Feasibility and efficacy of an acceptance and mindfulness-based group intervention for young people with early psychosis (Feel-Good group)

Background: Over the last decade, researchers have sought for alternative interventions that have better treatment effects than Cognitive Behavioral Therapy (CBT) when treating psychotic symptoms. Mindfulness-based interventions have been a proposed alternative to CBT, yet research regarding its feasibility, acceptance and effectiveness is lacking when treating individuals with early psychosis in inpatient settings. Objective: Before conducting a large-scale randomized-controlled trial (RCT), this pilot study evaluated the feasibility and the potential efficacy of a mindfulness-based inpatient group intervention that targets emotion regulation in patients with early psychosis, and thus indirectly improving psychotic symptoms. Methods: A pre–post study was performed. Thirty-six patients with early psychosis treated at the specialized inpatient treatment “Frühinterventionsund Therapiezentrum; FRITZ” (early intervention and therapy center) received eight group therapy sessions. Assessments were performed at baseline, after 8 weeks post treatment and at follow-up after 16 weeks. Results: Rates of patients who participated in the study suggests that a mindfulness-based group therapy is highly accepted and feasible for patients with early psychosis being treated in an inpatient ward. Friedman analyses revealed significant changes in the primary outcomes of emotional goal attainment (Goal 1: W = 0.79; Goal 2: W = 0.71) and psychotic symptoms (PANSS-T: W = 0.74). Significant, albeit small, effect sizes were found in patients’ self-perception of emotion regulation skills (ERSQ: W = 0.23). Discussion: We found favorable findings regarding the feasibility and acceptance of the Feel-Good mindfulness-based intervention. Results of the study provide a basis for an estimation of an adequate sample size for a fully powered RCT that needs to be conducted to test whether Feel-Good is effective in the inpatient treatment of psychotic symptoms for individuals with early psychosis

Preventing and Reducing Coercive Measures—An Evaluation of the Implementation of the Safewards Model in Two Locked Wards in Germany

IntroductionAggression and violence are highly complex problems in acute psychiatry that often lead to the coercive interventions. The Safewards Model is an evidence-informed conflict-reduction strategy to prevent and reduce such incidents. The aim of this study was to evaluate the implementation of this model with regard to coercive interventions in inpatient care.Materials and MethodsWe evaluated outcomes of the implementation of the Safewards Model in two locked psychiatric wards in Germany. Frequency and duration of coercive interventions applied during a period of 11 weeks before and 11 weeks after the implementation period were assessed through routine data. Fidelity to the Safewards Model was assessed by the Organization Fidelity Checklist.ResultsFidelity to the Safewards Model was high in both wards. The overall use of coercive measures differed significantly between wards [case-wise: χ2 (1, n = 250) = 35.34, p ≤ 0.001; patient-wise: χ2 (1, n = 103) = 21.45, p ≤ 0.001] and decreased post-implementation. In one ward, the number of patients exposed to coercive interventions in relation to the overall number of Patients decreased significantly [χ2 (1, 281) = 6.40, p = 0.01]. Furthermore, the mean duration of coercive interventions overall declined significantly [U(55,21) = −2.142, p = 0.032] with an effect size of Cohen’s d = −0.282 (95% CI: −0.787, 0.222) in that ward. Both aspects declined as well in the other ward, but not significantly.DiscussionResults indicate that the implementation of the Safewards interventions according to the model in acute psychiatric care can reduce coercive measures. They also show the role of enabling factors as well as of obstacles for the implementation process

Efficacy of Integrated Social Cognitive Remediation vs. Neurocognitive Remediation in Improving Functional Outcome in Schizophrenia: Concept and Design of a Multicenter, Single-Blind RCT (The ISST Study)

Background: Although clinically effective treatment is available for schizophrenia, recovery often is still hampered by persistent poor psychosocial functioning, which in turn is limited by impairments in neurocognition, social cognition, and social behavioral skills. Although cognitive remediation has shown general efficacy in improving cognition and social functioning, effects still need to be improved and replicated in appropriately powered, methodologically rigorous randomized controlled trials (RCTs). Existing evidence indicates that effects can most likely be optimized by combining treatment approaches to simultaneously address both social cognitive and social behavioral processes. Objectives: To assess whether Integrated Social Cognitive and Behavioral Skill Therapy (ISST) ismore efficacious in improving functional outcome in schizophrenia than the active control treatment Neurocognitive Remediation Therapy (NCRT). Methods: The present study is a multicenter, prospective, rater-blinded, two-arm RCT being conducted at six academic study sites in Germany. A sample of 180 at least partly remitted patients with schizophrenia are randomly assigned to either ISST or NCRT. ISST is a compensatory, strategy-based program that targets social cognitive processes and social behavioral skills. NCRT comprisesmainly drill and practice-oriented neurocognitive training. Both treatments consist of 18 sessions over 6 months, and participants are subsequently followed up for another 6 months. The primary outcome is all-cause discontinuation over the 12-month study period; psychosocial functioning, quality of life, neurocognitive and social cognitive performance, and clinical symptoms are assessed as secondary outcomes at baseline before randomization (V1), at the end of the six-month treatment period (V6), and at the six-month follow-up (V12). Discussion: This RCT is part of the German Enhancing Schizophrenia Prevention and Recovery through Innovative Treatments (ESPRIT) research network, which aims at using innovative treatments to enhance prevention and recovery in patients with schizophrenia. Because this study is one of the largest and methodologically most rigorous RCTs on the efficacy of cognitive remediation approaches in schizophrenia, it will not only help to identify the optimal treatment options for improving psychosocial functioning and thus recovery in patients but also allow conclusions to be drawn about factors influencing and mediating the effects of cognitive remediation in these patients

DAOA/G72 predicts the progression of prodromal syndromes to first episode psychosis

The genetic factors determining the progression of prodromal syndromes to first episode schizophrenia have remained enigmatic to date. In a unique prospective multicentre trial, we assessed whether variants at the d-amino acid oxidase activator (DAOA)/G72 locus influence progression to psychosis. Young subjects with a prodromal syndrome were observed prospectively for up to 2 years to assess the incidence of progression to schizophrenia or first episode psychosis. Of the 82 probands with a prodromal syndrome, 21 probands experienced progression to psychosis within the observation period. Assessment of nine common variants in the DAOA/G72 locus yielded two variants with the predictive value for symptom progression: all four probands with the rs1341402 CC genotype developed psychosis compared with 17 out of 78 probands with the TT or CT genotypes (χ2 = 12.348; df = 2; p = 0.002). The relative risk for progression to psychosis was significantly increased in the CC genotype: RR = 4.588 (95% CI = 2.175–4.588). Similarly, for rs778294, 50% of probands with the AA genotype, but only 22% of probands with a GG or GA genotype progressed to psychosis (χ2 = 7.027; df = 2; p = 0.030). Moreover, haplotype analysis revealed a susceptibility haplotype for progression to psychosis. This is one of the first studies to identify a specific genetic factor for the progression of prodromal syndromes to schizophrenia, and further underscores the importance of the DAOA/G72 gene for schizophrenia

Prospective progression from high-prevalence disorders to bipolar disorder: exploring characteristics of pre-illness stages

BACKGROUND: Identification of risk factors within precursor syndromes, such as depression, anxiety or substance use disorders (SUD), might help to pinpoint high-risk stages where preventive interventions for Bipolar Disorder (BD) could be evaluated. METHODS: We examined baseline demographic, clinical, quality of life, and temperament measures along with risk clusters among 52 young people seeking help for depression, anxiety or SUDs without psychosis or BD. The risk clusters included Bipolar At-Risk (BAR) and the Bipolarity Index as measures of bipolarity and the Ultra-High Risk assessment for psychosis. The participants were followed up for 12 months to identify conversion to BD. Those who converted and did not convert to BD were compared using Chi-Square and Mann Whitney U tests. RESULTS: The sample was predominantly female (85%) and a majority had prior treatment (64%). Four participants converted to BD over the 1-year follow up period. Having an alcohol use disorder at baseline (75% vs 8%, χ(2)=14.1, p<0.001) or a family history of SUD (67% vs 12.5%, χ(2)=6.0, p=0.01) were associated with development of BD. The sub-threshold mania subgroup of BAR criteria was also associated with 12-month BD outcomes. The severity of depressive symptoms and cannabis use had high effects sizes of association with BD outcomes, without statistical significance. CONCLUSIONS AND LIMITATIONS: The small number of conversions limited the power of the study to identify associations with risk factors that have previously been reported to predict BD. However, subthreshold affective symptoms and SUDs might predict the onset of BD among help-seeking young people with high-prevalence disorders

Bipolar at-risk criteria: an examination of which clinical features have optimal utility for identifying youth at risk of early transition from depression to bipolar disorders

Background: A clinical and research challenge is to identify which depressed youth are at risk of “early transition to bipolar disorders (ET-BD).” This 2-part study (1) examines the clinical utility of previously reported BD at-risk (BAR) criteria in differentiating ET-BD cases from unipolar depression (UP) controls; and (2) estimates the Number Needed to Screen (NNS) for research and general psychiatry settings. Methods: Fifty cases with reliably ascertained, ET-BD I  and II cases were matched for gender and birth year with 50 UP controls who did not develop BD over 2 years. We estimated the clinical utility for finding true cases and screening out non-cases for selected risk factors and their NNS. Using a convenience sample (N = 80), we estimated the NNS when adjustments were made to account for data missing from clinical case notes. Results: Sub-threshold mania, cyclothymia, family history of BD, atypical depression symptoms and probable antidepressant-emergent elation, occurred significantly more frequently in ET-BD youth. Each of these “BARDepression” criteria demonstrated clinical utility for screening out non-cases. Only cyclothymia demonstrated good utility for case finding in research settings; sub-threshold mania showed moderate utility. In the convenience sample, the NNS for each criterion ranged from ~4 to 7.  Conclusions: Cyclothymia showed the optimum profile for case finding, screening and NNS in research settings. However, its presence or absence was only reported in 50% of case notes. Future studies of ET-BD instruments should distinguish which criteria have clinical utility for case finding vs screening

Association between cannabis use and symptom dimensions in schizophrenia spectrum disorders: an individual participant data meta-analysis on 3053 individuals

Background: The association between cannabis use and positive symptoms in schizophrenia spectrum disorders is well documented, especially via meta-analyses. Yet, findings are inconsistent regarding negative symptoms, while other dimensions such as disorganization, depression, and excitement, have not been investigated. In addition, meta-analyses use aggregated data discarding important confounding variables which is a source of bias. Methods: PubMed, ScienceDirect and PsycINFO were used to search for publications from inception to September 27, 2022. We contacted the authors of relevant studies to extract raw datasets and perform an Individual Participant Data meta-analysis (IPDMA). Inclusion criteria were: psychopathology of individuals with schizophrenia spectrum disorders assessed by the Positive and Negative Syndrome Scale (PANSS); cannabis-users had to either have a diagnosis of cannabis use disorder or use cannabis at least twice a week. The main outcomes were the PANSS subscores extracted via the 3-factor (positive, negative and general) and 5-factor (positive, negative, disorganization, depression, excitement) structures. Preregistration is accessible via Prospero: ID CRD42022329172. Findings: Among the 1149 identified studies, 65 were eligible and 21 datasets were shared, totaling 3677 IPD and 3053 complete cases. The adjusted multivariate analysis revealed that relative to non-use, cannabis use was associated with higher severity of positive dimension (3-factor: Adjusted Mean Difference, aMD = 0.34, 95% Confidence Interval, CI = [0.03; 0.66]; 5-factor: aMD = 0.38, 95% CI = [0.08; 0.63]), lower severity of negative dimension (3-factor: aMD = -0.49, 95% CI [-0.90; -0.09]; 5-factor: aMD = -0.50, 95% CI = [-0.91; -0.08]), higher severity of excitement dimension (aMD = 0.16, 95% CI = [0.03; 0.28]). No association was found between cannabis use and disorganization (aMD = -0.13, 95% CI = [-0.42; 0.17]) or depression (aMD = -0.14, 95% CI = [-0.34; 0.06]). Interpretation: No causal relationship can be inferred from the current results. The findings could be in favor of both a detrimental and beneficial effect of cannabis on positive and negative symptoms, respectively. Longitudinal designs are needed to understand the role of cannabis is this association. The reported effect sizes are small and CIs are wide, the interpretation of findings should be taken with caution

Corrigendum to "Translating big data to better treatment in bipolar disorder - a manifesto for coordinated action [European Neuropsychopharmacology (2020) 36, 121-136]"

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Translating big data to better treatment in bipolar disorder - a manifesto for coordinated action

Bipolar disorder (BD) is a major healthcare and socio-economic challenge. Despite its substantial burden on society, the research activity in BD is much smaller than its economic impact appears to demand. There is a consensus that the accurate identification of the underlying pathophysiology for BD is fundamental to realize major health benefits through better treatment and preventive regimens. However, to achieve these goals requires coordinated action and innovative approaches to boost the discovery of the neurobiological underpinnings of BD, and rapid translation of research findings into development and testing of better and more specific treatments. To this end, we here propose that only a large-scale coordinated action can be successful in integrating international big-data approaches with real-world clinical interventions. This could be achieved through the creation of a Global Bipolar Disorder Foundation, which could bring government, industry and philanthropy together in common cause. A global initiative for BD research would come at a highly opportune time given the seminal advances promised for our understanding of the genetic and brain basis of the disease and the obvious areas of unmet clinical need. Such an endeavour would embrace the principles of open science and see the strong involvement of user groups and integration of dissemination and public involvement with the research programs. We believe the time is right for a step change in our approach to understanding, treating and even preventing BD effectively