Daily-life stress reactivity and recovery following virtual-reality-based cognitive behavioral therapy in patients with a psychotic disorder.

Introduction: Studies have consistently demonstrated increased stress sensitivity in individuals with psychosis. Since stress sensitivity may play a role in the onset and maintenance of psychosis, this could potentially be a promising target for treatment. The current study was the first to investigate whether reactivity to and recovery from daily-life stressors in psychosis change in response to treatment, namely virtual-reality-based cognitive behavioral therapy (VR-CBT). Methods: 116 patients were randomized to either VR-CBT or the waiting list control group (WL). Pre-treatment and post-treatment participants completed a diary ten times a day during six to ten days. Multilevel analyses were used to model the time-lagged effects of daily stressful events on negative affect (NA) and paranoia symptoms to examine reactivity and recovery. Results: There was a significant difference in NA reactivity. VR-CBT showed higher NA at post-treatment compared to pre-treatment than WL (bpre=0.14; bpost=0.19 vs bpre=0.18; bpost=0.14). There was a significant difference in NA recovery and paranoia recovery between the groups at lag 1: VR-CBT showed relatively lower negative affect (bpre=0.07; bpost=-0.06) and paranoia (bpre= 0.08; bpost=-0.10) at post-treatment compared to pre-treatment than WL (bpre=0.08; bpost=0.08; bpre=0.04; bpost=0.03). Conclusion: Negative affect and paranoia recovery improved in response to treatment. Increased NA reactivity may be explained by a decrease in safety behavior in the VR-CBT group. The discrepancy between reactivity and recovery findings may be explained by the inhibitory learning theory that suggests that an original threat reaction may not erase but can be inhibited as a consequence of exposure therapy.

The effectiveness and safety of dialectical behavior therapy for suicidal ideation and behavior in autistic adults: a pragmatic randomized controlled trial.

BACKGROUNDS: Many autistic people in mental health are suicidal. This study evaluated the effectiveness of dialectical behavior therapy (DBT) v. treatment as usual (TAU) in reducing suicidal ideation and suicide attempts. METHODS: At six Dutch mental health centers, 123 outpatients (18-65 years) with DSM-5 diagnosed autism spectrum disorder (ASD) and suicidal behavior were randomly assigned to the DBT intervention group (n = 63) or TAU control group (n = 60). Assessments were conducted at baseline, post-treatment at 6 months and 12-month follow-up. The primary outcomes were severity of suicidal ideation and frequency of suicide attempts. The severity of depression and social anxiety were secondary outcomes. RESULTS: At end-of-treatment, DBT significantly reduced both suicidal ideation (z = -2.24; p = 0.025; b = -4.41; s.e. = 197.0) and suicide attempts (z = -3.15; p = 0.002; IRR = 0.046; s.e. = 0.045) compared to TAU, but lost statistical significance at the 12-month follow-up. Depression severity significantly decreased with DBT (z = -1.99; p = 0.046: b = -2.74; s.e. = 1.37) remaining so at 12 months (z = -2.46; p = 0.014; b = -3.37; s.e. = 1.37). No effects were observed on social anxiety. Severe adverse events included two suicides in the TAU condition. CONCLUSIONS: DBT is an acceptable, safe, and short-term effective intervention to reduce suicidal ideation and suicide attempts in autistic adults with suicidal behavior.

Effects on voice hearing distress and social functioning of unguided application of a smartphone app - A randomized controlled trial.

Background: Temstem is a smartphone app developed with and for clinical voice hearing individuals with the aim to reduce their voice hearing distress and improve social functioning. Methods: A randomized controlled trial with adult outpatients suffering from distressing and frequent auditory verbal hallucinations (AVH) was conducted. Participants were randomized to unguided 'Temstem+AVH monitoring' or unguided 'AVH monitoring only' (control condition). Assessments were performed at baseline, post-intervention (week 5-6), and follow-up (week 9-10). Primary outcomes were voice hearing distress and social functioning, as measured with Experience Sampling Method (ESM), consisting of multiple daily questionnaires during six days. In addition, voices and mood were self-monitored with help of a daily reflective questionnaire. Analyses were linear regression models (intention-to-treat). Results: 44 Participants were allocated to Temstem and 45 to the control condition. No significant differences between the groups were found on both primary outcomes. Conclusion: Our results do not support the effectiveness of stand-alone use of Temstem versus symptom monitoring on voice hearing distress or social functioning in voice hearing individuals. In order to potentially improve effectiveness of an mHealth tool in a population of people with frequent and distressing voices, we recommend to involve persons with lived experience in all stages of development and research; to thoroughly test the (technological) usability before performing an RCT; to test whether guidance of a therapist is needed to optimize effectiveness; and to provide prompts to remind the user to actually use the tool.

The temporal association between social isolation, distress, and psychotic experiences in individuals at clinical high-risk for psychosis.

BACKGROUND: Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis. METHODS: We used experience sampling methodology in a sample of 137 CHR participants. We analyzed the association between SI, PEs, and distress using time-lagged linear mixed-effects models. RESULTS: SI did not predict next-moment fluctuations in PEs, or vice versa. Furthermore, although SI-related distress was not predictive of subsequent PEs, general affective distress during SI was a robust predictor of next-moment PEs. CONCLUSIONS: Our results suggest that SI and PEs are not directly related on a moment-to-moment level, but a negative emotional state when alone does contribute to the risk of PEs. These findings highlight the role of affective wellbeing during early-stage psychosis development.

Psychotic-like experiences and multimorbid psychopathology: The relationship between the 16-item prodromal questionnaire and DSM-IV classifications in a help-seeking population.

AIM: Identifying multimorbid psychopathology is necessary to offer more adequate treatment and ultimately reduce the prevalence of persistent mental illnesses. Psychotic symptoms are increasingly seen as a transdiagnostic indicator of multimorbidity, severity and complexity of non-psychotic psychopathology. This study aims to investigate whether psychotic-like experiences and subclinical psychotic symptoms as measured by the 16-item Prodromal Questionnaire are also associated with multimorbid psychopathology. METHODS: Participants were help-seeking individuals from outpatient mental healthcare settings and intensive home-treatment teams, aged 17-35. Assessment included the 16-item Prodromal Questionnaire to measure psychotic-like experiences, the Structured Clinical Interview for DSM-IV Axis I, and three sections of the Structured Clinical Interview for DSM-IV Axis II Disorders to determine DSM-IV-TR classifications. The final sample comprised of 160 participants who scored above a cutoff of 6 items on the 16-item Prodromal Questionnaire (HIGH-score) and 60 participants who scored below cutoff (LOW-score). A Poisson Regression was executed to determine the association between the PQ-16 and DSM-IV-TR classifications. RESULTS: The HIGH-score group had a mean of 2.76 multimorbid disorders (range 0-7), while the LOW-score group had a mean of 1.45 disorders (range 0-3). Participants with four to seven disorders scored high on the 16-item Prodromal Questionnaire. CONCLUSIONS: Our results suggest that psychotic-like experiences are associated with multimorbidity and severity of psychopathology. Screening for psychotic-like experiences via the PQ-16 in a help-seeking population may help prevent under-diagnosis and under-treatment of comorbid psychopathology.

The Prevalence of Suicidal Behavior in Autism Spectrum Disorder.

Background: Suicidal ideation (SI) and suicide attempts (SA) are common in autistic individuals, but prevalence rates have not yet been estimated with meta-analysis. Aims: This meta-analysis aims to estimate SI and SA prevalence rates in autistic individuals and identify subgroup differences based on sample characteristics and study quality. Methods: A systematic search identified 52 studies with 88,509 autistic participants reporting SI and SA. Pooled prevalence estimates were calculated using a random-effects model. Results: Pooled prevalence estimates of lifetime SI and SA were 37.2% [95% CI 25.3-50.8] and 15.3% [95% CI 9.5-23.6], respectively. For 12-month prevalence, this was 25.4% [95% CI 19.0-33.2] and 14.1% [95% CI 7.4-25.2], respectively. Subgroup analyses revealed significant differences based on age (SI), region (SI), data collection (SI), measurement scales used to define autism and suicidality (SA), and representation of the study sample (SI and SA). Heterogeneity measures were high for all outcomes (I2 = 60.3-99.1%). Limitations: The heterogeneity of the included studies may limit the generalizability of our findings. Conclusion: The high rates of suicidal problems in autistic individuals call for a systematic evaluation of suicidality in clinical practice and adequate therapeutic interventions to improve this condition.

Transdiagnostic Ecological Momentary Intervention for Improving Self-Esteem in Youth Exposed to Childhood Adversity: The SELFIE Randomized Clinical Trial.

Importance: Targeting low self-esteem in youth exposed to childhood adversity is a promising strategy for preventing adult mental disorders. Ecological momentary interventions (EMIs) allow for the delivery of youth-friendly, adaptive interventions for improving self-esteem, but robust trial-based evidence is pending. Objective: To examine the efficacy of SELFIE, a novel transdiagnostic, blended EMI for improving self-esteem plus care as usual (CAU) compared with CAU only. Design, Setting, and Participants: This was a 2-arm, parallel-group, assessor-blinded, randomized clinical trial conducted from December 2018 to December 2022. The study took place at Dutch secondary mental health services and within the general population and included youth (aged 12-26 years) with low self-esteem (Rosenberg Self-Esteem Scale [RSES] <26) exposed to childhood adversity. Interventions: A novel blended EMI (3 face-to-face sessions, email contacts, app-based, adaptive EMI) plus CAU or CAU only. Main Outcomes and Measures: The primary outcome was RSES self-esteem at postintervention and 6-month follow-up. Secondary outcomes included positive and negative self-esteem, schematic self-beliefs, momentary self-esteem and affect, general psychopathology, quality of life, observer-rated symptoms, and functioning. Results: A total of 174 participants (mean [SD] age, 20.7 [3.1] years; 154 female [89%]) were included in the intention-to-treat sample, who were primarily exposed to childhood emotional abuse or neglect, verbal or indirect bullying, and/or parental conflict. At postintervention, 153 participants (87.9%) and, at follow-up, 140 participants (80.5%), provided primary outcome data. RSES self-esteem was, on average, higher in the experimental condition (blended EMI + CAU) than in the control condition (CAU) across both postintervention and follow-up as a primary outcome (B = 2.32; 95% CI, 1.14-3.50; P < .001; Cohen d-type effect size [hereafter, Cohen d] = 0.54). Small to moderate effect sizes were observed suggestive of beneficial effects on positive (B = 3.85; 95% CI, 1.83-5.88; P < .001; Cohen d = 0.53) and negative (B = -3.78; 95% CI, -6.59 to -0.98; P = .008; Cohen d = -0.38) self-esteem, positive (B = 1.58; 95% CI, 0.41-2.75; P = .008; Cohen d = 0.38) and negative (B = -1.71; 95% CI, -2.93 to -0.48; P = .006; Cohen d = -0.39) schematic self-beliefs, momentary self-esteem (B = 0.29; 95% CI, 0.01-0.57; P = .04; Cohen d = 0.24), momentary positive affect (B = 0.23; 95% CI, 0.01-0.45; P = .04; Cohen d = 0.20), momentary negative affect (B = -0.33; 95% CI, -0.59 to -0.03, P = .01, Cohen d = -0.27), general psychopathology (B = -17.62; 95% CI, -33.03 to -2.21; P = .03; Cohen d = -0.34), and quality of life (B = 1.16; 95% CI, 0.18-2.13; P = .02; Cohen d = 0.33) across postintervention and follow-up. No beneficial effects on symptoms and functioning were observed. Conclusions and Relevance: A transdiagnostic, blended EMI demonstrated efficacy on the primary outcome of self-esteem and signaled beneficial effects on several secondary outcomes. Further work should focus on implementing this novel EMI in routine public mental health provision. Trial Registration: Dutch Trial Register Identifier:NL7129(NTR7475).

Testing the combination of Feeling Safe and peer counselling against formulation-based cognitive behaviour therapy to promote psychological wellbeing in people with persecutory delusions: study protocol for a randomized controlled trial (the Feeling Safe-NL Trial).

BACKGROUND: Persecutory delusions are strong threat beliefs about others' negative intentions. They can have a major impact on patients' day-to-day life. The Feeling Safe Programme is a new translational cognitive-behaviour therapy that helps patients modify threat beliefs and relearn safety by targeting key psychological causal factors. A different intervention approach, with growing international interest, is peer counselling to facilitate personal recovery. Combining these two approaches is a potential avenue to maximize patient outcomes. This combination of two different treatments will be tested as the Feeling Safe-NL Programme, which aims to promote psychological wellbeing. We will test whether Feeling Safe-NL is more effective and more cost-effective in improving mental wellbeing and reducing persecutory delusions than the current guideline intervention of formulation-based CBT for psychosis (CBTp). METHODS: A single-blind parallel-group randomized controlled trial for 190 out-patients who experience persecutory delusions and low mental wellbeing. Patients will be randomized (1:1) to Feeling Safe-NL (Feeling Safe and peer counselling) or to formulation-based CBTp, both provided over a period of 6 months. Participants in both conditions are offered the possibility to self-monitor their recovery process. Blinded assessments will be conducted at 0, 6 (post-treatment), 12, and 18 months. The primary outcome is mental wellbeing. The overall effect over time (baseline to 18-month follow-up) and the effects at each timepoint will be determined. Secondary outcomes include the severity of the persecutory delusion, general paranoid ideation, patient-chosen therapy outcomes, and activity. Service use data and quality of life data will be collected for the health-economic evaluation. DISCUSSION: The Feeling Safe-NL Trial is the first to evaluate a treatment for people with persecutory delusions, while using mental wellbeing as the primary outcome. It will also provide the first evaluation of the combination of a peer counselling intervention and a CBT-based program for recovery from persecutory delusions. TRIAL REGISTRATION: Current Controlled Trials ISRCTN25766661 (retrospectively registered 7 July 2022).

Effects of an eating club for people with a psychotic disorder on personal recovery: Results of a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Many people with a psychotic disorder are coping with severe psychosocial limitations related to their illness. The current randomized controlled trial (RCT) investigates the effects of an eating club intervention (HospitalitY (HY)) aimed to improve personal and societal recovery. METHODS: In 15 biweekly sessions participants received individual home-based skill training and guided peer support sessions in groups of three participants from a trained nurse. A multi-center RCT was conducted (intended sample size: n = 84; n = 7 per block) in patients with a diagnosis of schizophrenia spectrum receiving community treatment. HospitalitY was compared to a Waiting List Control (WLC) condition at three time points (baseline, end-of-treatment (8 months) and follow-up (12 months)) using personal recovery as primary outcome and loneliness, social support, self-stigma, self-esteem, social skills, (social) functioning, independency competence, and psychopathology as secondary outcomes. Outcomes were evaluated with a mixed modeling statistical procedure. RESULTS: The HY-intervention had no significant effects on personal recovery or secondary outcomes. More attendance was associated with higher scores on social functioning. LIMITATIONS: With N = 43 participants included, power was insufficient. Seven HY-groups were started, from which three discontinued before the sixth meeting, one HY group stopped due the start of the COVID-19 pandemic. CONCLUSIONS: Despite a promising pilot study on feasibility, the current RCT did not show any effects of the HY intervention. A mixed qualitative-quantitative research methods might be more appropriate for researching the HospitalitY-intervention to investigate what social and cognitive processes are at play in this peer guided social intervention.

Influence of cannabis use on incidence of psychosis in people at clinical high risk.

AIMS: Evidence for case-control studies suggests that cannabis use is a risk factor for the development of psychosis. However, there have been limited prospective studies and the direction of this association remains controversial. The primary aim of the present study was to examine the association between cannabis use and the incidence of psychotic disorders in people at clinical high risk of psychosis. Secondary aims were to assess associations between cannabis use and the persistence of psychotic symptoms, and with functional outcome. METHODS: Current and previous cannabis use were assessed in individuals at clinical high risk of psychosis (n = 334) and healthy controls (n = 67), using a modified version of the Cannabis Experience Questionnaire. Participants were assessed at baseline and followed up for 2 years. Transition to psychosis and persistence of psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental States criteria. Level of functioning at follow up was assessed using the Global Assessment of Functioning disability scale. RESULTS: During follow up, 16.2% of the clinical high-risk sample developed psychosis. Of those who did not become psychotic, 51.4% had persistent symptoms and 48.6% were in remission. There was no significant association between any measure of cannabis use at baseline and either transition to psychosis, the persistence of symptoms, or functional outcome. CONCLUSIONS: These findings contrast with epidemiological data that suggest that cannabis use increases the risk of psychotic disorder.

Serum immune markers and transition to psychosis in individuals at clinical high risk.

Individuals at clinical high risk (CHR) for psychosis have been found to have altered cytokine levels, but whether these changes are related to clinical outcomes remains unclear. We addressed this issue by measuring serum levels of 20 immune markers in 325 participants (n = 269 CHR, n = 56 healthy controls) using multiplex immunoassays, and then followed up the CHR sample to determine their clinical outcomes. Among 269 CHR individuals, 50 (18.6 %) developed psychosis by two years. Univariate and machine learning techniques were used to compare levels of inflammatory markers in CHR subjects and healthy controls, and in CHR subjects who had (CHR-t), or had not (CHR-nt) transitioned to psychosis. An ANCOVA identified significant group differences (CHR-t, CHR-nt and controls) and post-hoc tests indicated that VEGF levels and the IL-10/IL-6 ratio were significantly higher in CHR-t than CHR-nt, after adjusting for multiple comparisons. Using a penalised logistic regression classifier, CHR participants were distinguished from controls with an area-under the curve (AUC) of 0.82, with IL-6 and IL-4 levels the most important discriminating features. Transition to psychosis was predicted with an AUC of 0.57, with higher VEGF level and IL-10/IL-6 ratio the most important discriminating features. These data suggest that alterations in the levels of peripheral immune markers are associated with the subsequent onset of psychosis. The association with increased VEGF levels could reflect altered blood-brain-barrier (BBB) permeability, while the link with an elevated IL-10/IL-6 ratio points to an imbalance between anti- and pro-inflammatory cytokines.

Impact of adverse childhood experiences on educational achievements in young people at clinical high risk of developing psychosis.

BACKGROUND: Adverse childhood experiences (ACE) can affect educational attainments, but little is known about their impact on educational achievements in people at clinical high risk of psychosis (CHR). METHODS: In total, 344 CHR individuals and 67 healthy controls (HC) were recruited as part of the European Community's Seventh Framework Programme-funded multicenter study the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI). The brief version of the Child Trauma Questionnaire was used to measure ACE, while educational attainments were assessed using a semi-structured interview. RESULTS: At baseline, compared with HC, the CHR group spent less time in education and had higher rates of ACE, lower rates of employment, and lower estimated intelligence quotient (IQ). Across both groups, the total number of ACE was associated with fewer days in education and lower level of education. Emotional abuse was associated with fewer days in education in HC. Emotional neglect was associated with a lower level of education in CHR, while sexual abuse was associated with a lower level of education in HC. In the CHR group, the total number of ACE, physical abuse, and neglect was significantly associated with unemployment, while emotional neglect was associated with employment. CONCLUSIONS: ACE are strongly associated with developmental outcomes such as educational achievement. Early intervention for psychosis programs should aim at integrating specific interventions to support young CHR people in their educational and vocational recovery. More generally, public health and social interventions focused on the prevention of ACE (or reduce their impact if ACE occur) are recommended.

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.

Speech Illusions in People at Clinical High Risk for Psychosis Linked to Clinical Outcome.

BACKGROUND AND HYPOTHESIS: Around 20% of people at clinical high risk (CHR) for psychosis later develop a psychotic disorder, but it is difficult to predict who this will be. We assessed the incidence of hearing speech (termed speech illusions [SIs]) in noise in CHR participants and examined whether this was associated with adverse clinical outcomes. STUDY DESIGN: At baseline, 344 CHR participants and 67 healthy controls were presented with a computerized white noise task and asked whether they heard speech, and whether speech was neutral, affective, or whether they were uncertain about its valence. After 2 years, we assessed whether participants transitioned to psychosis, or remitted from the CHR state, and their functioning. STUDY RESULTS: CHR participants had a lower sensitivity to the task. Logistic regression revealed that a bias towards hearing targets in stimuli was associated with remission status (OR = 0.21, P = 042). Conversely, hearing SIs with uncertain valence at baseline was associated with reduced likelihood of remission (OR = 7.72. P = .007). When we assessed only participants who did not take antipsychotic medication at baseline, the association between hearing SIs with uncertain valence at baseline and remission likelihood remained (OR = 7.61, P = .043) and this variable was additionally associated with a greater likelihood of transition to psychosis (OR = 5.34, P = .029). CONCLUSIONS: In CHR individuals, a tendency to hear speech in noise, and uncertainty about the affective valence of this speech, is associated with adverse outcomes. This task could be used in a battery of cognitive markers to stratify CHR participants according to subsequent outcomes.

Voice phenomenology as a mirror of the past.

BACKGROUND: Post-traumatic mechanisms are theorised to contribute to voice-hearing in people with psychosis and a history of trauma. Phenomenological links between trauma and voices support this hypothesis, as they suggest post-traumatic processes contribute to the content of, and relationships with, voices. However, research has included small samples and lacked theory-based comprehensive assessments. METHOD: In people with distressing voices (n = 73) who experienced trauma prior to voice-hearing, trauma-voice links were assessed both independently and dependently (descriptions were presented and rated separately and together, respectively) by both participants and researchers. A structured coding frame assessed four types of independent links (i.e. victimisation type, physiological-behavioural, emotional, and cognitive response themes including negative self-beliefs) and three types of dependent links: relational (similar interaction with/response to, voice and trauma); content (voice and trauma content are exactly the same); and identity (voice identity is the same as perpetrator). RESULTS: Independent links were prevalent in participants (51-58%) and low to moderately present in researcher ratings (8-41%) for significant themes. Identification of negative self-beliefs in trauma was associated with a significantly higher likelihood of negative self-beliefs in voices [participants odds ratio (OR) 9.8; researchers OR 4.9]. Participants and researchers also reported many dependent links (80%, 66%, respectively), most frequently relational links (75%, 64%), followed by content (60%, 25%) and identity links (51%, 22%). CONCLUSION: Trauma appears to be a strong shaping force for voice content and its psychological impact. The most common trauma-voice links involved the experience of cognitive-affective psychological threat, embodied in relational experiences. Trauma-induced mechanisms may be important intervention targets.

Cost-Effectiveness of Positive Memory Training (PoMeT) for the Treatment of Depression in Schizophrenia.

The Positive Memory Training (PoMeT) trial demonstrated reduced depression symptoms at 3 months for schizophrenia, but its longer-term outcome and cost impacts remain unknown. This study is a within-trial cost-utility analysis with quality-adjusted life years (QALYs) as outcome based on health-related quality of life (HRQoL) measurement and secondary outcome analyses of capability well-being. The incremental cost-effectiveness of PoMeT was compared to Treatment As Usual only (TAU) over 9 months from the 'health and social' care and 'societal' perspectives. Uncertainty was explored using bootstrapping and sensitivity analyses for cost outliers and outcome methods. HRQoL improvement was observed for both PoMeT and TAU at 3 months, but reached statistical significance and was sustained only for TAU. There was no change in capability well-being and no significant group difference in QALYs gained over 9 months. Mean intervention cost was GBP 823. Compared to TAU, PoMeT had significantly higher mental health care costs (+GBP 1251, 95% CI GBP 185 to GBP 2316) during the trial, but 'health and social care' and 'societal' cost differences were non-significant. Compared to the before-trial period, psychiatric medication costs increased significantly in both groups. The probability of PoMeT being cost-effective in the given format over 9 months was <30% and decreased further in sensitivity analyses.. Generalizability remains limited since the before-after cost analysis revealed additional treatment effects also in the TAU group that likely diminished the incremental impacts and cost-effectiveness of PoMeT. It is not clear whether an active post-intervention follow-up could result in sustained longer-term effects and improved cost-effectiveness.

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.

Momentary effects of Temstem, an app for voice-hearing individuals: Results from naturalistic data from 1048 users.

Background: Temstem is a mobile application developed in cooperation with voice-hearing persons to help them cope with distressing voices. After psychoeducation about voice hearing, Temstem offers two functions: Silencing is a mode designed to inhibit voice activity through the processing of incompatible language; the Challenging mode introduces dual tasking (as used in eye movement desensitisation and reprocessing) designed to reduce the emotionality and vividness of a voice memory. Two different language games, Lingo Tapper and Word Link, are provided, containing both functions. This study aimed to explore the momentary effects of Temstem on voice-hearing distress, emotionality and vividness in a naturalistic sample of voice-hearing app users. Method: Temstem is freely available in the Netherlands. We collected data through the app from 1048 individual users who had given informed consent for the study. We assessed changes in pre- and post-session scores on distress, emotionality and vividness, and we evaluated differences in outcomes between the games and whether effects remained stable over multiple sessions. Results: Users had been hearing voices for an average of 4.95 years; 79 % had been informed about Temstem by a mental health therapist or coach. After a Silencing session, voice-hearing distress was reduced, t(958) = 27.12, p < .001, d = 0.49; the degree of reduction remained stable after repeated use, F(1, 7905.57) = 1.91, p = .167. After a Challenging session, emotionality, t(651) = 23.16, p < .001, d = 0.74, and the vividness of voice memories were reduced, t(651) = 22.20, p < .001, d = 0.71; both diminished slightly with frequent use, F(1, 2222.86) = 7.21, p < .05; F(1, 2289.92) = 4.25, p < .05. In comparison with Lingo Tapper, larger reductions were seen for a Word Link game: emotionality t(226) = 2.88, p < .005, d = 0.21; vividness t(226) = 2.29, p < .05, d = 0.17. Discussion: In this heterogeneous sample of voice-hearing individuals, Temstem appeared to be a promising coping tool; momentary voice-hearing distress and the emotionality and vividness of voice statements were reduced after a Temstem session. Despite important limitations and the need for more research, naturalistic studies of user app data may yield interesting and generalisable findings.

Differential trajectories of tobacco smoking in people at ultra-high risk for psychosis: Associations with clinical outcomes.

Objective: People at ultra-high risk (UHR) for psychosis have a high prevalence of tobacco smoking, and rates are even higher among the subgroup that later develop a psychotic disorder. However, the longitudinal relationship between the course of tobacco smoking and clinical outcomes in UHR subjects is unknown. Methods: We investigated associations between tobacco smoking and clinical outcomes in a prospective study of UHR individuals (n = 324). Latent class mixed model analyses were used to identify trajectories of smoking severity. Mixed effects models were applied to investigate associations between smoking trajectory class and the course of attenuated psychotic symptoms (APS) and affective symptoms, as assessed using the CAARMS. Results: We identified four different classes of smoking trajectory: (i) Persistently High (n = 110), (ii) Decreasing (n = 29), (iii) Persistently Low (n = 165) and (iv) Increasing (n = 20). At two-year follow-up, there had been a greater increase in APS in the Persistently High class than for both the Persistently Low (ES = 9.77, SE = 4.87, p = 0.046) and Decreasing (ES = 18.18, SE = 7.61, p = 0.018) classes. There were no differences between smoking classes in the incidence of psychosis. There was a greater reduction in the severity of emotional disturbance and general symptoms in the Decreasing class than in the High (ES = -10.40, SE = 3.41, p = 0.003; ES = -22.36, SE = 10.07, p = 0.027), Increasing (ES = -11.35, SE = 4.55, p = 0.014; ES = -25.58, SE = 13.17, p = 0.050) and Low (ES = -11.38, SE = 3.29, p = 0.001; ES = -27.55, SE = 9.78, p = 0.005) classes, respectively. Conclusions: These findings suggests that in UHR subjects persistent tobacco smoking is associated with an unfavorable course of psychotic symptoms, whereas decrease in the number of cigarettes smoked is associated with improvement in affective symptoms. Future research into smoking cessation interventions in the early stages of psychoses is required to shine light on the potential of modifying smoking behavior and its relation to clinical outcomes.