterized by attentional and executive deficits; and posterior cortical, characterized by visuospatial, memory, and language deficits. Objective The aim was to identify resting-state functional modifications associated with these subtypes. Methods Ninety-five nondemented patients categorized as having normal cognition (n = 31), frontostriatal (n = 14), posterior cortical (n = 20), or mixed (n = 30) cognitive subtype had a 3 T resting-state functional magnetic resonance imaging scan. Twenty-four age-matched healthy controls (HCs) were also included. A group-level independent component analysis was performed to identify resting-state networks, and the selected components were subdivided into 564 cortical regions in addition to 26 basal ganglia regions. Global intra- and inter-network connectivity along with global and local efficiencies was compared between groups. The network-based statistics approach was used to identify connections significantly different between groups. Results Patients with posterior cortical deficits had increased intra-network functional connectivity (FC) within the basal ganglia network compared with patients with frontostriatal deficits. Patients with frontostriatal deficits had reduced inter-network FC between several networks, including the visual, default-mode, sensorimotor, salience, dorsal attentional, basal ganglia, and frontoparietal networks, compared with HCs, patients with normal cognition, and patients with a posterior cortical subtype. Similar results were also found between patients with a mixed subtype and HCs. Conclusion MCI subtypes are associated with specific changes in resting-state FC. Longitudinal studies are needed to determine the predictive potential of these markers regarding the risk of developing dementia. (c) 2021 International Parkinson and Movement Disorder Society

Objective: The Hamilton Depression Rating Scale (HDRS-17) and the Hamilton Anxiety Rating Scale (HARS-14) have been acknowledged as gold standards in evaluating the severity of depression and anxiety. The specificity and sensitivity of these scales in predicting somatic complaints of depression and anxiety are issues in both clinical and research areas. The present study proposes a new model to enhance the sensitivity and specificity of HDRS-17 and HARS-14 for predicting symptoms of insomnia, inappetence, and loss of libido in psychiatric patients. Methods: This study included 1507 patients diagnosed with bipolar disorder, depression, panic disorder, obsessive-compulsive disorder, and generalized anxiety disorder. The HDRS-17 and the HARS-14 were utilized as predictive scales for the prediction of patients' sleep, appetite, and libido. The sensitivity and specificity were computed using the receiver operating characteristic (ROC). Logistic regression was performed to enhance the predictive values. The predictive value of the logistic regression model was not satisfactory, and a conversion table was therefore designed for each symptom-diagnosis subgroup. The new joint ROC model was then used to recalculate the sensitivity and specificity of the 2 scales for each symptom-diagnosis subgroup. The outcome is a prediction table, presented for use by clinicians. Results: It was observed that the new statistical model, the joint ROC, increased the sensitivity and specificity of the HDRS-17 and the HARS-14. Conclusion: Based on the results of the evaluations with the HDRS and the HARS, the joint ROC method was developed to better predict the presence of symptoms.

Bipolar patients (BD) in the euthymic phase show almost no symptoms, nevertheless possibility of relapse is still present. We expected to find a psychobiological trace of their vulnerability by analyzing a specific network-the Language Network (LN)-connecting many high-level processes and brain regions measured at rest. According to Crow's hypothesis on the key role of language in the origin of psychoses, we expected an altered asymmetry of the LN in euthymic BDs. Eighteen euthymic BD patients (10 females; age = 54.50 ± 11.38 years) and 16 healthy controls (HC) (8 females; age = 51.16 ± 11.44 years) underwent a functional magnetic resonance imaging scan at rest. The LN was extracted through independent component analysis. Then, LN time series was used to compute the fractional amplitude of the low-frequency fluctuation (fALFF) index, which was then correlated with clinical scales. Compared with HC, euthymic patients showed an altered LN with greater activation of Broca's area right homologous and anterior insula together with reduced activation of left middle temporal gyrus. The normalized fALFF analysis on BD patients' LN time series revealed that the Slow-5 fALFF band was positively correlated with residual mania symptoms but negatively associated with depression scores. In line with Crow's hypothesis postulating an altered language hemispheric asymmetry in psychoses, we revealed, in euthymic BD patients, a right shift involving both the temporal and frontal linguistic hubs. The fALFF applied to LN allowed us to highlight a number of significant correlations of this measure with residual mania and depression psychiatric symptoms. ispartof: TRANSLATIONAL PSYCHIATRY vol:12 issue:1 ispartof: location:United States status: published

Background Bipolar disorder (BD) is one of the leading causes of disability worldwide. However, the prevalence and predictors of long-term work disability among patients with type I and II BD have scarcely been studied. We investigated the clinical predictors of long-term work disability among patients with BD. Methods The Jorvi Bipolar Study (JoBS) is a naturalistic prospective cohort study (n = 191) of adult psychiatric in- and out-patients with DSM-IV type I and II BD in three Finnish cities. Within JoBS we examined the prevalence and predictors of disability pension being granted during a six-year follow-up of the 152 patients in the labor force at baseline and collected information on granted pensions from national registers. We determined the predictors of disability pension using logistic regression models. Results Over the 6 years, 44% of the patients belonging to the labor force at baseline were granted a disability pension. Older age; type I BD; comorbidity with generalized anxiety disorder, post-traumatic stress disorder or avoidant personality disorder; and duration of time with depressive or mixed symptoms predicted disability pensions. Including disability pensions granted before baseline increased their total prevalence to 55.5%. The observed predictors were similar. Conclusion This regionally representative long-term prospective study found that about half of patients with type I or II bipolar disorder suffer from persistent work disability that leads to disability pension. In addition to the severity of the clinical course and type I bipolar disorder, the longitudinal accumulation of time depressed, psychiatric comorbidity, and older age predicted pensioning.

Caregivers are often encouraged to praise children to reduce externalizing behavior. Although several theoretical perspectives suggest that praise works (e.g., praise reinforces positive behavior), others suggest it may not (e.g., children dismiss praise or experience it as controlling). This longitudinal-observational study examined whether (a) caregivers' praise and children's externalizing behavior were related; (b) an evidence-based parenting program increased caregivers' praise; (c) and increasing praise reduced children's externalizing behavior. Participants (387 caregiver-child dyads) were randomly assigned to a 14-session parenting program (aiming to improve parenting behavior, partly via praise) or a control group. Children (aged 4-8 years, 45% girls) scored at or above the 75th percentile on externalizing behavior problems. Caregivers (91% Caucasian, 85% born in the Netherlands, 50.5% highly educated) were mostly mothers (91%). At baseline, postintervention, and follow-up, we assessed caregivers' labeled and unlabeled praise via in-home observations, and children's externalizing behavior via caregiver-reports and observations. At baseline, caregivers' unlabeled praise was related to more (rather than less) externalizing behavior. The parenting program successfully increased praise and reduced caregiver-reported (but not observed) externalizing behavior; importantly, however, praise did not mediate the program's effect on caregiver-reported externalizing behavior. Although the program did not directly reduce observed externalizing behavior, it did so indirectly via labeled praise. Our results suggest that, although praise and externalizing child behavior are related, praise may not be a key mechanism underlying the effects of the parenting program. If praise has beneficial effects on children's externalizing behavior, these effects are probably limited to labeled praise. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Stereotactic lesioning of the bilateral globus pallidus (GPi) was one of the first surgical treatments for medication-refractory dystonia but has largely been abandoned in clinical practice after the introduction of deep brain stimulation (DBS). However, some patients with dystonia are not eligible for DBS. Therefore, we reviewed the efficacy, safety, and sustainability of bilateral pallidotomy by conducting a systematic review of individual patient data (IPD). Guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and IPD were followed. In May 2020, Medline, Embase, Web of Science, and Cochrane Library were searched for studies reporting on outcome of bilateral pallidotomy for dystonia. If available, IPD were collected. In this systematic review, 100 patients from 33 articles were evaluated. Adverse events were reported in 20 patients (20%), of which 8 were permanent (8%). Pre-and postoperative Burke-Fahn-Marsden Dystonia Rating Movement Scale scores were available for 53 patients. A clinically relevant improvement (>20%) of this score was found in 42 of 53 patients (79%). Twenty-five patients with status dystonicus (SD) were described. In all but 2 the SD resolved after bilateral pallidotomy. Seven patients experienced a relapse of SD. Median-reported follow-up was 12 months (n = 83; range: 2-180 months). Based on the current literature, bilateral pallidotomy is an effective and relatively safe procedure for certain types of dystonia, particularly in medication-refractory SD. Although due to publication bias the underreporting of negative outcomes is very likely, bilateral pallidotomy is a reasonable alternative to DBS in selected dystonia patients. (c) 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The current management of patients with primary psychosis worldwide is often remarkably stereotyped. In almost all cases an antipsychotic medica­tion is prescribed, with second-generation antipsychotics usually preferred to first-generation ones. Cognitive behavioral therapy is rarely used in the vast majority of countries, although there is evidence to support its efficacy. Psychosocial interventions are often provided, especially in chronic cases, but those applied are frequently not validated by research. Evidence-based family interventions and supported employment programs are seldom implemented in ordinary practice. Although the notion that patients with primary psychosis are at increased risk for cardiovascular diseases and diabetes mellitus is widely shared, it is not frequent that appropriate measures be implemented to address this problem. The view that the management of the patient with primary psychosis should be personalized is endorsed by the vast majority of clinicians, but this personalization is lacking or inadequate in most clinical contexts. Although many mental health services would declare themselves “recovery-oriented”, it is not common that a focus on empowerment, identity, meaning and resilience is ensured in ordinary practice. The present paper aims to address this situation. It describes systematically the salient domains that should be considered in the characterization of the individual patient with primary psychosis aimed at personalization of management. These include positive and negative symptom dimensions, other psychopathological components, onset and course, neurocognition and social cognition, neurodevelopmental indicators; social functioning, quality of life and unmet needs; clinical staging, antecedent and concomitant psychiatric conditions, physical comorbidities, family history, history of obstetric complications, early and recent environmental exposures, protective factors and resilience, and internalized stigma. For each domain, simple assessment instruments are identified that could be considered for use in clinical practice and included in standardized decision tools. A management of primary psychosis is encouraged which takes into account all the available treatment modalities whose efficacy is supported by research evidence, selects and modulates them in the individual patient on the basis of the clinical characterization, addresses the patient’s needs in terms of employment, housing, self-care, social relationships and education, and offers a focus on identity, meaning and resilience.

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.

Stereotactic lesioning of the bilateral globus pallidus (GPi) was one of the first surgical treatments for medication‐refractory dystonia but has largely been abandoned in clinical practice after the introduction of deep brain stimulation (DBS). However, some patients with dystonia are not eligible for DBS. Therefore, we reviewed the efficacy, safety, and sustainability of bilateral pallidotomy by conducting a systematic review of individual patient data (IPD). Guidelines of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses and IPD were followed. In May 2020, Medline, Embase, Web of Science, and Cochrane Library were searched for studies reporting on outcome of bilateral pallidotomy for dystonia. If available, IPD were collected. In this systematic review, 100 patients from 33 articles were evaluated. Adverse events were reported in 20 patients (20%), of which 8 were permanent (8%). Pre‐and postoperative Burke‐Fahn‐Marsden Dystonia Rating Movement Scale scores were available for 53 patients. A clinically relevant improvement (>20%) of this score was found in 42 of 53 patients (79%). Twenty‐five patients with status dystonicus (SD) were described. In all but 2 the SD resolved after bilateral pallidotomy. Seven patients experienced a relapse of SD. Median‐reported follow‐up was 12 months (n = 83; range: 2–180 months). Based on the current literature, bilateral pallidotomy is an effective and relatively safe procedure for certain types of dystonia, particularly in medication‐refractory SD. Although due to publication bias the underreporting of negative outcomes is very likely, bilateral pallidotomy is a reasonable alternative to DBS in selected dystonia patients. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Over the last three decades, movement disorder as well as sensorimotor and psychomotor functioning in schizophrenia (SZ) and other psychoses has gained greater scientific and clinical relevance as an intrinsic component of the disease process of psychotic illness; this extends to early psychosis prediction, early detection of motor side effects of antipsychotic medication, clinical outcome monitoring, treatment of psychomotor syndromes (e.g. catatonia), and identification of new targets for non-invasive brain stimulation. In 2017, a systematic cooperation between working groups interested in movement disorder and sensorimotor/psychomotor functioning in psychoses was initiated across European universities. As a first step, the members of this group would like to introduce and define the theoretical aspects of the sensorimotor domain in SZ and other psychoses. This consensus paper is based on a synthesis of scientific evidence, good clinical practice and expert opinions that were discussed during recent conferences hosted by national and international psychiatric associations. While reviewing and discussing the recent theoretical and experimental work on neural mechanisms and clinical implications of sensorimotor behavior, we here seek to define the key principles and elements of research on movement disorder and sensorimotor/psychomotor functioning in psychotic illness. Finally, the members of this European group anticipate that this consensus paper will stimulate further multimodal and prospective studies on hypo- and hyperkinetic movement disorders and sensorimotor/psychomotor functioning in SZ and other psychotic disorders. (C) 2020 Elsevier B.V. and ECNP. All rights reserved.

Objective: Bipolar disorder and unipolar depressive disorder are complex phenotypes. There appear to be phenotypical, mechanistic, and therapeutic differences between bipolar depression (BD) and unipolar depression (UD). There is a need for understanding the underlying biological variation between these clinical entities. The role of oxidative processes underlying bipolar disorder and depression has been demonstrated. Thiol-disulfide homeostasis (TDH) is a recent oxidative stress marker. In this study, we aimed to inspect patients with bipolar depression and unipolar depression in terms of thiol-disulfide balance and to compare them with healthy controls.Methods: Patients admitted to the outpatient clinic of Ankara Numune Training and Research Hospital and diagnosed either as a depressive episode with bipolar disorder (n = 37) or unipolar depression (n = 24) according to DSM-5 criteria, along with healthy controls (HC) (n = 50), were included in the study. Native thiol, total thiol, and disulfide levels were compared across the groups.Results: In comparison to HC, both BD and UD groups had higher disulfide levels, disulfide/native thiol ratio, and disulfide/total thiol ratio. No significant differences between BD and UD were detected in terms of disulfide level, disulfide/native thiol ratio, and disulfide/total thiol ratio.Conclusion: Increased levels of disulfide, native thiol, and disulfide/total thiol ratios compared to healthy controls in both UD and BD groups may be indicative of the presence of oxidative damage in these two clinical conditions. To clarify the role of oxidative stress in the pathophysiology of depressive disorders and investigate TDH, longitudinal studies in patients with medication-free UD and BD are required.

Objectives We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes.Methods A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group.Results Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years).Conclusions There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population.

The efficacy of antidepressants in major depressive disorder has been continually questioned, mainly on the basis of studies using the sum-score of the Hamilton Depression Rating Scale as a primary outcome parameter. On this measure antidepressants show a standardised mean difference of around 0.3, which some authors suggested is below the cut-off for clinical significance. Prompted by a recent review that, using this argument, concluded antidepressants should not be used for adults with major depressive disorder, we (a) review the evidence in support of the cut-off for clinical significance espoused in that article (a Hamilton Depression Rating Scale standardised mean difference of 0.875); (b) discuss the limitations of average Hamilton Depression Rating Scale sum-score differences between groups as measure of clinical significance; (c) explore alternative measures of clinical importance; and (d) suggest future directions to help overcome disagreements on how to define clinical significance. We conclude that (a) the proposed Hamilton Depression Rating Scale cut-off of 0.875 has no scientific basis and is likely misleading; (b) there is no agreed upon way of delineating clinically significant from clinically insignificant; (c) evidence suggests the Hamilton Depression Rating Scale sum-score underestimates antidepressant efficacy; and (d) future clinical trials should consider including measures directly reflective of functioning and wellbeing, in addition to measures focused on depression psychopathology.

Background Cognitive impairment is a frequent nonmotor symptom of Parkinson's disease. Depending on severity, patients are considered to have mild cognitive impairment or dementia. However, among the cognitively intact patients, some may have deficits in a less severe range. The early detection of such subtle symptoms may be important for the initiation of care strategies. Objective To identify imaging markers of early cognitive symptoms, potentially before usual signs, such as atrophy, become manifest. Methods A total of 102 patients with Parkinson's disease and 17 age-matched cognitively intact healthy controls underwent extensive neuropsychological assessment and T1-weighted magnetic resonance imaging. Parkinson's disease patients were separated into 3 groups according to their cognitive status: intact, with slight slowing, and with mild deficits in executive functions. Texture features as measured by first-order and second-order statistics were computed in the following 6 brain regions: the hippocampus, thalamus, amygdala, putamen, caudate nucleus, and pallidum. They were tested between the groups, and their correlation with cognition was examined. Volumetric measurements were made for comparison. Results Texture analysis showed significant between-group differences for 2 features-skewness and entropy in the hippocampus, the thalamus, and the amygdala-and the volume analysis revealed no between-group difference. These features were significantly correlated with cognitive performance. Conclusion These results support the assumption that signal alterations associated with Parkinson's disease-related cognitive decline can be captured very early by texture analysis. As these changes appear to reflect clinical phenomena, texture analysis may be a promising marker for helping cognitive phenotyping in Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.

Cognitive impairment is common in Parkinson's disease (PD), yet with large heterogeneity in the range and course of deficits. In a cross-sectional study, 124 PD patients underwent extensive clinical and neuropsychological assessment as well as a 3T MRI scan of the brain. Our aim was to identify differences in grey matter volume and thickness, as well as cortical folding, across different cognitive profiles as defined through a data-driven exploratory cluster analysis of neuropsychological data. The identified cognitive groups ranged from cognitively intact patients to patients with severe deficits in all cognitive domains, whilst showing comparable levels of motor disability and disease duration. Each group was compared to the cognitively intact PD group using voxel- and vertex-based morphometry. Results revealed widespread age-related grey matter abnormalities associated with progressive worsening of cognitive functions in mild PD. When adjusted for age, significant differences were only seen between cognitively intact and severely affected PD patients and these were restricted to the right posterior cingulate and the right precuneus. Reduced cortical thickness was seen in the right inferior temporal gyrus and reduced folding in the right temporal region. As these differences were not associated with age, we assume that they are associated with underlying pathology of the cognitive decline. Given the limited involvement of grey matter differences, and the absence of differences in vascular changes across the groups, we hypothesize a more important role for white matter tract changes in cognitive decline in PD. (C) 2019 Elsevier Ltd. All rights reserved.

Objectives To explore the prevalence of dysphagia and fear of choking in patients with Huntington’s disease (HD) as well as preventive measures, both those applied and those not included in managing dysphagia. Also, to investigate related problems encountered by their formal and informal caregivers. Design A multi-center observational cross-sectional study Setting and Participants 158 HD patients, recruited from six Dutch nursing homes specialized in HD, and their formal and informal caregivers Measurements Patients were assessed by means of questionnaires enquiring about dysphagia, fear of choking and measures to manage dysphagia. Also, questionnaires were administered about awareness of dysphagia symptoms, cognition and anxiety. Because we expected individuals with greater care dependency to have a higher severity of dysphagia, we distinguished between a care-independent and a care-dependent group of HD patients. Results In the total group, 90.5% of HD patients had one or more dysphagia symptoms. The prevalence of FoC in HD patients and the formal and informal caregivers’ fears about choking in HD patients was 45.7%, 19.0% and 59.5%, respectively, for care-independent patients and 58.7%, 50.1% and 77.5% for care-dependent patients. The score on the Huntington’s Disease Dysphagia Scale was a predictor for fear of FoC in care-independent patients. Speech-language therapy, supervision during eating and drinking and adaptation of food and drink consistency were the most frequently applied measures to manage dysphagia, a combination was used in most HD patients. Conclusions In HD patients, the prevalence of dysphagia is high and fear of choking is common among both patients and caregivers. A more severe degree of dysphagia is a predictor of FoC in care-independent HD patients. A combination of measures was used to manage dysphagia in most HD patients.

The role of astrogliosis in the pathology of brain aging and neurodegenerative diseases has recently drawn great attention. Imidazoline-2 binding sites represent a possible target to map the distribution of reactive astrocytes. In this study, we use 11C-BU99008, an imidazoline-2 binding sites-specific PET radioligand, to image reactive astrocytes in vivo in healthy controls and patients with established Parkinson’s disease dementia. Eighteen healthy controls (age: 45–78 years) and six patients with Parkinson’s disease dementia (age: 64–77 years) had one 11C-BU99008 PET-CT scan with arterial input function. All subjects underwent one 3 T MRI brain scan to facilitate the analysis of the PET data and to capture individual cerebral atrophy. Regional 11C-BU99008 volumes of distribution were calculated for each subject by the two-tissue compartmental modelling. Positive correlations between 11C-BU99008 volumes of distribution values and age were found for all tested regions across the brain within healthy controls (P

Contains fulltext : 217549.pdf (Publisher’s version ) (Closed access) Objectives: To study the effects of discontinuation of long-term methylphenidate use on secondary outcome measures of strengths and difficulties, quality of life (QoL), and parenting stress. Methods: Ninety-four children and adolescents aged 8 to 18 years who had used methylphenidate for over 2 years were randomly assigned to double-blind continuation of treatment for 7 weeks (36 or 54 mg extended release methylphenidate) or to gradual withdrawal over 3 to 4 weeks placebo. We used mixed models for repeated measures to investigate effects on parent, teacher, and child ratings of hyperactivity/inattention and comorbid symptoms with the Strengths and Difficulties Questionnaire (SDQ), investigator- and teacher-rated oppositional symptoms (Conners Teacher Rating Scale-Revised: short form [CTRS-R:S]), and parent-rated aggression with the Retrospective Modified Overt Aggression Scale. QoL was assessed with the Revised Questionnaire for Children and Adolescents to record health-related quality of life and parenting stress with the Nijmegen Parental Stress Index. Results: Hyperactivity/inattention scores from the parent- and teacher-rated SDQ (difference in mean change over time of respectively: -1.1 [95% confidence interval, CI, -2.0 to -0.3]; p = 0.01; -2.9 [95% CI -2.9 to -0.7; p = 0.01]) and oppositional scores of the teacher-rated CTRS-R:S (difference in mean change -1.9 95% CI [-3.1 to -0.6; p

Dystonia is a chronic movement disorder that is associated with a reduction in health-related quality of life (HR-QoL) and restriction of activities of daily living. Botulinum neurotoxin (BT) improves disease-specific HR-QoL by reducing abnormal movements, postures, and pain. We examined the burden of the corresponding primary caregiver as a potential important factor for disease management and HR-QoL of dystonia patients under treatment with BT. 114 patients with focal, segmental, or generalized dystonia were recruited, together with 93 corresponding caregivers, whose burden was investigated using the Caregiver Burden Inventory. In addition, all participants were assessed for cognitive impairment, depression, anxiety, alexithymia, and HR-QoL. Only a small proportion of caregivers suffered from caregiver burden. Despite BT therapy, patients’ HR-QoL was decreased compared to the age-matched general German population. Psychological symptoms, notably anxiety, and depression correlated significantly with reduced HR-QoL. Our data imply that caregiver burden emerged to be an issue in subgroups of dystonia patients. Furthermore, HR-QoL of dystonia patients is reduced even under optimized BT treatment in a specialized center. Electronic supplementary material The online version of this article (10.1007/s00702-019-02109-6) contains supplementary material, which is available to authorized users.

BACKGROUND: Patients with dyskinetic cerebral palsy are often severely impaired with limited treatment options. The effects of deep brain stimulation (DBS) are less pronounced than those in inherited dystonia but can be associated with favorable quality of life outcomes even in patients without changes in dystonia severity. OBJECTIVE: The aim is to assess DBS effects in pediatric patients with pharmacorefractory dyskinetic cerebral palsy with focus on quality of life. METHODS: The method used is a prospective, single-arm, multicenter study. The primary endpoint is improvement in quality of life (CPCHILD [Caregiver Priorities & Child Health Index of Life with Disabilities]) from baseline to 12 months under therapeutic stimulation. The main key secondary outcomes are changes in Burke-Fahn-Marsden Dystonia Rating Scale, Dyskinesia Impairment Scale, Gross Motor Function Measure-66, Canadian Occupational Performance Measure (COPM), and Short-Form (SF)-36. After 12 months, patients were randomly assigned to a blinded crossover to receive active or sham stimulation for 24 hours each. Severity of dystonia and chorea were blindly rated. Safety was assessed throughout. The trial was registered at ClinicalTrials.gov, number NCT02097693. RESULTS: Sixteen patients (age: 13.4 ± 2.9 years) were recruited by seven clinical sites. Primary outcome at 12-month follow-up is as follows: mean CPCHILD increased by 4.2 ± 10.4 points (95% CI [confidence interval] -1.3 to 9.7; P = 0.125); among secondary outcomes: improvement in COPM performance measure of 1.1 ± 1.5 points (95% CI 0.2 to 1.9; P = 0.02) and in the SF-36 physical health component by 5.1 ± 6.2 points (95% CI 0.7 to 9.6; P = 0.028). Otherwise, there are no significant changes. CONCLUSION: Evidence to recommend DBS as routine treatment to improve quality of life in pediatric patients with dyskinetic cerebral palsy is not yet sufficient. Extended follow-up in larger cohorts will determine the impact of DBS further to guide treatment decisions in these often severely disabled patients. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. ispartof: MOVEMENT DISORDERS vol:37 issue:4 pages:799-811 ispartof: location:United States status: published

OBJECTIVE: To identify markers of Parkinson's disease (PD) related anxiety, using high density electroencephalography (hd-EEG).METHODS: 108 patients participated in the study. They were divided into two groups: with and without clinically relevant anxiety, according to their score on the Parkinson Anxiety Scale. Resting-state hd-EEG was recorded. Spectral and functional connectivity characteristics were compared between the two groups.RESULTS: Thirty-three patients (31%) had significant anxiety symptoms. In the spectral analysis, relative power in the alpha1 frequency band in the right prefrontal cortex was lower in patients with anxiety than without. Functional connectivity analysis showed a stronger connectivity between the left insula and several regions of the right prefrontal cortex in patients with anxiety than in those without.CONCLUSION: This study shows the pivotal role of the insula and frontal cortex in the pathophysiology of anxiety in PD and extends the results of previous studies using magnetic resonance imaging or positron emission tomography imaging.

Emotion differentiation (ED), the extent to which same-valenced emotions are experienced as distinct, is considered a valuable ability in various contexts owing to the essential affect-related information it provides. This information can help individuals understand and regulate their emotional and motivational states. In this study, we sought to examine the extent to which ED can be beneficial in psychotherapy context and specifically for predicting treatment response. Thirty-two prospective patients with mood and anxiety disorders completed four daily assessments of negative and positive emotions for 30 days before receiving cognitive-behavioral treatment. Depression, stress, and anxiety symptoms severity were assessed pre- and post-treatment using self-reports and clinical interviews. We conducted a series of hierarchical regression models in which symptoms change scores were predicted by ED while adjusting for the mean and variability. We found that negative ED was associated with greater self-reported treatment response (except for anxiety) when negative emotional variability (EV) was included in the models. Probing negative ED and EV's interactive effects suggested that negative ED was associated with greater treatment response (except for anxiety) for individuals with lower EV levels. Results were obtained while controlling for mean negative affect. Our findings suggest that negative ED can benefit psychotherapy patients whose negative emotions are relatively less variable. We discuss the meaning of suppression and interactive effects between affect dynamics and consider possible clinical implications. ispartof: FRONTIERS IN PSYCHOLOGY vol:12 ispartof: location:Switzerland status: published

Background Visual hallucinations are common in patients with Parkinson's disease and represent probably the major independent predictor for cognitive deterioration and nursing home placement. Objective To investigate if treatment of minor visual hallucinations in Parkinson's disease with rivastigmine delays the progression to psychosis. Methods A multicenter, randomized, double‐blind, placebo‐controlled trial was conducted which aimed to recruit 168 patients with Parkinson's disease reporting minor visual hallucinations 4 weeks before it. Important exclusion criteria were Parkinson's disease dementia, current delirium, and treatment with antipsychotics or drugs that have significant anti‐cholinergic side effects. Subjects were randomized to rivastigmine capsules, 3–6 mg twice a day, or placebo for 24 months. The primary outcome was the time to Parkinson's disease psychosis, which was defined as the need to start with antipsychotics. Results The trial was stopped prematurely because of slow recruitment. Ninety‐one patients were randomized: 46 patients were assigned to rivastigmine and 45 patients to placebo. No effect of rivastigmine could be demonstrated on the transition time to psychosis or dementia during the 24‐month follow‐up period. After 6 months of study treatment, cognition, mood, motor performance, and non‐motor performance did not differ significantly between the rivastigmine‐group and the placebo‐group. Conclusions Because the study was terminated early, it was insufficiently powered to properly evaluate the primary outcome. The limited data of the study favor a wait and see approach instead of early treatment with rivastigmine in PD patients with minor VH., A randomized controlled trial was conducted to investigate if treatment of minor visual hallucinations in Parkinson's disease with rivastigmine delays the progression to psychosis. The limited data of our study favor a wait and see approach instead of early treatment.

Visual deficits are core deficits of schizophrenia. Classically, deficits are determined with demanding psychophysical tasks requiring fine-grained spatial or temporal resolution. Less is known about holistic processing. Here, we employed the Leuven Embedded Figures Test (L-EFT) measuring classic aspects of Gestalt processing. A target shape is embedded in a context and observers have to detect as quickly as possible in which display the target is embedded. Targets vary in closure, symmetry, complexity, and good continuation. In all conditions, schizophrenia patients had longer RTs compared to controls and depressive patients and to a lesser extent compared to their siblings. There was no interaction suggesting that, once the main deficit of schizophrenia patients is discarded, there are no further deficits in Gestalt perception between the groups. This result is in line with a growing line of research showing that when schizophrenia patients are given sufficient time to accomplish the task, they perform as well as controls. ispartof: SCHIZOPHRENIA RESEARCH-COGNITION vol:28 ispartof: location:United States status: published

Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness.Methods: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R2) at the optimal p-value threshold is reported.Results: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R2 = 8.18%, p = .0013), Belgium (R2 = 6.83%, p = .016), and the Netherlands (R2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R2 = 4.42%, p = .0024) and unipolar MDE only (R2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold.Conclusions: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry.

Schizophrenia spectrum disorders (SSDs) are complex syndromes involving psychopathological, cognitive, and also motor symptoms as core features. A better understanding of how these symptoms mutually impact each other could translate into diagnostic, prognostic, and, eventually, treatment advancements. The present study aimed to: (1) estimate a network model of psychopathological, cognitive, and motor symptoms in SSD; (2) detect communities and explore the connectivity and relative importance of variables within the network; and (3) explore differences in subsample networks according to remission status. A sample of 1007 patients from a multisite cohort study was included in the analysis. We estimated a network of 43 nodes, including all the items from the Positive and Negative Syndrome Scale, a cognitive assessment battery and clinical ratings of extrapyramidal symptoms. Methodologies specific to network analysis were employed to address the study’s aims. The estimated network for the total sample was densely interconnected and organized into 7 communities. Nodes related to insight, abstraction capacity, attention, and suspiciousness were the main bridges between network communities. The estimated network for the subgroup of patients in remission showed a sparser density and a different structure compared to the network of nonremitted patients. In conclusion, the present study conveys a detailed characterization of the interrelations between a set of core clinical elements of SSD. These results provide potential novel clues for clinical assessment and intervention.

Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case–control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2%; OR = 1.50; 95% CI: 0.58–3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p p p p p

OBJECTIVES: The examination of retinal microvascular abnormalities through fundus photography is currently the best available non-invasive technique for assessment of cerebral vascular status. Several studies in the last decade have reported higher incidences of adverse cerebrovascular events in Schizophrenia (SCZ) and bipolar disorder (BD). However, retinal microvasculature abnormalities in SCZ and BD have remained under-explored, and no study has compared this aspect of SCZ and BD till date.METHODS: Retinal Images of 100 SCZ patients, BD patients, and healthy volunteers each were acquired by trained individuals using a non-mydriatic camera with a 40-degree field of view. The retinal images were quantified using a valid semi-automated method. The average of left and right eye diameters of the venules and arterioles passing through the extended zone between 0.5 and 2 disc diameters from the optic disc were calculated.RESULTS: The groups differed significantly with respect to average diameters of both retinal venules (P < 0.001) and retinal arterioles (P < 0.001), after controlling for age and sex. Both SCZ and BD patients had significantly narrower arterioles and wider venules compared to HV. There were also significant differences between SCZ and BD patients; patients with BD had narrower arterioles and wider venules.CONCLUSION: Considering the affordability and easy accessibility of the investigative procedure, retinal microvascular examination could serve as a potential screening tool to identify individuals at risk for adverse cerebrovascular events. The findings of the current study also provide a strong rationale for further systematic examination of retinal vascular abnormalities in SCZ and BD.

Pleasantness is generally overlooked when investigating tactile functions. Addition of a pleasant stimulus could allow for a more complete characterisation of somatosensory function. The aims of this review were to systematically assess the methodologies used to elicit a pleasant sensation, measured via psychophysical techniques, and to perform a meta-analysis to measure the effect of brush stroking velocity on touch pleasantness. Eighteen studies were included in the systematic review, with five studies included in the meta-analysis. The review found that factors such as texture, velocity, force, and the duration of continuous stroking influence tactile evoked pleasantness. Specifically, using a soft material and stroking at a velocity of 3 cm/s with light force is generally considered as particularly pleasant. The meta-analysis showed that a brush stroking velocity of 30 cm/s was rated as less pleasant than 3 cm/s, on the forearm. The present study collates the factors that are most likely to provide a stimulus to elicit a pleasant sensation. The results should be important for studies requiring a well-defined pleasant stimulus including neurosensory assessment protocols, allowing for a more complete multimodality assessment of somatosensory function.