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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).

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.

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.

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.

Background: A previous study reported a dramatic mismatch in objectively detected and self-reported tremor duration in patients with functional tremor. As these findings have an important and widespread impact in both clinical care and research, we conducted a validation study with a longer study duration and a larger sample of patients.Methods: Fourteen patients with functional tremor and 19 with organic tremor completed a 30 day study period. Objective tremor duration was recorded using a wrist-worn accelerometer. Simultaneously, participants completed a web-based diary five times a day, each time rating their symptom burden since the previous diary entry.Results: Patients with functional tremor had shorter objective tremor duration compared to patients with organic tremor (21.6% vs 30.7%, P = 0.034). A post-hoc analysis revealed the difference in objective duration was mainly due to patients with essential tremor (37.2%). Subjective symptom burden was not significantly different between functional and organic tremors (38.7 vs 28.7 on a 0-100 VAS scale, P = 0.138). Finally, a mixed model analysis did not reveal significant differences in the association between subjective and objective tremor symptoms (P = 0.168).Conclusions: patients with functional tremor do have an objectively detectable, persistent tremor during daily life activities. Furthermore, they have a similar symptom burden and a similar association between subjective and objective tremor symptoms as patients with organic tremor.

Little is known about the co-prevalence of obsessive compulsive symptoms (OCS) and motor symptoms in patients with psychotic disorders. Cross-sectional associations between OCS and motor symptoms were assessed at baseline and at 3 years follow-up in patients (n = 726) with psychotic disorders and in their unaffected siblings (n = 761) from the Dutch Genetic Risk and Outcome of Psychosis (GROUP) study. Furthermore, longitudinal associations between changes in OCS and motor symptoms were evaluated. At baseline, OCS was not associated with any motor symptom (akathisia, dyskinesia, parkinsonism or dystonia) in patients. At follow-up, patients with OCS reported significantly more akathisia. Dividing the patients into four groups-no OCS, OCS remission with OCS only at baseline, OCS de novo with OCS only at follow-up and a persistent OCS group-revealed that the OCS de novo group already reported more akathisia at baseline compared to the no-OCS group. At follow-up, both the OCS de novo and the persistent OCS group reported more akathisia. These results remained significant after correcting for relevant confounders clozapine, GAF score, PANSS-negative score and IQ. Motor symptoms at baseline were significantly associated with OCS at follow-up, but not the other way around. In siblings, OCS at baseline was associated with akathisia, but this association was lost at follow-up. Results suggest that motor symptoms might precede co-occurring OCS in patients with psychotic disorders. However, no inference can be made about causality, and further prospective research is needed to investigate this assumption. ispartof: EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE vol:269 issue:2 pages:257-268 ispartof: location:Germany status: published

OBJECTIVE: The Self-Awareness in Daily Life-3 Scale (SADL-3) was designed to assess self-awareness in the chronic phase after acquired brain injury (ABI). The main objective was to evaluate its feasibility and usability for clinical practice, reliability and validity.METHODS: Participants were 89 patients with ABI. SADL-3 core distributions, floor and ceiling effects and percentage of missing items were used. Ratings made by two staff members and ratings at two time points were compared. SADL-3 ratings were compared with Awareness Questionnaire (AQ) ratings, Patient Competency Rating Scale (PCRS) ratings, and ratings made on the Clinician's Rating Scale for evaluating Impaired Self-Awareness and Denial of Disability (CRS-ISA-DD). Staff members completed a questionnaire concerning the usability of the SADL-3.RESULTS: No floor or ceiling effects were present. Results show sufficient inter-rater reliability (ICC > .40), acceptable test-retest reliability (ρs > .75) and sufficient convergent validity (ρs > .30). The median administration time was 15 minutes (SD = 21.2). Most staff members rated the SADL-3 as fairly easy to very easy to complete.CONCLUSIONS: The SADL-3 is a brief scale with sufficient psychometric properties. Teams can use it in clinical practice to identify patients' self-awareness in the chronic phase after ABI.

What drives the large differences across patients in terms of treatment efficacy of major depressive disorder (MDD) is unclear. A network approach to psychopathology may help to reveal underlying mechanisms determining patients' capacity for recovery. We used daily diary MDD symptom data and six-month follow-up data on depression to examine how dynamic associations between symptoms relate to the future course of MDD. Daily experiences of depressive symptoms of 69 participants were assessed by means of the SCL-90-R depression subscale, three days a week for a period of six weeks, as part of a larger intervention study. Multilevel vector autoregressive modelling was used to estimate networks of dynamic symptom connections. Long-term outcome was determined by the percentage change in Hamilton Depression Rating Scale (HDRS) score between pre-intervention and six-month follow-up. For patients with more persisting symptoms, the symptom 'feeling everything is an effort' most strongly predicted other symptoms. The networks of the two groups did not significantly differ in overall connectivity. Findings suggest that future research should not solely focus on the presence or intensity of individual symptoms when predicting long-term outcomes, but should also examine the role of a specific symptom in the larger network of dynamic symptom-to-symptom interactions.

Objective: The identification of predictors of psychosis remission could guide early clinical decision-making for treatment of first-episode schizophrenia (FES).Methods: We analyzed two non-independent subsamples of patients with FES ages 18-40 years from the OPTiMiSE study dataset to investigate the demographic and clinical factors that might help to differentiate "late" re-mitters (i.e., not in remission at week 2 or 4, but achieving remission within a 10-week follow-up period) from non-remitters within the same period.Results: Subsample 1 included 216 individuals (55 females, mean age 25.9 years) treated with amisulpride in an open-label design who were not in remission at week 2. Early symptomatic response between baseline and week 2 (odds ratio (OR)- 4.186, 95% confidence interval (CI)- 2.082-8.416, p < 0.001) and older age (OR- 1.081, 95% = CI 1.026-1.138, p- 0.003) were the only variables significantly associated with a higher probability of psychosis remission at week 4. Subsample 2 was composed of the 72 participants (19 females, mean age 25.1 years) who were not in remission at week 4 and completed a 6-week double-blind randomized trial comparing continuation of amisulpride with switch to olanzapine. Depression at baseline (as measured with the Calgary Depression Scale for Schizophrenia) was significantly associated with a nearly 3-fold lower likelihood of psychosis remission during the 10-week follow-up (hazard ratio = 2.865, 95% CI = 1.187-6.916, p = 0.019).Conclusion: Our results reinforce the importance of assessing depressive symptoms in people with FES and support the relevance of an early response (as early as 2 weeks) as a predictor of clinical outcome in this population. (C) 2021 Elsevier B.V. All rights reserved.

Background Standard depression rating scales like the Hamilton Depression Rating Scale and the Montgomery–Åsberg Depression Rating Scale were developed more than 40 years ago. They are mandatory in clinical trials but are for a variety of reasons seldom used in clinical practice. Moreover, most clinicians are less familiar with more recent trends or with some dilemmas in assessment tools for major depression. Methods Narrative review. Results Asssessment tools can be observer-rating or self-rating scales, disease-specific or non–disease-specific scales, subjective scales or objective lab assessments, standard questionnaires or experience sampling methods. An overarching question is to what degree current assessment methods really address the individual patient’s needs and treatment expectations. Conclusions The present paper aims to offer a framework for understanding the current trends in assessment tools that can orientate and guide the clinician.

BACKGROUND: There are no reliable and validated objective biomarkers for the assessment of depression severity. We aimed to investigate the association between depression severity and timing-related speech features using speech recognition technology. METHOD: Patients with major depressive disorder (MDD), those with bipolar disorder (BP), and healthy controls (HC) were asked to engage in a non-structured interview with research psychologists. Using automated speech recognition technology, we measured three timing-related speech features: speech rate, pause time, and response time. The severity of depression was assessed using the Hamilton Depression Rating Scale 17-item version (HAMD-17). We conducted the current study to answer the following questions: 1) Are there differences in speech features among MDD, BP, and HC? 2) Do speech features correlate with depression severity? 3) Do changes in speech features correlate with within-subject changes in depression severity? RESULTS: We collected 1058 data sets from 241 individuals for the study (97 MDD, 68 BP, and 76 HC). There were significant differences in speech features among groups; depressed patients showed slower speech rate, longer pause time, and longer response time than HC. All timing-related speech features showed significant associations with HAMD-17 total scores. Longitudinal changes in speech rate correlated with changes in HAMD-17 total scores. CONCLUSIONS: Depressed individuals showed longer response time, longer pause time, and slower speech rate than healthy individuals, all of which were suggestive of psychomotor retardation. Our study suggests that speech features could be used as objective biomarkers for the assessment of depression severity. ispartof: PLOS ONE vol:15 issue:9 ispartof: location:United States status: published

Background: Antipsychotics are key for the treatment of psychotic and several non-psychotic disorders. Unfortunately, antipsychotic medications are associated with side effects, which may reduce quality of life and treatment adherence. Therefore, regular screening of antipsychotic side effects is essential. The Glasgow Antipsychotic Side-effect Scale is a patient self-report scale developed for this purpose. However, the Glasgow Antipsychotic Side-effect Scale has only been validated against another self-report side effect measure, which is suboptimal. Objective: We aimed to validate the Glasgow Antipsychotic Side-effect Scale using the clinician-rated Udvalg for Kliniske Undersøgelser side-effect rating scale as the gold standard reference. Results: 81 antipsychotic-treated outpatients with schizophrenia-spectrum disorders (age = 42±13 years; males = 43%, schizophrenia = 77%, illness duration: median = 11 years) completed the Glasgow Antipsychotic Side-effect Scale and were subsequently scored on the Udvalg for Kliniske Undersøgelser by trained raters. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for paired Glasgow Antipsychotic Side-effect Scale and Udvalg for Kliniske Undersøgelser items. Sensitivity of Glasgow Antipsychotic Side-effect Scale items ranged from 33–96%, with 19 (86%) having >75% sensitivity. Lowest sensitivity emerged for “nocturnal enuresis” (33%), “galactorrhea” (50%) and “hyperkinesia” 14–99%, with 14 items (64%) having >75% specificity, being lowest for “asthenia” (14%), “polyuria/polydipsia” (35%), “sedation” (41%), “akathisia” (53%), “dystonia” (65%), “hyperkinesia” (68%), “hypokinesia” (70%) and “accommodation” (70%). Positive predictive value ranged from 7–85%, with six items (27%) having a positive predictive value >75%. Negative predictive value ranged from 40–98%, with 21 items (95%) having a negative predictive value >75%. The mean time to complete the Glasgow Antipsychotic Side-effect Scale was 4±2 minutes. Conclusion: The Glasgow Antipsychotic Side-effect Scale demonstrated satisfactory validity as a self-rated tool for antipsychotic side effects and may aid measurement-based care and decision-making.

There is an accumulation in studies which strive to reveal zonulin's potential role in mental disorders. To date, one cross-sectional recent study examined zonulin in patients with bipolar disorders (BDs); however, its role still remains vague due to high fluctuation. Our aims are to determine plasma zonulin levels in exacerbation and treatment response periods, and to examine the associations between zonulin and symptom severity in BD. 30 patients with BD type I and 29 healthy controls participated in the current study. Socio-demographic form, Young Mania Rating Scale (YMRS), and Hamilton Depression Rating Scale (HAM-D) were administered. Enzyme-linked immune assay (ELISA) method was used to measure the plasma zonulin levels of the participants. The groups did not differ in plasma zonulin-level comparisons. Plasma zonulin did not alter between the exacerbation and treatment response periods of the patients. Besides, no associations were found between plasma zonulin-level and disease symptoms. Intestinal barrier integrity was not found to be altered among patients with BD type I. The lack of alterations in plasma zonulin level between different periods may be attributable to several factors. One possible factor might be the ELISA method which can detect other proteins (e.g., properdin) rather than zonulin. Therefore, it might fail to indicate direct observation of intestinal permeability. However, future study designs with more accurate estimation of zonulin in a larger sample may provide a different perspective on intestinal permeability's possible role in BD etiology. Celal Bayar Üniversitesi (2018-225)

Loss of cognitive ability is commonly associated with dementia, a broad category of progressive brain diseases.~However, major depressive disorder may also cause temporary deterioration of one&rsquo, s cognition known as pseudodementia.~Differentiating a true dementia and pseudodementia is still difficult even for an experienced clinician and extensive and careful examinations must be performed. Although mental disorders such as depression and dementia have been studied, there is still no solution for shorter and undemanding pseudodementia screening. This study inspects the distribution and statistical characteristics from both dementia patient and depression patient, and compared them. It is found that some acoustic features were shared in both dementia and depression, albeit their correlation was reversed. Statistical significance was also found when comparing the features. Additionally, the possibility of utilizing machine learning for automatic pseudodementia screening was explored. The machine learning part includes feature selection using LASSO algorithm and support vector machine (SVM) with linear kernel as the predictive model with age-matched symptomatic depression patient and dementia patient as the database. High accuracy, sensitivity, and specificity was obtained in both training session and testing session. The resulting model was also tested against other datasets that were not included and still performs considerably well. These results imply that dementia and depression might be both detected and differentiated based on acoustic features alone. Automated screening is also possible based on the high accuracy of machine learning results.

Emerging evidence indicates abnormal retinal micro-vasculature in schizophrenia (SCZ) and bipolar disorder (BD) and its relation to cognitive functions. However, the association of these abnormalities with the cognitive deficits in these disorders has not been examined till date. Hence, we explored this aspect in patients with SCZ, BD, and healthy volunteers (HV). We examined 34 with SCZ, 39 with BD, and 45 HV. Retinal images were acquired using nonmydriatic fundus camera. The retinal images were analyzed, and average diameters of retinal arterioles and venules were calculated. Working memory was assessed using computerized one-back test from Cogstate® battery. There was significant difference between groups in retinal venules and arterioles caliber (p < 0.001). Both SCZ and BD patients had wider venules and narrower arterioles. They had significantly lower working memory accuracy (p = 0.008) and higher log mean speed (p < 0.001). There was significant positive correlation between one-back test accuracy and retinal arteriolar caliber (r = 0.22; p = 0.01) and between log mean speed score and retinal venular caliber (r = 0.20; p = 0.02). Findings suggest association between working memory and retinal vascular caliber, a potential pointer towards understanding the vascular pathology in cognitive deficits in SCZ and BD. Future studies need to examine whether retinal vascular could be a biomarker for SCZ and BD.

BackgroundPatients with epilepsy (PwE) have an increased risk of active and lifetime depression. Two in 10 patients experience depression. Lack of trained psychiatric staff in low- and middle-income countries (LMIC) creates a need for screening tools that enable detection of depression in PwE. We describe the translation, validity and reliability assessment of the Patient Health Questionnaire-9 (PHQ-9) as a screening tool for depression among PwE in Rwanda.MethodPHQ-9 was translated to Kinyarwanda using translation-back translation and validated by a discussion group. For validation, PwE of ≥15 years of age were administered the PHQ-9 and Hamilton Depression Rating Scale (HDRS) by trained psychiatry staff at Visit 1. A random sample of 20% repeated PHQ-9 and HDRS after 14 days to assess temporal stability and intra-rater reliability. Internal structure, reliability and external validity were assessed using confirmatory factor analysis, reliability coefficients and HDRS-correlation, respectively. Maximal Youden's index was considered for cut-offs.ResultsFour hundred and thirty-four PwE, mean age 30.5 years (SD ±13.3), were included of whom 33.6%, 37.9%, 13.4%, and 15.1% had no, mild, moderate and severe depression, respectively. PHQ-9 performed well on a one-factor model (unidimensional model), with factor loadings of 0.63-0.86. Reliability coefficients above 0.80 indicated strong internal consistency. Good temporal stability was observed (0.79 [95% CI: 0.68-0.87]). A strong correlation (R = 0.66, p = 0.01) between PHQ-9 and HDRS summed scores demonstrated robust external validity. The optimal cut-off for the PHQ-9 was similar (≥5) for mild and moderate depression and ≥7 for severe depression.ConclusionPHQ-9 validation in Kinyarwanda creates the capacity to screen PwE in Rwanda at scores of ≥5 for mild or moderate and ≥7 for severe depression. The availability of validated tools for screening and diagnosis for depression is a forward step for holistic care in a resource-limited environment.

Made available in DSpace on 2019-09-12T16:56:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2019 Fundação de Amparo à Pesquisa do Estado de Minas Gerais (Fapemig) Objective To evaluate the epidemiological and microbiological aspects of the potential association between bipolar affective disorder (BAPD) and periodontitis. Methodology The present case-control study comprised 176 individuals with BAPD and 176 controls. All individuals underwent a complete full-mouth periodontal examination and microbiological sampling. Data on bleeding on probing, probing depth, and clinical attachment level in all present teeth were recorded. Quantification of total bacterial load and Aggregatibacter actinomycetemcomitans, Treponema denticola, and Porphyromonas gingivalis counts were performed through qPCR. Data were analyzed using univariate analysis, Spearman correlation and multivariate logistic regression. Results The prevalence of periodontitis was 39.7% among controls and 58.5% among individuals with BAPD (OR = 2.13; 95% CI 1.39-3.27). A. actinomycetemcomitans and P. gingivalis counts were significantly higher in individuals with BPAD and periodontitis. The final multivariate logistic regression revealed that periodontitis was strongly associated with the total bacterial load (OR = 1.91; 95% IC = 1.0-1.99; P < 0.001) and the depressive phase of BPAD (OR = 28.94; 95% IC = 4.44-177.27; P < 0.001). Conclusion BAPD was associated with increased risk for periodontitis. Individuals with BPAD presented higher levels of A. actinomycetemcomitans and P. gingivalis, suggesting that periodontitis could be a co-morbidity frequently found in individuals with BAPD. [Cunha, Fabiano A.; Cota, Luis O. M.; Neves, Fernando S.; Costa, Fernando O.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil [Cortelli, Sheila C.; Miranda, Tais B.; Cortelli, Jose R.] Universidade de Taubaté (Unitau)

Background Anxiety disorders occur in up to 35% of patients with Parkinson's disease (PD) and have a negative effect on motor symptoms and quality of life. To date, no clinical trials specifically targeting anxiety in PD patients have been published. Objective To describe the rationale and methodology of a randomised controlled trial (RCT) that aims to study the clinical effectiveness, alterations in brain circuitry, and cost-effectiveness of cognitive behavioural therapy (CBT) for anxiety in PD. Methods This study is a prospective, two-centre RCT in which sixty PD patients with anxiety will be randomised to CBT treatment and clinical monitoring (intervention group) or to clinical monitoring only (control group). The CBT module used in this study was specifically developed to address symptoms of anxiety in PD patients. Participants will undergo standardised clinical, cognitive and behavioural assessment at baseline and at 2 follow-up measurements, as well as resting-state fMRI and DTI scanning before and after the intervention. The primary outcome measure is changes in severity of anxiety symptoms. Secondary outcome measures involve long-term changes in anxiety symptoms, changes in functional and structural connectivity between limbic and frontal cortices, and cost-effectiveness of the treatment. The study is registered at the ClinicalTrials.gov database under registration number NCT02648737 . Conclusion This study is the first that evaluates both the clinical effectiveness, cost-effectiveness, as well as the biological impact of CBT for anxiety in PD patients that, if proven effective, will hopefully contribute to a better and evidence-based approach for these non-motor symptoms.

BackgroundAlthough the study of the neuroanatomical correlates of generalized anxiety disorder (GAD) is gaining increasing interest, up to now the cortical anatomy of GAD patients has been poorly investigated and still no data on cortical gyrification are available. The aim of the present study is to quantitatively examine the cortical morphology in patients with GAD compared with healthy controls (HC) using magnetic resonance imaging (MRI). To the best of our knowledge, this is the first study analyzing the gyrification patterns in GAD.MethodsA total of 31 GAD patients and 31 HC underwent 3 T structural MRI. For each subject, cortical surface area (CSA), cortical thickness (CT), gray matter volume (GMV), and local gyrification index (LGI) were estimated in 19 regions of interest using the Freesurfer software. These parameters were then compared between the two groups using General Linear Model designs.ResultsCompared with HC, GAD patients showed: (1) reduced CT in right caudal middle frontal gyrus (p < 0.05, Bonferroni corrected), (2) hyper-gyrification in right fusiform, inferior temporal, superior parietal and supramarginal gyri and in left supramarginal and superior frontal gyri (p < 0.05, Bonferroni corrected). No significant alterations in CSA and GMV were observed.ConclusionsOur findings support the hypothesis of a neuroanatomical basis for GAD, highlighting a possible key role of the right hemisphere. The alterations of CT and gyrification in GAD suggest a neurodevelopmental origin of the disorder. Further studies on GAD are needed to understand the evolution of the cerebral morphology with age and during the clinical course of the illness.

Background: Bipolar disorder (BD) and schizophrenia (SCZ), are associated with greater vascular co-morbidities and adverse vascular events. Owing to shared developmental origins and morphology, retinal vasculature is a proxy assessment measure of the cerebral vasculature. Although retinal vascular fractal dimension (Df), a measure of vascular geometry and complexity of branching, has been shown to be directly associated with cerebrovascular pathology, it has not been examined in SCZ and BD. Methods: We studied 277 participants (92 healthy volunteers, 98 SCZ, and 87 BD) from 18 to 50 years of age. Images were acquired by trained personnel using a non-mydriatic fundus camera and the retinal vascular Df was calculated by the box-counting method using an automated algorithm. The average Df across the left and right eyes were calculated. Results: Both SCZ and BD had significantly increased Df compared to HV despite controlling for possible confounding factors. However, there was no significant difference between SCZ and BD. These findings suggest abnormal retinal vascular Df in psychoses. Limitations: The study design was cross-sectional, and patients were on medications. Confound of lifestyle factors such as diet and exercise, if any, was not controlled. Sub-group analysis between BD-I and BD-II was not performed in view of the small sample. Conclusions: Considering the easy accessibility, affordability, and non-invasive nature of the examination, retinal vascular Df could serve as a surrogate marker for cerebral vascular abnormality and could potentially identify BD and SCZ patients at risk of developing adverse vascular events.

Objective: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) are thought to reflect the high, symptomatic extreme of quantitative trait continua. However, extreme deviations in either direction on disorder continua, high and low, may both represent maladaptive behavioral and cognitive outcomes. We aimed to test this hypothesis. Method: In a population sample of 378 children, ADHD and ASD traits were rated by parents on questionnaires that provide resolution at high and low extremes of the ADHD and ASD trait continua. ADHD and ASD traits were related to parent-ratings of internalizing and externalizing behavior problems and tests of cognitive functioning using polynomial regression. Results: The low ends of the ADHD and ASD trait continua were related to fewer behavior problems and better cognitive functioning than symptomatic ends. Conclusion: Studying the correlates of the low continuum ends may deepen our understanding of the mechanisms underlying adaptive behavioral and cognitive outcomes.

Background Drug-related movement disorders (DRMDs) reduce quality of life and contribute to medication noncompliance of patients with psychotic disorders. Little is known about the epidemiology of DRMDs in relatively young patients a few years after onset of psychosis. This is an important period to study, as the impact of the antipsychotic treatment on the long-term potentiation of the neural pathways associated with psychotic disorders and DRMDs is still minimal. This study investigated the prevalence, incidence, persistence, and clinical correlates of DRMDs in patients during their first years after disease onset.Methods The Genetic Risk and Outcome of Psychosis study is a longitudinal study of 1120 relatively young patients with nonaffective psychosis and a mean age and illness duration of 27 and 4 years, respectively. The following drug-related movement disorders were assessed at baseline and at the 3-year follow-up: parkinsonism, akathisia, tardive dyskinesia, and tardive dystonia. We determined prevalence, incidence, and persistence and investigated clinical correlates at and over the baseline and follow-up assessment.Results Patients' mean age and illness duration at baseline were 27.1 and 4.3 years, respectively. In 4 patients, 1 developed a DRMD over the 3-year study period. Prevalence, incidence, and persistence rates were highest for parkinsonism (32%, 21%, and 53%) followed by akathisia (9%, 5%, and 17%) and tardive dyskinesia (4%, 3%, and 20%). Significant associations were found between DRMDs and the patients' age, IQ, and psychopathology.Conclusions The prevalence, persistence, and incidence of DRMDs in this sample were high despite the relatively young age, recent onset of the disorder, and treatment primarily with second-generation antipsychotics. These findings emphasize that screening, diagnosis, and treatment of DRMDs are still important.

BackgroundAlthough repeatedly associated with white matter microstructural alterations, bipolar disorder (BD) has been relatively unexplored using complex network analysis. This method combines structural and diffusion magnetic resonance imaging (MRI) to model the brain as a network and evaluate its topological properties. A group of highly interconnected high-density structures, termed the ‘rich-club’, represents an important network for integration of brain functioning. This study aimed to assess structural and rich-club connectivity properties in BD through graph theory analyses.MethodWe obtained structural and diffusion MRI scans from 42 euthymic patients with BD type I and 43 age- and gender-matched healthy volunteers. Weighted fractional anisotropy connections mapped between cortical and subcortical structures defined the neuroanatomical networks. Next, we examined between-group differences in features of graph properties and sub-networks.ResultsPatients exhibited significantly reduced clustering coefficient and global efficiency, compared with controls globally and regionally in frontal and occipital regions. Additionally, patients displayed weaker sub-network connectivity in distributed regions. Rich-club analysis revealed subtly reduced density in patients, which did not withstand multiple comparison correction. However, hub identification in most participants indicated differentially affected rich-club membership in the BD group, with two hubs absent when compared with controls, namely the superior frontal gyrus and thalamus.ConclusionsThis graph theory analysis presents a thorough investigation of topological features of connectivity in euthymic BD. Abnormalities of global and local measures and network components provide further neuroanatomically specific evidence for distributed dysconnectivity as a trait feature of BD.

Background: North Sea Progressive Myoclonus Epilepsy is a rare and severe disorder caused by mutations in the GOSR2 gene. It is clinically characterized by progressive myoclonus, seizures, early-onset ataxia and areflexia. As in other progressive myoclonus epilepsies, the efficacy of antiepileptic drugs is disappointingly limited in North Sea Progressive Myoclonus Epilepsy. The ketogenic diet and the less restrictive modified Atkins diet have been proven to be effective in other drug-resistant epilepsy syndromes, including those with myoclonic seizures. Our aim was to evaluate the efficacy of the modified Atkins diet in patients with North Sea Progressive Myoclonus Epilepsy.Results: Four North Sea Progressive Myoclonus Epilepsy patients (aged 7-20 years) participated in an observational, prospective, open-label study on the efficacy of the modified Atkins diet. Several clinical parameters were assessed at baseline and again after participants had been on the diet for 3 months. The primary outcome measure was healthrelated quality of life, with seizure frequency and blinded rated myoclonus severity as secondary outcome measures. Ketosis was achieved within 2 weeks and all patients completed the 3 months on the modified Atkins diet. The diet was well tolerated by all four patients. Health-related quality of life improved considerably in one patient and showed sustained improvement during long-term follow-up, despite the progressive nature of the disorder. Health-related quality of life remained broadly unchanged in the other three patients and they did not continue the diet. Seizure frequency remained stable and blinded rating of their myoclonus showed improvement, albeit modest, in all patients.Conclusions: This observational, prospective study shows that some North Sea Progressive Myoclonus Epilepsy patients may benefit from the modified Atkins diet with sustained health-related quality of life improvement. Not all our patients continued on the diet, but nonetheless we show that the modified Atkins diet might be considered as a possible treatment in this devastating disorder.

To examine changes in motor subtype profile in individuals with delirium. Observational, longitudinal study; substudy of a multicenter, randomized controlled trial. Departments of surgery and orthopedics, Academic Medical Center and Tergooi Hospital, the Netherlands. Elderly adults acutely admitted for hip fracture surgery who developed delirium according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, for 2 days or longer (n = 76, aged 86.4 ± 6.1, 68.4% female). Delirium Motor Subtype Scale (DMSS), Delirium Rating Scale R98 (DRS-R98), comorbidity, and function. Median delirium duration was 3 days (interquartile range 2.0 days). At first assessment, the hyperactive motor subtype was most common (44.7%), followed by hypoactive motor subtype (28.9%), mixed motor subtype (19.7%), and no motor subtype (6.6%). Participants with no motor subtype had lower DRS-R98 scores than those with the other subtypes (P < .001). The DMSS-defined motor subtype of 47 (61.8%) participants changed over time. Katz Index of Activities of Daily Living, Charlson Comorbidity Index, cognitive impairment, age, sex, and delirium duration or severity were not associated with change in motor subtype. Motor subtype profile was variable in the majority of participants, although changes that occurred were often related to changes from or to no motor subtype, suggesting evolving or resolving delirium. Changes appeared not be associated with demographic or clinical characteristics, suggesting that evidence from cross-sectional studies of motor subtypes could be applied to many individuals with delirium. Further longitudinal studies should be performed to clarify the stability of motor subtypes in different clinical populations

Assessment of behavioral disorders is one of the most commonly encountered tasks in child psychiatry. The Eyberg Child Behavior Inventory (ECBI) is a widespread measurement tool used for assessing conduct problems, though the psychometric properties of the tool have varied in different samples. In this study, the ECBI was evaluated in a Finnish population based sample of children aged 4 to 12 years (n = 1,715). Factor structure and internal consistency of the ECBI and associates of behavioral problems in Finnish children were evaluated. The results showed that a unidimensional one‐factor solution for the ECBI intensity scale was the best fit for the data. The ECBI mean scores were considerably higher in our sample compared to other Nordic countries. Boys scored higher than girls on both ECBI scales, and the mean scores decreased with child's age. Socioeconomic status (SES) was weakly connected to the ECBI scores. Our results highlight the need for country specific reference norms in order to improve the clinical utility of evidence‐based measures for assessing conduct problems.

The prevalence and associated factors of daily life restrictions due to a gluten-free diet in adult celiac disease patients diagnosed in childhood are poorly known. We investigated these issues by collecting the medical data of 955 pediatric patients and sending questionnaires evaluating various health outcomes to the 559 patients who had reached adulthood. Of the 231 respondents, 46% reported everyday life restrictions caused by dietary treatment. Compared with those without restrictions, they more often had anemia at diagnosis (37% vs. 22%, p = 0.014), but the groups were comparable in other diagnostic features. In adulthood, patients with restrictions reported more overall symptoms (32% vs. 17%, p = 0.006), although the symptoms measured with the Gastrointestinal Symptom Rating Scale questionnaire were comparable. Despite strict dietary adherence in both groups, the experience of restrictions was associated with dietary challenges (34% vs. 9%, p &lt, 0.001), health concerns (22% vs. 13%, p = 0.050), and lower vitality scores in the Psychological General Well-Being questionnaire. The groups did not differ in their current age, socioeconomic status, family history of celiac disease, general health or health-related lifestyle, the presence of co-morbidities, or regular follow up. Our results encourage healthcare professionals to discuss the possible health concerns and dietary challenges with patients to avoid unnecessary daily life restrictions, especially when young patients start to take responsibility for their treatment.

Objectives Developing disease modifying therapies for Parkinson’s disease (PD) calls for outcome measurement strategies focused on characterizing early stage disease progression. We explored the psychometric evidence for using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part II (patient motor experience of daily living) and part III (clinician motor examination) in this context. Methods MDS-UPDRS-II and -III data were collected at screening, month 12, and month 24 from 384 early stage PD patients (diagnosis ≤ 2 years; Hoehn and Yahr stage 1/2) in the Parkinson’s Progression Markers Initiative (PPMI) study. Psychometric analysis, based on Rasch measurement theory (RMT), was performed on both the original MDS UPDRS-II and -III scales and exploratory content-driven scale structures. Results RMT analyses showed neither scale was well targeted to early PD. A marked floor effect appeared for most items and a clear item gap was consistently observed in very mild severity of motor signs and levels of motor impact. The original MDS-UPDRS-II and -III scales also displayed disordered thresholds (9/13 and 20/33 items, respectively), indicating response scales not functioning as expected, and misfit (5/13 and 12/33 items, respectively), flagging areas for potential improvement. Conclusions The MDS-UPDRS-II and -III have psychometric limitations which limits the precision of measurement of motor symptoms and impact in early PD. This can lead to insensitivity in detecting differences and clinical change. Importantly, the diagnostic psychometric evidence provided by the RMT analysis provides a clear starting point for how to improve the quantification of clinically relevant concepts to characterize the course of early PD. Electronic supplementary material The online version of this article (10.1007/s00415-019-09348-3) contains supplementary material, which is available to authorized users.

Author(s): Chahine, Lana M; Siderowf, Andrew; Barnes, Janel; Seedorff, Nicholas; Caspell-Garcia, Chelsea; Simuni, Tanya; Coffey, Christopher S; Galasko, Douglas; Mollenhauer, Brit; Arnedo, Vanessa; Daegele, Nichole; Frasier, Mark; Tanner, Caroline; Kieburtz, Karl; Marek, Kenneth; The Parkinson’s Progression Markers Initiative | Abstract: BackgroundImproved prediction of Parkinson's disease (PD) progression is needed to support clinical decision-making and to accelerate research trials.ObjectivesTo examine whether baseline measures and their 1-year change predict longer-term progression in early PD.MethodsParkinson's Progression Markers Initiative study data were used. Participants had disease duration ≤2 years, abnormal dopamine transporter (DAT) imaging, and were untreated with PD medications. Baseline and 1-year change in clinical, cerebrospinal fluid (CSF), and imaging measures were evaluated as candidate predictors of longer-term (up to 5 years) change in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score and DAT specific binding ratios (SBR) using linear mixed-effects models.ResultsAmong 413 PD participants, median follow-up was 5 years. Change in MDS-UPDRS from year-2 to last follow-up was associated with disease duration (β= 0.351; 95% CI = 0.146, 0.555), male gender (β= 3.090; 95% CI = 0.310, 5.869), and baseline (β= -0.199; 95% CI = -0.315, -0.082) and 1-year change (β= 0.540; 95% CI = 0.423, 0.658) in MDS-UPDRS; predictors in the model accounted for 17.6% of the variance in outcome. Predictors of percent change in mean SBR from year-2 to last follow-up included baseline rapid eye movement sleep behavior disorder score (β= -0.6229; 95% CI = -1.2910, 0.0452), baseline (β= 7.232; 95% CI = 2.268, 12.195) and 1-year change (β= 45.918; 95% CI = 35.994,55.843) in mean striatum SBR, and 1-year change in autonomic symptom score (β= -0.325;95% CI = -0.695, 0.045); predictors in the model accounted for 44.1% of the variance.ConclusionsBaseline clinical, CSF, and imaging measures in early PD predicted change in MDS-UPDRS and dopamine-transporter binding, but the predictive value of the models was low. Adding the short-term change of possible predictors improved the predictive value, especially for modeling change in dopamine-transporter binding.

Early onset cerebellar Ataxia (EOAc) comprises a large group of rare heterogeneous disorders. Determination of the underlying etiology can be difficult given the broad differential diagnosis and the complexity of the genotype-phenotype relationships. This may change the diagnostic work-up into a time-consuming, costly and not always rewarding task. In this overview, the Childhood Ataxia and Cerebellar Group of the European Pediatric Neurology Society (CACG-EPNS) presents a diagnostic algorithm for EOAc patients. In seven consecutive steps, the algorithm leads the clinician through the diagnostic process, including EOA identification, application of the Inventory of Non-Ataxic Signs (INAS), consideration of the family history, neuro-imaging, laboratory investigations, genetic testing by array CGH and Next Generation Sequencing (NGS). In children with EOAc, this algorithm is intended to contribute to the diagnostic process and to allow uniform data entry in EOAc databases. (C) 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Recent longitudinal neuroimaging studies in patients with electroconvulsive therapy (ECT) suggest local effects of electric stimulation (lateralized) occur in tandem with global seizure activity (generalized). We used electric field (EF) modeling in 151 ECT treated patients with depression to determine the regional relationships between EF, unbiased longitudinal volume change, and antidepressant response across 85 brain regions. The majority of regional volumes increased significantly, and volumetric changes correlated with regional electric field (t = 3.77, df = 83, r = 0.38, p=0.0003). After controlling for nuisance variables (age, treatment number, and study site), we identified two regions (left amygdala and left hippocampus) with a strong relationship between EF and volume change (FDR corrected p, eLife digest Electroconvulsive therapy, or ECT for short, can be an effective treatment for severe depression. Many patients who do not respond to medication find that their symptoms improve after ECT. During an ECT session, the patient is placed under general anesthesia and two electrodes are attached to the scalp to produce an electric field that generates currents within the brain. These currents activate neurons and make them fire, causing a seizure, but it remains unclear how this reduces symptoms of depression. For many years, researchers thought that the induced seizure must be key to the beneficial effects of ECT, but recent studies have cast doubt on this idea. They show that increasing the strength of the electric field alters the clinical effects of ECT, without affecting the seizure. This suggests that the benefits of ECT depend on the electric field itself. Argyelan et al. now show that electric fields affect the brain by making a part of the brain known as the gray matter expand. In a large multinational study, 151 patients with severe depression underwent brain scans before and after a course of ECT. The scans revealed that the gray matter of the patients’ brains expanded during the treatment. The patients who experienced the strongest electric fields showed the largest increase in brain volume, and individual brain areas expanded if the electric field within them exceeded a certain threshold. This effect was particularly striking in two areas, the hippocampus and the amygdala. Both of these areas are critical for mood and memory. Further studies are needed to determine why the brain expands after ECT, and how long the effect lasts. Another puzzle is why the improvements in depression that the patients reported after their treatment did not correlate with changes in brain volume. Disentangling the relationships between ECT, brain volume and depression will ultimately help develop more robust treatments for this disabling condition.

Background:Gender differences in symptomatology in chronic schizophrenia and first episode psychosis patients have often been reported. However, little is known about gender differences in those at risk of psychotic disorders. This study investigated gender differences in symptomatology, drug use, comorbidity (i.e. substance use, affective and anxiety disorders) and global functioning in patients with an at-risk mental state (ARMS) for psychosis.Methods:The sample consisted of 336 ARMS patients (159 women) from the prodromal work package of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI; 11 centers). Clinical symptoms, drug use, comorbidity and functioning were assessed at first presentation to an early detection center using structured interviews.Results:In unadjusted analyses, men were found to have significantly higher rates of negative symptoms and current cannabis use while women showed higher rates of general psychopathology and more often displayed comorbid affective and anxiety disorders. No gender differences were found for global functioning. The results generally did not change when corrected for possible cofounders (e.g. cannabis use). However, most differences did not withstand correction for multiple testing.Conclusions:Findings indicate that gender differences in symptomatology and comorbidity in ARMS are similar to those seen in overt psychosis and in healthy controls. However, observed differences are small and would only be reliably detected in studies with high statistical power. Moreover, such small effects would likely not be clinically meaningful.

Introduction: The Structured Interview of Reported Symptoms (SIRS-2) utilizes various strategies in the detection of simulated psychiatric disorders. The present study aimed to examine which of these strategies proves most useful in uncovering feigned attention deficit hyperactivity disorder (ADHD) in adulthood. Method: One-hundred seventy-one individuals instructed to feign ADHD were compared to 46 genuine patients with ADHD as well as 99 neurotypical controls in their reports provided on the SIRS-2. Results: Responses provided by simulators resembled those of genuine patients with ADHD on all SIRS-2 subscales with the exception of a supplementary scale tapping Overly Specified symptom reports, where a moderate effect emerged (d = 0.88). Classification accuracy remained low, with particularly poor sensitivity (sensitivity = 19.30%). Sensitivity was higher when the decision rules postulated in the first edition SIRS were applied instead of its successor's decision model, yet this increase in sensitivity came at the price of unacceptably low specificity. Conclusion: The present results call for a disorder-specific instrument for the detection of simulated ADHD and offer starting points for the development of such a tool.

Background Confirming treatment response in clinical trials for irritable bowel syndrome (IBS) is challenging, due to the lack of biomarkers and limitations of the currently available symptom assessment tools. The Experience Sampling Method (ESM) might overcome these limitations by collecting digital assessments randomly and repeatedly during daily life. This study evaluated differences in change in abdominal pain between real‐time (ie, ESM) and retrospective (ie, Gastrointestinal Symptom Rating Scale [GSRS] and an end‐of‐day symptom diary) measurements, using data of an RCT on escitalopram vs placebo in patients with IBS and comorbid panic disorder. Methods Twenty‐nine IBS patients with comorbid panic disorder were included in a 6‐month RCT. The GSRS, diary, and ESM were completed at baseline (t = 0) and after 3 (t = 3) and 6 months (t = 6). Linear mixed models were used. Key results Experience Sampling Method analyses revealed a significant interaction between escitalopram and time, and ESM abdominal pain scores were 1.4 points lower in the escitalopram group compared to placebo at t = 6 (on a 1‐to‐7 scale; P = 0.021). When including the interaction with momentary anxiety, the reduction in abdominal pain scores in escitalopram vs placebo was even more pronounced for higher levels of anxiety. Average GSRS‐ and end‐of‐day abdominal pain scores were not significantly different between escitalopram and placebo at t = 3 and 6. Conclusions & Inferences Real‐time ESM has the potential to capture treatment response more sensitively compared to a retrospective end‐of‐day GI symptom diary and the GSRS, by taking into account day‐to‐day symptom variability as well as momentary factors that might moderate treatment effect, such as anxiety., Differences between real‐time and retrospective symptom reports have been demonstrated cross‐sectionally in irritable bowel syndrome (IBS). We here demonstrate that the real‐time Experience Sampling Method (ESM) potentially captures treatment response more sensitively than retrospective reports, by taking into account day‐to‐day symptom variability and treatment‐modulating momentary factors.

Background:Delirium may be more prevalent in elderly outpatients than has long been assumed. However, it may be easily missed due to overlap with dementia. Our aim was to study delirium symptoms and underlying somatic disorders in psycho-geriatric outpatients.Methods:We performed a case-control study among outpatients that were referred to a psychiatric institution between January 1st and July 1st 2010 for cognitive evaluation. We compared 44 cases with DSM-IV delirium (24 with and 20 without dementia) to 44 controls with dementia only. All participants were aged 70 years or older. We extracted from the medical files (1) referral characteristics including demographics, medical history, medication use, and referral reasons, (2) delirium symptoms, scored with the Delirium Rating Scale-Revised-98, and (3) underlying disorders categorized as: drugs/intoxication, infection, metabolic/endocrine disturbances, cardiovascular disorders, central nervous system disorders, and other health problems.Results:At referral, delirium patients had significantly higher numbers of chronic diseases and medications, and more often a history of delirium and a recent hospital admission than controls. Most study participants, including those with delirium, were referred for evaluation of (suspected) dementia. The symptoms that occurred more frequently in cases were: sleep disturbances, perceptual abnormalities, delusions, affect lability, agitation, attention deficits, acute onset, and fluctuations. Drug related (68%), infectious (61%), and metabolic-endocrine (50%) disturbances were often involved.Conclusions:Detection of delirium and distinction from dementia in older outpatients was feasible but required detailed caregiver information about the presence, onset, and course of symptoms. Most underlying disorders could be managed at home.

Background:Delirium is a common neuropsychiatric syndrome with considerable heterogeneity in clinical profile. Rapid reliable identification of clinical subtypes can allow for more targeted research efforts.Methods:We explored the concordance in attribution of motor subtypes between the Delirium Motor Subtyping Scale 4 (DMSS-4) and the original Delirium Motor Subtyping Scale (DMSS) (assessed cross-sectionally) and subtypes defined longitudinally using the Delirium Symptom Interview (DSI).Results:We included 113 elderly patients developing DSM-IV delirium after hip-surgery [mean age 86.9 ± 6.6 years; range 65–102; 68.1% females; 25 (22.1%) had no previous history of cognitive impairment]. Concordance for the first measurement was high for both the DMSS-4 and original DMSS (k = 0.82), and overall for the DMSS-4 and DSI (k = 0.84). The DMSS-4 also demonstrated high internal consistency (McDonald's omega = 0.90). The DSI more often allocated an assessment to “no subtype” compared to the DMSS-4 and DMSS-11, which showed higher inclusion rates for motor subtypes.Conclusions:The DMSS-4 provides a rapid method of identifying motor-defined clinical subtypes of delirium and appears to be a reliable alternative to the more detailed and time-consuming original DMSS and DSI methods of subtype attribution. The DMSS-4, so far translated into three languages, can be readily applied to further studies of causation, treatment and outcome in delirium.

Background The aim of this study was to systematically investigate the effectiveness of hatha yoga in treating acute, chronic and/or treatment-resistant mood and anxiety disorders. Methods Medline, Cochrane Library, Current Controlled Trials, Clinical Trials. gov, NHR Centre for Reviews and Dissemination, PsycINFO and CINAHL were searched through June 2018. Randomized controlled trials with patients with mood and anxiety disorders were included. Main outcomes were continuous measures of severity of mood and anxiety symptoms. Cohen's d was calculated as a measure of effect size. Meta-analyses using a random effects model was applied to estimate direct comparisons between yoga and control conditions for depression and anxiety outcomes. Publication bias was visually inspected using funnel plots. Results Eighteen studies were found, fourteen in acute patients and four in chronic patients. Most studies were of low quality. For depression outcomes, hatha yoga did not show a significant effect when compared to treatment as usual, an overall effect size of Cohen's d -0.64 (95% CI = -1.41, 0.13) or to all active control groups, Cohen's d -0.13 (95% CI = -0.49, 0.22). A sub-analysis showed that yoga had a significant effect on the reduction of depression compared to psychoeducation control groups, Cohen's d -0.52 (95% CI = -0.96, -0.08) but not to other active control groups, Cohen's d 0.28 (95% CI = -0.07, 0.63) For studies using a follow-up of six months or more, hatha yoga had no effect on the reduction of depression compared to active control groups, Cohen's d -0.14 (95% CI = -0.60, 0.33). Regarding anxiety, hatha yoga had no significant effect when compared to active control groups, Cohen's d -0.09 (95% CI = -0.47, 0.30). The I-2 and Q-statistic revealed heterogeneity amongst comparisons. Qualitative analyses suggest some promise of hatha yoga for chronic populations. Conclusions The ability to draw firm conclusions is limited by the notable heterogeneity and low quality of most of the included studies. With this caveat in mind, the results of the current meta-analysis suggest that hatha yoga does not have effects on acute, chronic and/or treatment-resistant mood and anxiety disorders compared to treatment as usual or active control groups. However, when compared to psychoeducation, hatha yoga showed more reductions in depression. It is clear that more high-quality studies are needed to advance the field.

Background Subcutaneous apomorphine infusion is a clinically established therapy for patients with Parkinson's disease with motor fluctuations not optimally controlled by oral medication. Open-label studies have shown that apomorphine infusion is effective in reducing off time (periods when antiparkinsonian drugs have no effect), dyskinesias, and levodopa dose, but confirmatory evidence from double-blind, controlled studies is lacking. We aimed to investigate the efficacy and safety of apomorphine infusion compared with placebo in patients with Parkinson's disease with persistent motor fluctuations despite optimised oral or transdermal treatment.Methods In this randomised, placebo-controlled, double-blind, multicentre trial, we enrolled patients at 23 European hospitals who had been diagnosed with Parkinson's disease more than 3 years previously and had motor fluctuations not adequately controlled by medical treatment. Patients were randomly assigned (1:1) with a computer-generated randomisation code, stratified by site, to receive 3-8 mg/h apomorphine or placebo saline infusion during waking hours (16 h a day [range 14-18 was acceptable]) for 12 weeks. The flow rate of the study drug and other oral medications could be adjusted during the first 4 weeks on the basis of individual efficacy and tolerability, after which patients entered an 8-week maintenance period. The primary endpoint was the absolute change in daily off time based on patient's diaries, and was assessed in the full analysis set, which was defined as all patients who received at least one dose of allocated study drug and had efficacy data available at any timepoint post-baseline. Safety was assessed in all patients who received at least one dose of apomorphine or placebo. All study participants and investigators were masked to treatment assignment. Both the 12-week double-blind phase and the 52-week open-label phase of this study are now complete; this paper reports results for the double-blind phase only. This study is registered with ClinicalTrials. gov (NCT02006121).Findings Between March 3, 2014, and March 1, 2016, 128 patients were screened for eligibility and 107 were randomly assigned, of whom 106 were included in the full analysis set (n=53 in both groups). Apomorphine infusion (mean final dose 4.68 mg/h [SD 1.50]) significantly reduced off time compared with placebo (-2.47 h per day [SD 3.70] in the apomorphine group vs -0.58 h per day [2.80] in the placebo group; difference -1.89 h per day, 95% CI -3.16 to -0.62; p=0.0025). Apomorphine was well tolerated without any unexpected safety signals. Six patients in the apomorphine group withdrew from the study because of treatment-related adverse events.Interpretation Apomorphine infusion results in a clinically meaningful reduction in off time in patients with Parkinson's disease with persistent motor fluctuations despite optimised oral or transdermal therapy. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

Aim Evidence suggests microvascular dysfunction (wider retinal venules and narrower arterioles) in schizophrenia (SCZ) and bipolar disorder (BD). The vascular development is synchronous with neuronal development in the retina and brain. The retinal vessel trajectory is related to retinal nerve fiber layer thinning and cerebrovascular abnormalities in SCZ and BD and has not yet been examined. Hence, in this study we examined the retinal vascular trajectory in SCZ and BD in comparison with healthy volunteers (HV). Methods Retinal images were acquired from 100 HV, SCZ patients, and BD patients, respectively, with a non-mydriatic fundus camera. Images were quantified to obtain the retinal arterial and venous trajectories using a validated, semiautomated algorithm. Analysis of covariance and regression analyses were conducted to examine group differences. A supervised machine-learning ensemble of bagged-trees method was used for automated classification of trajectory values. Results There was a significant difference among groups in both the retinal venous trajectory (HV: 0.17 +/- 0.08; SCZ: 0.25 +/- 0.17; BD: 0.27 +/- 0.20; P

OBJECTIVE: Chronic pain is a disabling illness, often comorbid with depression. We performed a randomized controlled pilot study on mindfulness-based cognitive therapy (MBCT) targeting depression in a chronic pain population.METHOD: Participants with chronic pain lasting ≥ 3 months; DSM-IV major depressive disorder (MDD), dysthymic disorder, or depressive disorder not otherwise specified; and a 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C₁₆) score ≥ 6 were randomly assigned to MBCT (n = 26) or waitlist (n = 14). We adapted the original MBCT intervention for depression relapse prevention by modifying the psychoeducation and cognitive-behavioral therapy elements to an actively depressed chronic pain population. We analyzed an intent-to-treat (ITT) and a per-protocol sample; the per-protocol sample included participants in the MBCT group who completed at least 4 of 8 sessions. Changes in scores on the QIDS-C₁₆ and 17-item Hamilton Depression Rating Sale (HDRS₁₇) were the primary outcome measures. Pain, quality of life, and anxiety were secondary outcome measures. Data collection took place between January 2012 and July 2013.RESULTS: Nineteen participants (73%) completed the MBCT program. No significant adverse events were reported in either treatment group. ITT analysis (n = 40) revealed no significant differences. Repeated-measures analyses of variance for the per-protocol sample (n = 33) revealed a significant treatment × time interaction (F₁,₃₁ = 4.67, P = .039, η²p = 0.13) for QIDS-C₁₆ score, driven by a significant decrease in the MBCT group (t₁₈ = 5.15, P < .001, d = >1.6), but not in the control group (t₁₃ = 2.01, P = .066). The HDRS₁₇ scores did not differ significantly between groups. The study ended before the projected sample size was obtained, which might have prevented effect detection in some outcome measures.CONCLUSIONS: MBCT shows potential as a treatment for depression in individuals with chronic pain, but larger controlled trials are needed.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01473615.

Objective: A growing body of research questions the reliance of symptom self-reports in the clinical evaluation of attention-deficit/hyperactivity disorder (ADHD) in adulthood. A recent study suggested that also impairment reports are vulnerable to noncredible responses, as derived from a simulation design using a global functional impairment scale. The present study aims to add evidence to this issue, by using an ADHD specific impairment scale in a simulation design on large samples. Method: Impairment ratings on the Weiss Functional Impairment Rating Scale (WFIRS) of 62 patients with ADHD were compared to 142 healthy individuals who were instructed to show normal behavior. Furthermore, impairment ratings of patients with ADHD were compared to ratings of 330 healthy individuals who were randomly assigned to one of four simulation conditions that were instructed to complete the scale as if they had ADHD. Results: Patients with ADHD reported higher levels of impairment than the healthy control group in all domains of life. Furthermore, individuals instructed to feign ADHD indicated higher levels of impairments in most domains of life compared to control participants and genuine patients with ADHD. The group differences between individuals feigning ADHD and individuals with genuine ADHD, however, were only small to moderate. Further analyses revealed that the WFRIS was not useful to successfully differentiate genuine from feigned ADHD. Conclusions: The present study confirms the conclusion that self-reported impairments are susceptible to noncredible responses and should be used with caution in the clinical evaluation of adult ADHD.

Objectives: Several approaches, ranging from self-ratings of symptoms and impairments to objective neuropsychological testing, have been utilized during clinical evaluation in order to assess symptom and performance validity of individuals with attention-deficit/hyperactivity disorder (ADHD) in adulthood. Motor activity has not been considered yet in this context, which is surprising given that hyperactivity is a prominent characteristic of ADHD. Hence, the goal of the present study was to explore the incremental value of motor activity when assessing the credibility of individuals with adult ADHD at clinical evaluation.Method: Forty-six patients diagnosed with ADHD took part in the study. A simulation design was performed, in which 152 healthy individuals were allocated to either a control condition (n=36) or one of three simulation conditions (n=116), the latter requesting participants to feign ADHD. All participants completed a self-rating scale of cognitive functioning and performed a computerized test for vigilance. Body movements were recorded during vigilance testing via a motion tracker attached to the back of the participant's chair.Results: Patients with ADHD reported significantly more pronounced cognitive complaints and performed significantly poorer on the vigilance test than control participants. Simulators of ADHD, as compared to genuine patients, showed excessively low performance on the vigilance test. However, neither self-ratings of cognitive functioning nor measures of motor activity were suitable to distinguish genuine from feigned ADHD. A hierarchical logistic regression model showed that motor activity had no incremental value in detecting feigned ADHD when vigilance test performance has already been considered.Conclusions: Standard neuropsychological tests of vigilance may be useful to measure both performance and credibility of individuals with adult ADHD at clinical evaluation. In contrast, self-reports of symptoms and impairments, as well as measures of body movements, may not support the assessment of credibility in this context.

Introduction: Clinical differentiation between bipolar disorder (BD) and major depressive disorder (MDD) is difficult. Research has therefore focused on discriminatory biological markers. Previous studies in MDD reported T cell deficits, while the limited studies in BD reported T cell activation. Studies directly comparing circulating numbers of T cells and T cell subsets between BD and MDD are lacking. The studies in the MOODINFLAME consortium make such a comparison possible.Methods: The number of circulating leukocyte populations (lymphocytes, monocytes, NK cells, B cells, T cells, CD3+CD8+ T cytotoxic cells, CD3+CD4+ T helper cells, Th1, Th2, Th17 and T regulatory cells) was determined using FACS technology in a cohort of 83 euthymic BD patients, 8 BD patients with a current mood episode and 165 healthy controls (HC). Data were compared to those of 34 moderately and 56 severely depressed MDD patients.Results: Compared to MDD patients, BD patients showed significantly increased levels of Th17, Th2, Th1 and T regulatory cells (all p Conclusion: This study shows CD4+ T helper cell deficits in MDD patients, while normal or even raised levels of these cells were found in BD patients. The differences in CD4+ T helper cell differentiation was most outspoken for Th17 cells.

BACKGROUND: Retrospective questionnaires are frequently used for symptom assessment in irritable bowel syndrome (IBS) patients, but are influenced by recall bias and circumstantial and psychological factors. These limitations may be overcome by random, repeated, momentary assessment during the day, using electronic Experience Sampling Methodology (ESM). Therefore, we compared symptom assessment by ESM to retrospective paper questionnaires in IBS patients. METHODS: Twenty-six IBS patients (Rome III) were included, of which 16 were diagnosed with panic disorder (DSM-IV-TR). Patients scored symptoms using end-of-day diaries during 14 days and the gastrointestinal symptom rating scale (GSRS) once. ESM was used on seven consecutive days during the same time period. KEY RESULTS: End-of-day diary abdominal pain scores were 0.4 (SE 0.1, p < 0.001) point higher (on a 1-to-5-point scale) compared to corresponding ESM mean-scores in IBS patients. The difference was even more pronounced for upper abdominal pain scores assessed by the GSRS (4.77 +/- 1.50) compared to ESM mean-scores (2.44 +/- 1.30, p < 0.001), both on 1-to-7-point scale. For flatulence, comparable results were found. Nausea and belching scores showed small, but significant differences between end-of-day diary and ESM. All tested symptoms were scored higher on GSRS compared to ESM mean-scores (p < 0.01). Affective comorbidity did not influence differences in pain reporting between methods. CONCLUSIONS & INFERENCES: IBS patients report higher scores for abdominal pain in retrospective questionnaires compared to ESM, with a tendency to report peak rather than average pain scores. ESM can provide more insight in symptom course and potential triggers, and may lead to a better understanding of IBS symptomatology.

Background Previous studies have reported MRI abnormalities of the corpus callosum (CC) in patients with bipolar disorder (BD), although only a few studies have directly compared callosal areas in psychotic versus nonpsychotic patients with this disorder. We sought to compare regional callosal areas in a large international multicentre sample of patients with BD and healthy controls. Methods We analyzed anatomic T-1 MRI data of patients with BD-I and healthy controls recruited from 4 sites (France, Germany, Ireland and the United States). We obtained the mid-sagittal areas of 7 CC subregions using an automatic CC delineation. Differences in regional callosal areas between patients and controls were compared using linear mixed models (adjusting for age, sex, handedness, brain volume, history of alcohol abuse/dependence, lithium or antipsychotic medication status, symptomatic status and site) and multiple comparisons correction. We also compared regional areas of the CC between patients with BD with and without a history of psychotic features. Results We included 172 patients and 146 controls in our study. Patients with BD had smaller adjusted mid-sagittal CC areas than controls along the posterior body, the isthmus and the splenium of the CC. Patients with a positive history of psychotic features had greater adjusted area of the rostral CC region than those without a history of psychotic features. Limitations We found small to medium effect sizes, and there was no calibration technique among the sites. Conclusion Our results suggest that BD with psychosis is associated with a different pattern of interhemispheric connectivity than BD without psychosis and could be considered a relevant neuroimaging subtype of BD.

STUDY DESIGN: A prospective cohort study, with assessments before, at 3 months after, and at 12 months after total knee arthroplasty (TKA).OBJECTIVES: To determine and compare the responsiveness and reliability of the Patient-Specific Functional Scale (PSFS) in patients undergoing a TKA.BACKGROUND: Reliable and valid measurement instruments are important to measure functional status. The PSFS is frequently used in several patient populations, but its methodological characteristics in a population of patients with TKA in the perioperative phases of surgery are unknown.METHODS: The PSFS, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and global perceived effect (GPE) were administered at 3 time points in 150 patients undergoing a TKA. Correlations, effect sizes, and standardized response Means were calculated. The PSFS was administered twice to assess its reliability in terms of intraclass correlation coefficients and limits of agreement.RESULTS: The correlation coefficients between the PSFS and WOMAC at 3 months and 1 year were 0.41 and 0.48, respectively; those between the PSFS and GPE were -0.37 and -0.55, respectively. The effect sizes of the PSFS at 3 months and 1 year were 1.71 and 2.89, respectively; those of the WOMAC were 1.45 and 1.64, respectively. The standardized response means of the PSFS at 3 months and 1 year were 0.96 and 1.48, respectively; those of the WOMAC were 1.28 and 1.37, respectively. The intraclass correlation coefficients ranged between 0.73 and 0.86. The systematic error was between 0.12 and 0.54. The limits of agreement ranged from +/- 2.17 to +/- 2.72.CONCLUSION: The reliability of the PSFS is good. Its responsiveness is high, especially in the long term. However, the PSFS cannot be used interchangeably with the WOMAC in the immediate postoperative period.

Until relatively recently, long-acting injectable (LAI) formulations were only available for first-generation antipsychotics and their utilization decreased as use of oral second-generation antipsychotics (SGA) increased. Although registry-based naturalistic studies show LAIs reduce rehospitalization more than oral medications in clinical practice, this is not seen in recent randomized clinical trials. PROACTIVE (Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy) relapse prevention study incorporated efficacy and effectiveness features. At 8 US academic centers, 305 patients with schizophrenia or schizoaffective disorder were randomly assigned to LAI risperidone (LAI-R) or physician's choice oral SGAs. Patients were evaluated during the 30-month study by masked, centralized assessors using 2-way video, and monitored biweekly by on-site clinicians and assessors who knew treatment assignment. Relapse was evaluated by a masked Relapse Monitoring Board. Differences between LAI-R and oral SGA treatment in time to first relapse and hospitalization were not significant. Psychotic symptoms and Brief Psychiatric Rating Scale total score improved more in the LAI-R group. In contrast, the LAI group had higher Scale for Assessment of Negative Symptoms Alogia scale scores. There were no other between-group differences in symptoms or functional improvement. Despite the advantage for psychotic symptoms, LAI-R did not confer an advantage over oral SGAs for relapse or rehospitalization. Biweekly monitoring, not focusing specifically on patients with demonstrated nonadherence to treatment and greater flexibility in changing medication in the oral treatment arm, may contribute to the inability to detect differences between LAI and oral SGA treatment in clinical trials.

Mood is a key element of Major Depressive Disorder (MDD), and is perceived as a highly dynamic construct. The aim of the current study was to examine whether a single-item mood scale can be used for mood monitoring. One hundred thirty remitted out-patients were assessed using the Structured Clinical Interview for DSM-IV Axis-I Disorders (SCID-I), Visual Analogue Mood Scale (VAMS), 17-item Hamilton Depression Rating Scale (HAM-D17), and Inventory of Depressive Symptomatology-Self Report (IDS-SR). Of all patients, 13.8% relapsed during follow-up assessments. Area under the curves (AUCs) for the VAMS, HAM-D17 and IDS-SR were 0.94, 0.91, and, 0.86, respectively. The VAMS had the highest positive predictive value (PPV) without any false negatives at score 55 (PPV=0.53; NPV=1.0) and was the best predictor of current relapse status (variance explained for VAMS: 60%; for HAM-D17: 49%; for IDS-SR: 34%). Only the HAM-D17 added significant variance to the model (7%). Assessing sad mood with a single-item mood scale seems to be a straightforward and patient-friendly avenue for life-long mood monitoring. Using a diagnostic interview (e.g., the SCID) in case of a positive screen is warranted. Repeated assessment of the VAMS using Ecological Momentary Assessment (EMA) might reduce false positives.

Background: The anterior cingulate cortex (ACC) plays an important role in the neuropathology of major depressive disorder (MDD). So far, the effect of local cortical alteration on metabolites in multiple subdivisions of ACC has not been studied. We aimed to investigate structural and biochemical changes and their relationship in the pregenual ACC (pgACC), dorsal ACC (dACC) in MDD.Methods: We obtained magnetic resonance spectroscopy (MRS) in two investigated regions for 24 depressed patients and matched controls. In each region, cortical thickness (CTh) was calculated within a template mask based on its MRS voxel. We investigated neurotransmitter concentrations of Glx, N-acetyl aspartate (NAA), and myo-inositol (m-lns) in two investigated regions, as well as their relationships with CTh in depressed individuals and healthy controls.Results: Patients showed significantly lower cortical thickness in dACC compared to controls. Glx in dACC significantly correlated with CTh in healthy controls but not MDD patients, while NAA and CTh in dACC significantly correlated in both groups. A marginal decrease of Glx in pgACC was found in the subgroup of more severely depressive patients, compared to the mildly depressed patients.Limitations: Modest sample size and lack of episodes of depression may limit the generalizability of our findings.Conclusion: Our results indicate an abolished CTh-MRS relation in dACC associated with structural decline but not in pgACC, where acute MRS alterations prevailed. Our study provides the first evidence of a neurochemical basis explaining some of the inter-individual variability in CTh in MDD. (C) 2014 Elsevier B.V. All rights reserved.

Objective:Differential associations of symptom dimensions with prognosis in myocardial infarction (MI) patients have been shown for depression, but no studies have focused on anxiety dimensions. The aim of this study was to assess the association between somatic and psychological symptoms of anxiety following acute MI with adverse prognosis and to assess the overlap between anxiety and depression dimensions.Method:Patients (n = 418) were assessed on demographic and clinical variables. The Hamilton Anxiety and Depression Rating Scales were used to measure anxiety and depression 2 months post-MI. Mean follow-up period was 3.8 years and the endpoint consisted of all-cause mortality and recurrent MI.Results:After adjustment for demographic and clinical variables, somatic anxiety was significantly associated with recurrent MI and mortality (HR: 1.32; 95% CI [1.03, 1.69]; p = .03), and a trend was shown for an association between psychological anxiety and outcome (HR: 1.29; 95% CI [0.99, 1.67]; p = .06). The total anxiety score of the HARS was the strongest predictor of recurrent MI and mortality (HR: 1.38; 95% CI [1.07, 1.78]; p = .02). The HARS and the HDRS were highly correlated (r = .86; p < .01). Dimensions consisting of psychological distress (HR: 1.29; 95% CI [1.02, 1.63]; p = .03) and cardiopulmonary/autonomic symptoms (HR: 1.36; 95% CI [1.06, 1.75]; p = .02) also predicted outcome in adjusted analyses.Conclusions:Anxiety was associated with adverse prognosis in MI patients with significant associations for somatic anxiety and total anxiety. When combining anxiety and depression items, psychological distress and cardiopulmonary/autonomic symptoms predicted recurrent MI and mortality. Future research might better focus on dimensions of anxiety and depression simultaneously in MI patients.