Accelerating the development of a psychological intervention to restore treatment decision-making capacity in patients with schizophrenia-spectrum disorder: a study protocol for a multi-site, assessor-blinded, pilot Umbrella trial (the DEC:IDES trial).

BACKGROUND: A high proportion of patients diagnosed with schizophrenia-spectrum disorders will at some point in their lives be assessed as not having the capacity to make their own decisions about pharmacological treatment or inpatient care ('capacity'). Few will be helped to regain it before these interventions proceed. This is partly because effective and safe methods to do so are lacking. Our aim is to accelerate their development by testing, for the first time in mental healthcare, the feasibility, acceptability and safety of running an 'Umbrella' trial. This involves running, concurrently and under one multi-site infrastructure, multiple assessor-blind randomised controlled trials, each of which is designed to examine the effect on capacity of improving a single psychological mechanism ('mechanism'). Our primary objectives are to demonstrate feasibility of (i) recruitment and (ii) data retention on the MacArthur Competence Assessment Tool-Treatment (MacCAT-T; planned primary outcome for a future trial) at end-of-treatment. We selected three mechanisms to test: 'self-stigma', low self-esteem and the 'jumping to conclusions' bias. Each is highly prevalent in psychosis, responsive to psychological intervention, and hypothesised to contribute to impaired capacity. METHODS: Sixty participants with schizophrenia-spectrum diagnoses, impaired capacity and one or more mechanism(s) will be recruited from outpatient and inpatient mental health services in three UK sites (Lothian, Scotland; Lancashire and Pennine; North West England). Those lacking capacity to consent to research could take part if the key criteria were met, including either proxy consent (Scotland) or favourable Consultee advice (England). They will be allocated to one of three randomised controlled trials, depending on which mechanism(s) they have. They will then be randomised to receive, over an 8-week period and in addition to treatment as usual (TAU), 6 sessions of either a psychological intervention which targets the mechanism, or 6 sessions of assessment of the causes of their incapacity (control condition). Participants are assessed at 0 (baseline), 8 (end-of-treatment) and 24 (follow-up) weeks post-randomisation using measures of capacity (MacCAT-T), mechanism, adverse events, psychotic symptoms, subjective recovery, quality of life, service use, anxiety, core schemata and depression. Two nested qualitative studies will be conducted; one to understand participant and clinician experiences and one to investigate the validity of MacCAT-T appreciation ratings. DISCUSSION: This will be the first Umbrella trial in mental healthcare. It will produce the first 3 single-blind randomised controlled trials of psychological interventions to support treatment decision-making in schizophrenia-spectrum disorder. Demonstrating feasibility will have significant implications not only for those seeking to support capacity in psychosis, but also for those who wish to accelerate the development of psychological interventions for other conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04309435 . Pre-registered on 16 March 2020.

Impaired verbal memory function is related to anterior cingulate glutamate levels in schizophrenia: findings from the STRATA study.

Impaired cognition is associated with lower quality of life and poor outcomes in schizophrenia. Brain glutamate may contribute to both clinical outcomes and cognition, but these relationships are not well-understood. We studied a multicentre cohort of 85 participants with non-affective psychosis using proton magnetic resonance spectroscopy. Glutamate neurometabolites were measured in the anterior cingulate cortex (ACC). Cognition was assessed using the Brief Assessment for Cognition in Schizophrenia (BACS). Patients were categorised as antipsychotic responders or non-responders based on treatment history and current symptom severity. Inverted U-shaped associations between glutamate or Glx (glutamate + glutamine) with BACS subscale and total scores were examined with regression analyses. We then tested for an interaction effect of the antipsychotic response group on the relationship between glutamate and cognition. ACC glutamate and Glx had a positive linear association with verbal memory after adjusting for age, sex and chlorpromazine equivalent dose (glutamate, ß = 3.73, 95% CI = 1.26-6.20, P = 0.004; Glx, ß = 3.38, 95% CI = 0.84-5.91, P = 0.01). This association did not differ between good and poor antipsychotic response groups. ACC glutamate was also positively associated with total BACS score (ß = 3.12, 95% CI = 0.01-6.23, P = 0.046), but this was not significant after controlling for antipsychotic dose. Lower glutamatergic metabolites in the ACC were associated with worse verbal memory, and this relationship was independent of antipsychotic response. Further research on relationships between glutamate and cognition in antipsychotic responsive and non-responsive illness could aid the stratification of patient groups for targeted treatment interventions.

Metacognitive training modified for negative symptoms: A feasibility study.

OBJECTIVE: Although patients often prioritize the treatment of negative symptoms, few psychological interventions targeting negative symptoms exist. This study attempts to fill this gap by piloting a modified metacognitive training programme, specifically targeted at negative symptoms (MCT-N), with a group of patients with prominent negative symptoms. METHOD: We adopted a mixed methods case series design, providing detailed quantitative data on changes over time, to focus on potential mechanisms underlying the intervention, in combination with qualitative interviews. RESULTS: The intervention showed good feasibility as demonstrated by the attendance rate, the positive feedback from participants and the multidisciplinary team, and the improvements on negative symptoms observed following the intervention. Multilevel modelling showed that depression, internalized stigma and reflective functioning explained the variance in negative symptoms. DISCUSSION: The pilot study indicated that the intervention has high feasibility and that improvements in negative symptoms can be partially explained by improvements on depression, stigma and reflective functioning.

Unpacking stigma: Meta-analyses of correlates and moderators of personal stigma in psychosis.

Personal stigma entails perceived, experienced and internalised stigmatisation. Mental Health stigma has been widely researched across a range of countries and a meta-analysis of their associations and moderators in psychosis is timely. Meta-analyses were conducted examining the correlates and moderators of personal stigma in terms of: (1) demographic variables (2) illness related variables (3) symptoms/negative outcomes, and (4) aspects of wellbeing. Associations were obtained from a total of 216 records. Several demographic factors including age, economic status, employment, and rural residence had small associations with aspects of personal stigma (r's = 0.12 to -0.13). Personal stigma aspects were inversely related to medication adherence (r's = -0.20, -0.21), and positively associated with insight and number of hospitalisations (r's = 0.09-0.19). Most symptoms were positively associated with personal stigma (r's = 0.10-0.43), whereas inverse relations with wellbeing variables were identified (r's = -0.13 to -0.54). Moderator effects emerged including that of cultural setting and sex, age and education level, highlighting the role of cultural and demographic factors in shaping personal stigma aspects in psychosis. The present study also highlights the importance of recognizing the negative effect of actual stigma and discrimination experiences; particularly its detrimental impact on self-image and its complex role in shaping the internalisation of societal stigma.

Dopamine and Glutamate in Antipsychotic-Responsive Compared With Antipsychotic-Nonresponsive Psychosis: A Multicenter Positron Emission Tomography and Magnetic Resonance Spectroscopy Study (STRATA).

The variability in the response to antipsychotic medication in schizophrenia may reflect between-patient differences in neurobiology. Recent cross-sectional neuroimaging studies suggest that a poorer therapeutic response is associated with relatively normal striatal dopamine synthesis capacity but elevated anterior cingulate cortex (ACC) glutamate levels. We sought to test whether these measures can differentiate patients with psychosis who are antipsychotic responsive from those who are antipsychotic nonresponsive in a multicenter cross-sectional study. 1H-magnetic resonance spectroscopy (1H-MRS) was used to measure glutamate levels (Glucorr) in the ACC and in the right striatum in 92 patients across 4 sites (48 responders [R] and 44 nonresponders [NR]). In 54 patients at 2 sites (25 R and 29 NR), we additionally acquired 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine (18F-DOPA) positron emission tomography (PET) to index striatal dopamine function (Kicer, min-1). The mean ACC Glucorr was higher in the NR than the R group after adjustment for age and sex (F1,80 = 4.27; P = .04). This was associated with an area under the curve for the group discrimination of 0.59. There were no group differences in striatal dopamine function or striatal Glucorr. The results provide partial further support for a role of ACC glutamate, but not striatal dopamine synthesis, in determining the nature of the response to antipsychotic medication. The low discriminative accuracy might be improved in groups with greater clinical separation or increased in future studies that focus on the antipsychotic response at an earlier stage of the disorder and integrate other candidate predictive biomarkers. Greater harmonization of multicenter PET and 1H-MRS may also improve sensitivity.

Efficacy of Mentalization-based group therapy for adolescents: the results of a pilot randomised controlled trial.

BACKGROUND: Mentalization Based Therapy (MBT) has yielded promising outcomes for reducing self-harm, although to date only one study has reported MBT's effectiveness for adolescents (Rossouw and Fonagy, J Am Acad Child Adolesc Psychiatry 51:1304-1313, 2012) wherein the treatment protocol consisted of an intensive programme of individual and family therapy. We sought to investigate an adaptation of the adult MBT introductory manual in a group format for adolescents. METHODS: The present study is a randomised controlled single blind feasibility trial that aims to (1) adapt the original explicit MBT introductory group manual for an adolescent population (MBT-Ai) and to (2) assess the feasibility of a trial of MBT-Ai through examination of consent rates, attendance, attrition and self-harm. Repeated measures ANOVAs were conducted to examine change over time in independent and dependent variables between groups, and multi level models (MLM) were conducted to examine key predictors in relation to change over time with self-report self-harm and emergency department presentation for harm as the primary outcome variables. RESULTS: Fifty-three young people consented to participate and were randomised to MBT-Ai + TAU or TAU alone. Five participants withdrew from the trial. Trial procedures seemed appropriate and safe, with acceptable group attendance. Self-reported self-harm and emergency department presentation for self-harm significantly decreased over time in both groups, though there were no between group differences. Social anxiety, emotion regulation, and borderline traits also significantly decreased over time in both groups. Mentalization emerged as a significant predictor of change over time in self reported self harm and hospital presentation for self-harm. CONCLUSIONS: It was feasible to carry out an RCT of MBT-Ai for adolescents already attending NHS CAMHS who have recently self-harmed. Our data gave signals that suggested a relatively brief group-based MBT-Ai intervention may be a promising intervention with potential for service implementation. Future research should consider the appropriate format, dosage and intensity of MBT for the adolescent population. TRIAL REGISTRATION: NCT02771691 ; Trial Registration Date: 25/04/2016.

[Renal transplantation in patients with lupus nephritis]. / Transplantacija bubrega u bolesnika s lupusnim nefritisom.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), associated with high morbidity and mortality. Up to 60% of SLE patients develop LN, and despite novel and potent therapeutic regimens, 5 to 22% develop end-stage renal disease within 15 years of diagnosis. While LN primarily affects younger individuals, it is important to choose optimal method of renal replacement therapy for those who develop end-stage renal disease. Numerous studies were carried out trying to solve problems of treatment of patients with LN. Increased risk of infections, disease recurrence in renal allograft, undefined criteria for follow-up of disease activity after transplantation, as well as higher inci- dence of rejection episodes and thrombotic events are well known risks which have postponed and restricted access to transplantation for patients with LN for long-time. However, numerous studies have demonstrated similar long-term survival in patients treated with haemodialysis or peritoneal dialysis, with clear superiority of renal transplantation regarding the prolonged survival and better quality of life for SLE patients. Many questions are still waiting for answers. Close cooperation between nephrologists and immunologists provides the best treatment for SLE patients with end-stage renal disease.