Negative symptoms predict high relapse rates and both predict less favorable functional outcome in first episode psychosis, independent of treatment strategy

BACKGROUND: In first episode psychosis (FEP) baseline negative symptoms (BNS) and relapse both predict less favorable functional outcome. Relapse-prevention is one of the most important goals of treatment. Apart from discontinuation of antipsychotics, natural causes of relapse are unexplained. We hypothesized that BNS, apart from predicting worse functional outcome, might also increase relapse risk. METHODS: We performed a post-hoc analysis of 7-year follow-up data of a FEP cohort (n = 103) involved in a dose-reduction/discontinuation (DR) vs. maintenance treatment (MT) trial. We examined: 1) what predicted relapse, 2) what predicted functional outcome, and 3) if BNS predicted relapse, whether MT reduced relapse rates compared to DR. After remission patients were randomly assigned to DR or MT for 18 months. Thereafter, treatment was uncontrolled. OUTCOMES: BNS and duration of untreated psychosis (DUP) predicted relapse. Number of relapses, BNS, and treatment strategy predicted functional outcome. BNS was the strongest predictor of relapse, while number of relapses was the strongest predictor of functional outcome above BNS and treatment strategy. Overall and within MT, but not within DR, more severe BNS predicted significantly higher relapse rates. Treatment strategies did not make a difference in relapse rates, regardless of BNS severity. INTERPRETATION: BNS not only predicted worse functional outcome, but also relapses during follow-up. Since current low dose maintenance treatment strategies did not prevent relapse proneness in patients with more severe BNS, resources should be deployed to find optimal treatment strategies for this particular group of patients

Reprint of:Negative symptoms predict high relapse rates and both predict less favorable functional outcome in first episode psychosis, independent of treatment strategy

Background: In first episode psychosis (FEP) baseline negative symptoms (BNS) and relapse both predict less favorable functional outcome. Relapse-prevention is one of the most important goals of treatment. Apart from discontinuation of antipsychotics, natural causes of relapse are unexplained. We hypothesized that BNS, apart from predicting worse functional outcome, might also increase relapse risk. Methods: We performed a post-hoc analysis of 7-year follow-up data of a FEP cohort (n = 103) involved in a dose-reduction/discontinuation (DR) vs. maintenance treatment (MT) trial. We examined: 1) what predicted relapse, 2) what predicted functional outcome, and 3) if BNS predicted relapse, whether MT reduced relapse rates compared to DR. After remission patients were randomly assigned to DR or MT for 18 months. Thereafter, treatment was uncontrolled. Outcomes: BNS and duration of untreated psychosis (DUP) predicted relapse. Number of relapses, BNS, and treatment strategy predicted functional outcome. BNS was the strongest predictor of relapse, while number of relapses was the strongest predictor of functional outcome above BNS and treatment strategy. Overall and within MT, but not within DR, more severe BNS predicted significantly higher relapse rates. Treatment strategies did not make a difference in relapse rates, regardless of BNS severity. Interpretation: BNS not only predicted worse functional outcome, but also relapses during follow-up. Since current low dose maintenance treatment strategies did not prevent relapse proneness in patients with more severe BNS, resources should be deployed to find optimal treatment strategies for this particular group of patients. (C) 2019 Elsevier B.V. All rights reserved

Some Siegel modular standard L-values, and Shafarevich–Tate groups

AbstractWe explain how the Bloch–Kato conjecture leads us to the following conclusion: a large prime dividing a critical value of the L-function of a classical Hecke eigenform f of level 1, should often also divide certain ratios of critical values for the standard L-function of a related genus two (and in general vector-valued) Hecke eigenform F. The relation between f and F (Harderʼs conjecture in the vector-valued case) is a congruence involving Hecke eigenvalues, modulo the large prime. In the scalar-valued case we prove the divisibility, subject to weak conditions. In two instances in the vector-valued case, we confirm the divisibility using elaborate computations involving special differential operators. These computations do not depend for their validity on any unproved conjecture

A single blind randomized controlled trial of cognitive behavioural therapy in a help-seeking population with an At Risk Mental State for psychosis: the Dutch Early Detection and Intervention Evaluation (EDIE-NL) trial

BACKGROUND: Psychotic disorders are a serious mental health problem. Intervention before the onset of psychosis might result in delaying the onset, reducing the impact or even preventing the first episode of psychosis. This study explores the effectiveness of cognitive behavioural therapy (CBT) in targeting cognitive biases that are involved in the formation of delusions in persons with an ultra-high risk for developing psychosis. A single blind randomised controlled trial compares CBT with treatment as usual in preventing or delaying the onset of psychosis. METHOD/DESIGN: All help seeking patients aged 14 to 35 years referred to the mental health services in three regions in the Netherlands are pre-screened with the Prodromal Questionnaire during a period of two years. Patients with a score of 18 or more on the sub-clinical positive symptoms items (45 items in total) will be assessed with the Comprehensive Assessment of At Risk Mental State (CAARMS). In a different pathway to care model all referrals from the mental health services in Amsterdam to the specialized psychosis clinic of the Academic Medical Centre in Amsterdam are also assessed with the CAARMS. The primary outcome is the transition rate to psychosis according to the CAARMS-criteria. Group differences will be analysed with chi-square tests and survival analyses. DISCUSSION: CBT is a highly tolerated treatment. The psycho-educational CBT approach may prove to be a successful strategy since most people with an At Risk Mental State (ARMS) are distressed by odd disturbing experiences. Giving explanations for and normalising these experiences may reduce the arousal (distress) and therefore may prevent people from developing a catastrophic delusional explanation for their odd experiences and thus prevent them from developing psychosis. Screening the entire help-seeking population referred to community mental health services with a two-stage strategy, as compared with traditional referral to a specialist clinical psychosis centre, might detect more ultra-high-risk (UHR) patients. This type of screening could be implemented in mental health care as routine screening. The trial is registered at Current Controlled trials as trial number ISRCTN21353122

Social Cognition in Individuals at Ultra-High Risk for Psychosis:A Meta-Analysis

Treatment in the ultra-high risk stage for a psychotic episode is critical to the course of symptoms. Markers for the development of psychosis have been studied, to optimize the detection of people at risk of psychosis. One possible marker for the transition to psychosis is social cognition. To estimate effect sizes for social cognition based on a quantitative integration of the published evidence, we conducted a meta-analysis of social cognitive performance in people at ultra high risk (UHR).A literature search (1970-July 2015) was performed in PubMed, PsychINFO, Medline, Embase, and ISI Web of Science, using the search terms 'social cognition', 'theory of mind', 'emotion recognition', 'attributional style', 'social knowledge', 'social perception', 'empathy', 'at risk mental state', 'clinical high risk', 'psychosis prodrome', and 'ultra high risk'. The pooled effect size (Cohen's D) and the effect sizes for each domain of social cognition were calculated. A random effects model with 95% confidence intervals was used.Seventeen studies were included in the analysis. The overall significant effect was of medium magnitude (d = 0.52, 95% Cl = 0.38-0.65). No moderator effects were found for age, gender and sample size. Sub-analyses demonstrated that individuals in the UHR phase show significant moderate deficits in affect recognition and affect discrimination in faces as well as in voices and in verbal Theory of Mind (TOM). Due to an insufficient amount of studies, we did not calculate an effect size for attributional bias and social perception/ knowledge. A majority of studies did not find a correlation between social cognition deficits and transition to psychosis, which may suggest that social cognition in general is not a useful marker for the development of psychosis. However some studies suggest the possible predictive value of verbal TOM and the recognition of specific emotions in faces for the transition into psychosis. More research is needed on these subjects.The published literature indicates consistent general impairments in social cognition in people in the UHR phase, but only very specific impairments seem to predict transition to psychosis

Measuring empathy in schizophrenia:The Empathic Accuracy Task and its correlation with other empathy measures

Introduction: Empathy is an interpersonal process impaired in schizophrenia. Past studies have mainly used questionnaires or performance-based tasks with static cues to measure cognitive and affective empathy. We used the Empathic Accuracy Task (EAT) designed to capture dynamic aspects of empathy by using videoclips in which perceivers continuously judge emotionally charged stories. We compared individuals with schizophrenia with a healthy comparison group and assessed correlations among EAT and three other commonly used empathy measures. Method: Patients (n = 92) and a healthy comparison group (n = 42) matched for age, gender and education completed the EAT, the Interpersonal Reactivity Index, Questionnaire of Cognitive and Affective Empathy and Faux Pas. Differences between groups were analyzed and correlations were calculated between empathy measurement instruments. Results: The groups differed in EAT performance, with the comparison group outperforming patients. A moderating effect was found for emotional expressivity of the target: while both patients and the comparison group scored low when judging targets with low expressivity, the comparison group performed better than patients with more expressive targets. Though there were also group differences on the empathy questionnaires, EAT performance did not correlate with questionnaire scores. Conclusions: Individuals with schizophrenia benefit less from the emotional expressivity of other people than the comparison group, which contributes to their impaired empathic accuracy. The lack of correlation between the EAT and the questionnaires suggests a distinction between self-report empathy and actual empathy performance. To explore empathic difficulties in real life, it is important to use instruments that take the interpersonal perspective into account. (C) 2019 Published by Elsevier B.V

A Smart Screening Device for Patients with Mental Health Problems in Primary Health Care:Development and Pilot Study

BACKGROUND: Adequate recognition of mental health problems is a prerequisite for successful treatment. Although most people tend to consult their general practitioner (GP) when they first experience mental health problems, GPs are not very well equipped to screen for various forms of psychopathology to help them determine clients' need for treatment. OBJECTIVE: In this paper, the development and characteristics of CATja, a computerized adaptive test battery built to facilitate triage in primary care settings, are described, and first results of its implementation are reported. METHODS: CATja was developed in close collaboration with GPs and mental health assistants (MHAs). During implementation, MHAs were requested to appraise clients' rankings (N=91) on the domains to be tested and to indicate the treatment level they deemed most appropriate for clients before test administration. We compared the agreement between domain score appraisals and domain score computed by CATja and the agreement between initial (before test administration) treatment level advice and final treatment level advice. RESULTS: Agreements (Cohen kappas) between MHAs' appraisals of clients' scores and clients' scores computed by CATja were mostly between .40 and .50 (Cohen kappas=.10-.20), and the agreement between "initial" treatment levels and the final treatment level advised was .65 (Cohen kappa=.55). CONCLUSIONS: Using CATja, caregivers can efficiently generate summaries of their clients' mental well-being on which decisions about treatment type and care level may be based. Further validation research is needed

T helper cell subsets specific for pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis

Background: We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis. Methods: Peripheral blood human memory CD4+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines. Results: Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood. Conclusions: Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions

Ethnicity and baseline symptomatology in patients with an At Risk Mental State for psychosis

Ethnicity has been associated with different incidence rates and different symptom profiles in young patients with psychotic-like disorders. No studies so far have examined the effect of ethnicity on symptoms in people with an At Risk Mental State (ARMS). In this cross-sectional study, we analysed the relationship between ethnicity and baseline data on the severity of psychopathology scores in 201 help-seeking patients who met the ARMS criteria and agreed to participate in the Dutch Early Detection and Intervention (EDIE-NL) trial. Eighty-seven of these patients had a non-Dutch ethnicity. We explored the possible mediating role of ethnic identity. Higher rates of negative symptoms, and of anhedonia in particular, were found in the ethnic minority group. This result could be attributed mainly to the Moroccan-Dutch and Turkish-Dutch subgroups, who also presented with more depression symptoms when the groups were examined separately. The ethnic minority group displayed a lower level of ethnic group identity compared to the immigrants of the International Comparative Study of Ethnocultural Youth (ICSEY). Ethnic identity was inversely related to symptoms in the Moroccan-Dutch patient group. The prevalence of more severe negative symptoms and depression symptoms in ethnic minority groups deserves more attention, as the experience of attenuated positive symptoms when accompanied by negative symptoms or distress has proven to be predictive for transition to a first psychotic episod