Societal recovery trajectories in people with a psychotic disorder in long term care: a latent class growth analysis.

PURPOSE: For many individuals with a psychotic disorder societal recovery is not accomplished. Research on societal recovery trajectories is mostly focussed on patients with a first episode psychosis. The present study aims to identify distinct societal trajectories in those with long duration of illness, through the identification of patient subgroups that are characterized by homogeneous trajectories. METHODS: Longitudinal data were used from an ongoing dynamic cohort in which people with a psychotic disorder receive yearly measurements to perform a latent class growth analysis. Societal functioning was assessed with the Functional Recovery tool, consisting of three items (1) daily living and self-care, (2) work, study and housekeeping, and (3) social contacts. Furthermore, logistic regression was used to compare subgroups with similar societal recovery at baseline, but distinct trajectories. RESULTS: A total of 1476 people were included with a mean treatment time of 19 years (SD 10.1). Five trajectories of functioning were identified, a high stable (24.5%), a medium stable (28.3%), a low stable (12.7%), a high declining (11.2%) and a medium increasing subgroup (23.3%). Predictors for not deteriorating included happiness, recent hospitalisation, being physically active, middle or higher education and fewer negative symptoms. Predictors for improving included fewer positive and negative symptoms, fewer behavioural problems and fewer physical and cognitive impairments. CONCLUSION: While the majority of individuals show a stable trajectory over four years, there were more patients achieving societal recovery than patients deteriorating. Predictors for improvement are mainly related to symptoms and behavioural problems, while predictors for deteriorating are related to non-symptomatic aspects such as physical activity, happiness and level of education.

The bumpy road of trauma-focused treatment: Posttraumatic stress disorder symptom exacerbation in people with psychosis.

Concern for symptom exacerbation and treatment drop-out is an important barrier to the implementation of trauma-focused therapy (TFT), especially in people with a psychotic disorder. This study, which was part of a multicenter randomized controlled trial, investigated posttraumatic stress disorder (PTSD) symptom exacerbation during eye movement desensitization reprocessing (EMDR) therapy and prolonged exposure (PE) in a sample of 99 participants with PTSD and psychosis. Symptom exacerbations during the first four sessions (early exacerbation) and between-session exacerbations over the course of therapy were monitored using the PTSD Symptom Scale-Self Report. Analyses of covariance and chi-square tests were conducted to investigate exacerbation rates and their associations with treatment response and drop-out. Both early exacerbation and between-session exacerbation were relatively common (32.3% and 46.5%, respectively) but were unrelated to poor treatment response or an increased likelihood of treatment drop-out. Both clinicians and patients need to be aware that symptom exacerbation during TFT is common and not related to poor outcomes. Symptom exacerbation can be part of the therapeutic process, should be acknowledged and guided, and should not be a barrier to the implementation of TFT in people with psychosis.

Expression, sorting and transport studies for the orphan carrier SLC10A4 in neuronal and non-neuronal cell lines and in Xenopus laevis oocytes.

BACKGROUND: SLC10A4 belongs to the solute carrier family SLC10 whose founding members are the Na(+)/taurocholate co-transporting polypeptide (NTCP, SLC10A1) and the apical sodium-dependent bile acid transporter (ASBT, SLC10A2). These carriers maintain the enterohepatic circulation of bile acids between the liver and the gut. SLC10A4 was identified as a novel member of the SLC10 carrier family with the highest phylogenetic relationship to NTCP. The SLC10A4 protein was detected in synaptic vesicles of cholinergic and monoaminergic neurons of the peripheral and central nervous system, suggesting a transport function for any kind of neurotransmitter. Therefore, in the present study, we performed systematic transport screenings for SLC10A4 and also aimed to identify the vesicular sorting domain of the SLC10A4 protein. RESULTS: We detected a vesicle-like expression pattern of the SLC10A4 protein in the neuronal cell lines SH-SY5Y and CAD. Differentiation of these cells to the neuronal phenotype altered neither SLC10A4 gene expression nor its vesicular expression pattern. Functional transport studies with different neurotransmitters, bile acids and steroid sulfates were performed in SLC10A4-transfected HEK293 cells, SLC10A4-transfected CAD cells and in Xenopus laevis oocytes. For these studies, transport by the dopamine transporter DAT, the serotonin transporter SERT, the choline transporter CHT1, the vesicular monoamine transporter VMAT2, the organic cation transporter Oct1, and NTCP were used as positive control. SLC10A4 failed to show transport activity for dopamine, serotonin, norepinephrine, histamine, acetylcholine, choline, acetate, aspartate, glutamate, gamma-aminobutyric acid, pregnenolone sulfate, dehydroepiandrosterone sulfate, estrone-3-sulfate, and adenosine triphosphate, at least in the transport assays used. When the C-terminus of SLC10A4 was replaced by the homologous sequence of NTCP, the SLC10A4-NTCP chimeric protein revealed clear plasma membrane expression in CAD and HEK293 cells. But this chimera also did not show any transport activity, even when the N-terminal domain of SLC10A4 was deleted by mutagenesis. CONCLUSIONS: Although different kinds of assays were used to screen for transport function, SLC10A4 failed to show transport activity for a series of neurotransmitters and neuromodulators, indicating that SLC10A4 does not seem to represent a typical neurotransmitter transporter such as DAT, SERT, CHT1 or VMAT2.

Trauma-focused therapies for post-traumatic stress in psychosis: study protocol for the RE.PROCESS randomized controlled trial.

INTRODUCTION: Many people with psychotic disorders experience symptoms of post-traumatic stress disorder (PTSD). In recent years, several trauma-focused therapies (TFTs), including cognitive restructuring (CR), prolonged exposure (PE), and eye movement desensitization and reprocessing (EMDR) have been studied and found to be safe and effective in reducing PTSD symptoms in individuals with psychosis. However, studies were conducted in different countries, with varying inclusion criteria, therapy duration, control groups, and trial outcomes. RE.PROCESS will be the first study to compare the impact of CR, PE, and EMDR with a waiting list control condition within the same context. METHODS AND ANALYSIS: This is the protocol of a pragmatic, single-blind, multicentre, superiority randomized controlled trial, in which CR, PE, and EMDR are compared to a waiting list control condition for TFT (WL) in a naturalistic treatment setting. Inclusion criteria are as follows: age ≥ 16 years; meeting full DSM-5 diagnostic criteria for PTSD on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), with a total CAPS score ≥ 23; and a psychotic disorder in the schizophrenia spectrum confirmed by the Structured Clinical Interview for DSM-5 (SCID-5). Participants (N=200) will be randomly allocated to 16 sessions of one of the TFTs or WL, in addition to receiving treatment as usual (TAU) for psychosis. The primary objective is to compare the effects of CR, PE, and EMDR to WL on researcher-rated severity of PTSD symptoms over time from baseline to 6-month follow-up. Secondary objectives are to examine these effects at the separate time-points (i.e., mid-treatment, post-treatment, and at 6-month follow-up) and to test the effects for clinician-rated presence of PTSD diagnosis, and self-rated severity of (complex) PTSD symptoms. DISCUSSION: This is the first RCT to directly compare the effects of CR, PE, and EMDR within the same context to TAU on PTSD symptoms in individuals with psychosis and PTSD. Secondary effects on clinical and functional outcomes will be investigated both directly after therapy and long term. TRIAL REGISTRATION: ISRCTN ISRCTN56150327 . Registered 18 June 2019.

What Constitutes Sufficient Evidence for Case Formulation-Driven CBT for Psychosis? Cumulative Meta-analysis of the Effect on Hallucinations and Delusions.

OBJECTIVE: Following 2 decades of research on cognitive behavioral therapy for psychosis (CBTp), it is relevant to consider at which point the evidence base is considered sufficient. We completed a cumulative meta-analysis to assess the sufficiency and stability of the evidence base for hallucinations and delusions. METHOD: We updated the systematic search from our previous meta-analytic review from August 2013 until December 2019. We identified 20 new randomized controlled trials (RCTs) resulting in inclusion of 35 RCTs comparing CBTp with treatment-as-usual (TAU) or active controls (AC). We analyzed data from participants with psychosis (N = 2407) over 75 conventional meta-analytic comparisons. We completed cumulative meta-analyses (including fail-safe ratios) for key comparisons. Publication bias, heterogeneity, and risk of bias were examined. RESULTS: Cumulative meta-analyses demonstrated sufficiency and stability of evidence for hallucinations and delusions. The fail-safe ratio demonstrated that the evidence base was sufficient in 2016 for hallucinations and 2015 for delusions. In conventional meta-analyses, CBTp was superior for hallucinations (g = 0.34, P < .01) and delusions (g = 0.37, P < .01) when compared with any control. Compared with TAU, CBTp demonstrated superiority for hallucinations (g = 0.34, P < .01) and delusions (g = 0.37, P < .01). Compared with AC, CBT was superior for hallucinations (g = 0.34, P < .01), but not for delusions although this comparison was underpowered. Sensitivity analyses for case formulation, primary outcome focus, and risk of bias demonstrated increases in effect magnitude for hallucinations. CONCLUSIONS: The evidence base for the effect of CBTp on hallucinations and delusions demonstrates sufficiency and stability across comparisons, suggesting limited value of new trials evaluating generic CBTp.

Examining the effectiveness of a web-based intervention for symptoms of depression and anxiety in college students: study protocol of a randomised controlled trial.

INTRODUCTION: The college years are a peak period for the onset of common mental disorders. Poor mental health is associated with low academic attainment, physical, interpersonal and cognitive impairments. Universities can use online approaches to screen students for mental disorders and treat those in need. The present study aims to assess the effectiveness of a guided web-based transdiagnostic individually tailored intervention to treat students with symptoms of depression and/or anxiety. METHODS: and analysis : The present study is a randomised controlled trial. Participants are Dutch college students (≥18 years) with mild to moderate depression and/or anxiety symptoms. The intervention is a guided web-based transdiagnostic individually tailored intervention that targets symptoms of depression and/or anxiety. The intervention consists of seven online sessions with a duration ranging from 4 to 7 weeks depending on individual progress. A booster session is administered 4 weeks after the completion of the seventh session. Primary outcome measures are the Patient Health Questionnaire for depression and the Generalised Anxiety Disorder 7-item scale for anxiety. These scales are administered at screening, post-treatment and follow-up assessments (6 and 12 months post-randomisation). : E THICS AND DISSEMINATION: The Medical Ethics Committee of the Vrije Universiteit Medical Centre has approved the protocol (registration number 2016.583, A2017.362andA2018.421). Results of the trial will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NTR6797; Pre-results.

Do guided internet-based interventions result in clinically relevant changes for patients with depression? An individual participant data meta-analysis.

Little is known about clinically relevant changes in guided Internet-based interventions for depression. Moreover, methodological and power limitations preclude the identification of patients' groups that may benefit more from these interventions. This study aimed to investigate response rates, remission rates, and their moderators in randomized controlled trials (RCTs) comparing the effect of guided Internet-based interventions for adult depression to control groups using an individual patient data meta-analysis approach. Literature searches in PubMed, Embase, PsycINFO and Cochrane Library resulted in 13,384 abstracts from database inception to January 1, 2016. Twenty-four RCTs (4889 participants) comparing a guided Internet-based intervention with a control group contributed data to the analysis. Missing data were multiply imputed. To examine treatment outcome on response and remission, mixed-effects models with participants nested within studies were used. Response and remission rates were calculated using the Reliable Change Index. The intervention group obtained significantly higher response rates (OR = 2.49, 95% CI 2.17-2.85) and remission rates compared to controls (OR = 2.41, 95% CI 2.07-2.79). The moderator analysis indicated that older participants (OR = 1.01) and native-born participants (1.66) were more likely to respond to treatment compared to younger participants and ethnic minorities respectively. Age (OR = 1.01) and ethnicity (1.73) also moderated the effects of treatment on remission.Moreover, adults with more severe depressive symptoms at baseline were more likely to remit after receiving internet-based treatment (OR = 1.19). Guided Internet-based interventions lead to substantial positive treatment effects on treatment response and remission at post-treatment. Thus, such interventions may complement existing services for depression and potentially reduce the gap between the need and provision of evidence-based treatments.