Lisa Charlotte Smith

Background: Childhood traumas increase the risk of psychosis and voice-hearing. While trauma profiles have been identified in voice-hearers, pathways linking these to voice-related distress remain unclear. This study examined between-group differences in mediation by psychological and behavioral variables in profile–distress associations, with potential moderation by gender. Methods: This cross-sectional study derived childhood trauma profiles via latent class analysis of Childhood Trauma Questionnaire (CTQ) scores from 266 voice-hearing Challenge trial participants with schizophrenia-spectrum diagnoses. Mediation analyses (structural equation modeling with bootstrapped 95% confidence intervals for indirect effects) tested between-group differences in indirect effects of negative voice content, persecutory beliefs about voices, voice power, voice relating style, negative self/other beliefs, emotion regulation, depression, and sleep disturbances in the association between childhood trauma profiles (exposure) and voice-related distress (outcome), with gender as a moderator. Hypotheses were preregistered on the Open Science Framework. Reporting followed AGReMA-guidelines. Results: Three childhood trauma profiles were established: (1) ‘variable severity’ ( n = 160), (2) ‘severe neglect and emotional abuse’ ( n = 84), and (3) ‘severe poly-trauma’ ( n = 22). Significant between-group differences in indirect effects were observed for persecutory beliefs about voices (1 < 3), voice power (1 < 3), and sleep disturbances (1 < 2). Age-adjustment revealed a between-group difference in indirect effect of negative self-beliefs (1 < 3). No moderation by gender was found. Conclusions: This is the first investigation of mediators and moderators of childhood trauma profiles and voice-related distress in clinical voice-hearers. Findings suggest that trauma profiles may provide indicators of mediators potentially relevant to inform individualized formulation and therapy planning.

Interventions for eating disorders increasingly aim to target maintaining psychological mechanisms. One hypothesized mechanism is the internal “eating disorder voice.” In this randomized, parallel-group superiority trial, we evaluated a brief virtual reality (VR)-based psychotherapy enabling interaction with a therapist-operated avatar representing this voice, delivered as an adjunct to treatment as usual (TAU), in adults with anorexia nervosa or bulimia nervosa. Ninety-six participants were randomized 1:1, stratified by TAU recruitment site, with concealed block size, to seven sessions of VR-based avatar intervention + TAU (n=48) or TAU (n=48). Outcomes were assessed at baseline, treatment cessation (12 weeks post baseline), and 24 weeks follow-up. The primary outcome was change in eating disorder symptoms, at treatment cessation measured with the Eating Disorder Examination Questionnaire. The primary analysis showed no statistically significant difference in treatment effect at treatment cessation (adjusted mean difference −0.28 points; 95% CI −0.67 to 0.11; Cohen’s d = −0.33; P = 0.15). However, the intervention showed significant improvement on several prespecified secondary outcomes related to the eating disorder voice and motivation for change, as well as exploratory measures of psychological recovery and quality of life. No serious adverse events related to the intervention were observed. In conclusion, virtual reality-based avatar therapy did not reduce overall eating disorder symptom severity beyond treatment as usual but engaged hypothesized psychological mechanisms of change, supporting its potential role as an adjunctive intervention. ClinicalTrials.gov registration: https://clinicaltrials.gov/study/NCT06345040?term=NCT06345040&rank=1, registration date: 14.03.2024. The study protocol was published in PLOS One (Hansen et al., 2025; https://doi.org/10.1371/journal.pone.0319875). The statistical analysis plan was preregistered on the Open Science Framework (https://osf.io/um638/overview). The study was funded by Independent Research Fund Denmark (reference 2096-00078B) and the Research Fund of the Mental Health Services, Capital Region of Denmark.

Background: Auditory verbal hallucinations (voices) are common in schizophrenia spectrum disorders (SSD), and cause significant distress, making them a critical target in psychotherapeutic interventions. AVATAR therapy, conducted on a two-dimensional computer screen and its adaptation virtual reality-assisted therapy (VRT), using three-dimensional virtual reality (VR), have shown promise. Despite the potential of VRT, research exploring how specific VR characteristics can simulate voices experiences and affect therapy outcome remains scarce. Addressing this gap is key to refining VRT for persistent voices. Objective: This qualitative substudy of the CHALLENGE trial explored patient perspectives on modified VRT versions (VRT-Emotions, VRT-Environment, and VRT-Whiteboard) and their therapeutic impact, with the aim to inform intervention refinement and development. Methods: Semistructured interviews were conducted with 15 participants with SSD and persistent voices after undergoing the modified therapies. Data were analyzed within a pragmatist-critical realism orientation, with a hybrid deductive-inductive approach to thematic analysis. Reflexive team dialogues supported analytical rigor. Results: One overarching theme: A challenging yet transformative therapy, and three subthemes, corresponding to the specific modifications, were generated: Emotional connection with voice , Recognizability builds resistance, and The power of the written word. The modifications were generally perceived to enhance therapeutic experience and effectiveness, albeit participants’ perspectives varied and sometimes contrasted. Conclusions: Findings suggest that refining VRT for persistent voices may involve improving avatar's facial expressions, tailoring therapy to voice experiences, and using recognizable VR environments with gradual exposure and selective visual tools. While controlled studies are needed to establish efficacy, these insights offer practical guidance for VRT refinement and development.

Background: Immersive virtual reality–assisted therapy (VRT) is a relational therapy for distressing voices in psychosis. Like AVATAR therapy (AT), VRT centers on therapist-facilitated dialogues with a digital avatar representing a voice. Unlike AT, VRT uses immersive virtual reality (VR). While participant experiences of AT have been explored, therapist perspectives remain unexamined, and for VRT, neither participant nor therapist experiences have been studied. Understanding these perspectives is essential to inform optimization of therapy, future research, and implementation. Objective: The objective of this qualitative study was to explore both trial participants’ and therapists’ experience of VRT in the Challenge trial. Methods: Semistructured interviews were conducted with 10 trial participants and 8 therapists across the 3 Challenge trial sites. Trial participants were purposively sampled to ensure site representation and variation in voice-hearing duration. Individual interviews were conducted with trial participants, while therapists participated in site-based groups with 2‐3 in each. Interviews were audio-recorded, transcribed, and subjected to reflexive thematic analysis from a critical realist position. Coding and theme development were inductive. People with lived experience were invited to an initial focus group for topic guide development and a later theme validation workshop. Reporting followed the Standards of Reporting Qualitative Research (SRQR). Results: A total of five overarching themes were generated: (1) using technology to meet the voice, (2) a different approach to voice-hearing and treatment, (3) on a tight schedule, (4) a toolbox for transformation, and (5) a price to pay. Trial participants and therapists generally found VRT acceptable, appropriate, and feasible. Highlights included the acknowledging approach to the voice(s), facilitation of engagement with the voice(s), and opportunity to share the otherwise private experience of voice-hearing. Externalizing and embodying the voice(s) in VR-supported avatar role-plays was seen as a key affordance. Positive outcomes included increased trial participant empowerment and self-worth, enabling or improving voice dialogue, new understanding of voice intentions, and changes in voice frequency or content. Challenges included instances of participant anxiety, exhaustion, or suboptimal sense of (voice) presence; adverse voice reactions; technological malfunctions and limitations to avatar design; measurement insensitivity; tensions between assertiveness and compassion; difficulties with reproducing negative voice content; and the demanding nature of the therapy and the nontraditional skills required of therapists. Conclusions: The study provided comprehensive insights into trial participants’ and therapists’ experiences of VRT in the Challenge trial. Findings share several similarities with qualitative research on other relational therapies for distressing voices and highlight VRT’s potential for positive change. Key considerations for future research and implementation include monitoring anxiety and voice reactions, ensuring operational reliability of hardware and software, and addressing the additional effort required by therapists, which may be unsustainable in routine practice. As a demanding intervention, the successful implementation of VRT will require adequate training, supervision, and structural support.

Paranoia is a distressing and prevalent symptom in schizophrenia spectrum disorders. Virtual reality-based cognitive behavioral therapy for paranoia (VR-CBTp) has been proposed to augment behavioral interventions by providing controlled and safe virtual environments in which social situations inducing paranoid anxiety can be manipulated, allowing for new therapeutical possibilities such as gradual exposure and repetition. This assessor-masked, randomized parallel group superiority trial investigated the efficacy of VR-CBTp compared to standard CBTp. Participants were randomized to receive ten sessions of VR-CBTp or CBTp, both on top of treatment as usual. Intention-to-treat analyses included 254 participants (VR-CBTp: n = 126, CBTp: n = 128). Outcomes were assessed at baseline, treatment cessation and follow-up (6 months after treatment cessation). The primary outcome was Ideas of Persecution subscale from the Green Paranoid Thoughts Scale, measured at treatment cessation. There was not a statistically significant between-group difference on the primary outcome at endpoint (effect estimate: 2% in favor of VR-CBTp; 95% confidence interval: −11% to +17%; Cohen’s d = 0.04; P = 0.77, based on exponentiated log-transformed data). No deaths or violent incidents involving law enforcement occurred during the study. In conclusion, VR-CBTp was not superior to CBTp in reducing schizophrenia-spectrum-disorders-related paranoia. ClinicalTrials.gov registration: NCT04902066.

Paranoia is a distressing and prevalent symptom in schizophrenia spectrum disorders (SSD). This assessor-masked, randomized parallel group superiority trial investigated the efficacy of virtual reality-based cognitive behavioral therapy (VR-CBT) compared to standard CBT targeting paranoia. A total of 259 participants with SSD and paranoia were randomized to receive 10 sessions of VR-CBT or standard CBT, excluding five who later withdrew informed consent. Intention-to-treat analyses included 254 participants (VR-CBT: n = 126, standard CBT: n = 128). Outcomes were assessed at baseline, treatment cessation (3 months) and follow-up (9 months). The primary outcome was the Green Paranoid Thought Scale (GPTS) subscale Ideas of Persecution, measured at treatment cessation. Linear mixed-model analyses revealed no statistically significant difference between the groups at endpoint (adjusted mean difference 1.12, 95% CI: -1.75 to 3.99 Cohen’s d=0.10; p=0.44). Both groups demonstrated large with-in group improvements on the primary outcome (VR-CBT: Cohen’s d=0.88; standard CBT: Cohen’s d=0.87). No deaths or violent incidents involving law enforcement occurred during the study. These findings do not support the superiority of VR-CBT over standard CBT; rather, both interventions significantly reduced paranoia and represent promising treatment options for SSD-related paranoia. ClinicalTrials.gov identifier NCT04902066.

Auditory verbal hallucinations (AVH) are frequent and debilitating symptoms of schizophrenia spectrum disorders (SSD). In the current randomized, assessor-blinded, parallel-group superiority clinical trial, a total of 270 participants, diagnosed with SSD suffering from treatment-resistant AVH, were randomly assigned to seven sessions of either a virtual reality-assisted therapy (Challenge-VRT) or supportive counselling. Assessment of outcome was conducted at baseline, and at 12 and 24 weeks post baseline. Linear mixed model analyses demonstrated that Challenge-VRT significantly reduced the symptom load of AVH on the primary outcome measured with the Psychotic Symptoms Rating Scales (PSYRATS-AH total, adjusted mean difference: -2.26, 95% Cl: -4.26 to -0.25, p = 0.03) and the secondary outcome measure on frequency of AVH (PSYRATS-Frequency, adjusted mean difference: -0.84, 95% Cl: -1.53 to -0.14, p = 0.02) at treatment cessation 12 weeks post baseline. We conclude that the brief Challenge-VRT is a viable new treatment method for reducing the severity of AVH. ClinicalTrials.gov identifier NCT04661163

Background: Many patients suffering from schizophrenia spectrum disorders continue having distressing auditory hallucinations in spite of treatment with antipsychotic medication. The aim of this trial is to examine the effect of a targeted virtual reality therapy for persistent auditory hallucinations in individuals with psychosis. The trial explores whether this type of therapy can decrease the severity, frequency and distress of auditory hallucinations and, additionally, whether it can reduce clinical symptoms and enhance daily functioning in individuals with psychosis. Methods: The study is a randomised, assessor-blinded parallel-group superiority clinical trial, allocating a total of 266 patients to either the experimental intervention or supportive counselling. The participants will be randomised to either (1) seven sessions of virtual reality therapy or (2) seven sessions of supportive counselling to be delivered within the first 12 weeks after inclusion in the study. All participants will be assessed at baseline and 12 and 24 weeks post-baseline. Independent assessors blinded to the treatment allocation will evaluate the outcome. The primary outcome is the level of auditory hallucinations measured with the Psychotic Symptoms Rating Scales (PSYRATS-AH) total score at the cessation of treatment at 12 weeks. Secondary outcomes are frequency of auditory hallucinations, the distress caused by auditory hallucinations, perceived voice power, patient acceptance of voices, patients’ ability to respond to voices in an assertive way and social and daily function. Discussion: Promising evidence of the efficacy of this immersive virtual reality-based therapy for auditory hallucinations exist, but evidence needs to be established in a large, methodological rigorous trial. If the therapy proves to be beneficial in reducing the severity of refractory auditory hallucinations, a large group of patients with schizophrenia and related disorders could be the target group of this short-term psychotherapeutic intervention.

Background: Many patients suffering from schizophrenia spectrum disorders continue having distressing auditory hallucinations in spite of treatment with antipsychotic medication. The aim of this trial is to examine the effect of a targeted virtual reality therapy for persistent auditory hallucinations in individuals with psychosis. The trial explores whether this type of therapy can decrease the severity, frequency, and distress of auditory hallucinations and additionally, whether it can reduce clinical symptoms and enhance daily functioning in individuals with psychosis. Methods: The study is a randomised, assessor-blinded parallel-groups superiority clinical trial, allocating a total of 266 patients to either the experimental intervention or supportive counselling. The participants will be randomised to either 1) seven sessions of virtual reality therapy or 2) seven sessions of supportive counselling to be delivered within the first 12 weeks after inclusion in the study. All participants will be assessed at baseline and 12- and 24 weeks post baseline. Independent assessors blinded to treatment allocation will evaluate outcome. The primary outcome is the level of auditory hallucinations measured with The Psychotic Symptoms Rating Scales (PSYRATS-AH) total score at cessation of treatment at 12-weeks. Secondary outcomes are frequency of auditory hallucinations, the distress caused by auditory hallucinations, perceived voice power, patient acceptance of voices, patients’ ability to respond to voices in an assertive way and social and daily function. Discussion: Promising evidence exist of the efficacy of this immersive virtual reality-based therapy for auditory hallucinations, but evidence needs to be established in a large, methodological rigorous trial. If the therapy proves to be beneficial in reducing the severity of refractory auditory hallucinations, a large group of patients with schizophrenia and related disorders could be the target group of this short-term psychotherapeutic intervention.