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Immersive virtual reality (VR) has been identified as a potentially revolutionary tool for psychological interventions. This study reviews current advances in immersive VR-based therapies for mental disorders. VR has the potential to make psychiatric treatments better and more cost-effective and to make them available to a larger group of patients. However, this may require a new generation of VR therapeutic techniques that use the full potential of VR, such as embodiment, and self-led interventions. VR-based interventions are promising, but further well-designed studies are needed that use novel techniques and investigate efficacy, efficiency, and cost-effectiveness of VR interventions compared with current treatments. This will be crucial for implementation and dissemination of VR in regular clinical practice.

Background Seventy per cent of patients with psychotic disorders has paranoid delusions. Paranoid delusions are associated with significant distress, hospital admission and social isolation. Cognitive-behavioural therapy for psychosis (CBTp) is the primary psychological treatment, but the median effect size is only small to medium. Virtual reality (VR) has a great potential to improve the effectiveness of CBTp. In a previous study, we found that VR based CBT (VRcbt) for paranoid delusions is superior to waiting list. As a next step, a direct comparison with CBTp is needed. The present study aims to investigate whether VRcbt is more effective and cost-effective than regular CBTp in treating paranoid delusions and improving daily life social functioning of patients with psychotic disorders. Methods A total of 106 patients with DSM-5 diagnosis of psychotic disorder and at least moderate level of paranoid ideations will be recruited for this multicentre randomized controlled trial (RCT). Patients will be randomized to either VRcbt or standard CBTp for paranoid delusions. VRcbt consists of maximum 16 sessions in virtual social situations that trigger paranoid ideations and distress, delivered in an 8–12 week time frame. Standard CBTp also consists of maximum 16 sessions including exposure and behavioural experiments, delivered in an 8–12 week time frame. The two groups will be compared at baseline, post-treatment and six months follow-up. Primary outcome is the level of paranoid ideations in daily life social situations, measured with ecological momentary assessments (EMA) at semi-random moments ten times a day during seven days, before and after treatment. Every session, participants and therapists will rate the level of paranoid ideation and global clinical impression. Discussion Comparison of VRcbt and CBTp will provide information about the relative (cost-) effectiveness of VRcbt for this population. VRcbt may become a preferred psychological treatment for paranoid delusions and social anxiety in patients with psychotic disorder. Trial registration Netherlands Trial Register, NL7758. Registered on 23 May 2019.

Background: Higher liability to psychosis is associated with low self-esteem and increased sensitivity to social stress. Recently, we reported a positive relation between liability to psychosis and affective and psychotic responses to social stress. This study investigated how self-esteem moderates paranoia, peak subjective distress and stress reactivity of people with different psychosis liability in response to social stressors in virtual reality.Methods: Ninety-four individuals with lower (41 siblings and 53 controls) and 75 persons with higher psychosis liability (55 with recent onset psychotic disorder and 20 at ultra-high risk for psychosis) explored five times a virtual cafe with various social stressors (crowdedness, ethnic minority status, and hostility). They rated momentary paranoia (State Social Paranoia Scale) after each experiment and subjective distress on a visual analogue scale before and after the experiments. Positive and negative self-esteem were assessed with the Self-Esteem Rating Scale.Results: Momentary paranoia, peak subjective distress, and reactivity to social stressors were associated with negative self-esteem, but not positive self-esteem. Effects of both positive and negative self-esteem on psychotic and affective stress responses, but not stress reactivity, became significantly stronger when individuals were exposed to more stressful environments. Effects of self-esteem on momentary paranoia and peak subjective distress did not differ between the high liability and low liability group. Persons with lower psychosis liability had a stronger effect of negative self-esteem on stress reactivity than persons with higher liability.Conclusions: Positive and negative self-esteem may play an important role in affective and psychotic responses to social stress. (C) 2018 Elsevier B.V. All rights reserved.

Background: Negative affective processes may contribute to maintenance of paranoia in patients with psychosis, and vice versa. Successful treatment may break these pathological symptom networks. This study examined whether treatment with virtual reality based cognitive behavioral therapy (VR-CBT) for paranoia influences momentary affective states, and whether VR-CBT changes the adverse interplay between affective states and paranoia.Methods: Patients with a psychotic disorder (n = 91) were randomized to 16-session VR-CBT or treatment as usual (TAU). With the experience sampling method (structured diary technique) mental states were assessed for 6-10 days at baseline, post treatment and 6-month follow-up. Multilevel analysis were performed to establish treatment effects and time-lagged associations between mental states, that were visualized with networks of mental states.Results: Average levels of paranoia (feeling suspicious [b = -032., p = .04], disliked [b = -49., p < .01] and hurt [b = -0.52, p < .01]) and negative affect (anxious [b = -0.37, p = .01], down [b = -0.33, p = .04] and insecure [b = -0.17, p = .03) improved more after VR-CBT than TAU, but positive affect did not. Baseline mental state networks had few significant connections, with most stable connections being autocorrelations of mental states. The interplay between affective states and paranoia did not change in response to treatment. A trend reduction in average intranode connections (autocorrelations) was found after VR-CBT (b = -0.07, p = .08), indicating that mental states reinforce themselves less after treatment.Conclusions: VR-CBT reduced paranoid symptoms and lowered levels of negative affect in daily life, but did not affect the extent to which mental states influenced each other. Findings do suggest that as a result of treatment mental states regain flexibility. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background Evidence was found for the effectiveness of virtual reality-based cognitive behavioral therapy (VR-CBT) for treating paranoia in psychosis, but health-economic evaluations are lacking. Objective This study aimed to determine the short-term cost-effectiveness of VR-CBT. Methods The health-economic evaluation was embedded in a randomized controlled trial evaluating VR-CBT in 116 patients with a psychotic disorder suffering from paranoid ideation. The control group (n=58) received treatment as usual (TAU) for psychotic disorders in accordance with the clinical guidelines. The experimental group (n=58) received TAU complemented with add-on VR-CBT to reduce paranoid ideation and social avoidance. Data were collected at baseline and at 3 and 6 months postbaseline. Treatment response was defined as a pre-post improvement of symptoms of at least 20% in social participation measures. Change in quality-adjusted life years (QALYs) was estimated by using Sanderson et al’s conversion factor to map a change in the standardized mean difference of Green’s Paranoid Thoughts Scale score on a corresponding change in utility. The incremental cost-effectiveness ratios were calculated using 5000 bootstraps of seemingly unrelated regression equations of costs and effects. The cost-effectiveness acceptability curves were graphed for the costs per treatment responder gained and per QALY gained. Results The average mean incremental costs for a treatment responder on social participation ranged between €8079 and €19,525, with 90.74%-99.74% showing improvement. The average incremental cost per QALY was €48,868 over the 6 months of follow-up, with 99.98% showing improved QALYs. Sensitivity analyses show costs to be lower when relevant baseline differences were included in the analysis. Average costs per treatment responder now ranged between €6800 and €16,597, while the average cost per QALY gained was €42,030. Conclusions This study demonstrates that offering VR-CBT to patients with paranoid delusions is an economically viable approach toward improving patients’ health in a cost-effective manner. Long-term effects need further research. Trial Registration International Standard Randomised Controlled Trial Number (ISRCTN) 12929657; http://www.isrctn.com/ISRCTN12929657

Introduction: Cognitive biases are associated with psychosis liability and paranoid ideation. This study investigated the moderating relationship between pre-existing self-reported cognitive biases and the occurrence of paranoid ideation in response to different levels of social stress in a virtual reality environment.Methods: This study included 170 participants with different levels of psychosis liability (55 recent onset psychosis, 20 ultrahigh risk for psychosis, 42 siblings of psychotic patients, and 53 controls). All participants were exposed to virtual environments with different levels of social stress. The level of experienced paranoia in the virtual environments was measured with the State Social Paranoia Scale. Cognitive biases were assessed with a self-report continuous measure. Also, cumulative number of cognitive biases was calculated using dichotomous measures of the separate biases, based on general population norm scores.Results: Higher belief inflexibility bias (Z = 2.83, P < .001), attention to threat bias (Z = 3.40, P < .001), external attribution bias (Z = 2.60, P < .001), and data-gathering bias (Z = 2.07, P < .05) were all positively associated with reported paranoid ideation in the social virtual environments. Level of paranoid response increased with number of cognitive biases present (B = 1.73, P < .001). The effect of environmental stressors on paranoid ideation was moderated by attention to threat bias (Z = 2.78, P < .01) and external attribution bias (Z = 2.75, P < .01), whereas data-gathering bias and belief inflexibility did not moderate the relationship.Conclusion: There is an additive effect of separate cognitive biases on paranoid response to social stress. The effect of social environmental stressors on paranoid ideation is further enhanced by attention to threat bias and external attribution bias.

The use of virtual reality (VR) in psychological treatment is expected to increase. Cybersickness (CS) is a negative side effect of VR exposure and is associated with treatment dropout. This study aimed to investigate the following: (a) if gender differences in CS can be replicated, (b) if differences in anxiety and CS symptoms between patients and controls can be replicated, and (c) whether the relationship between exposure to VR and CS symptoms is mediated by anxiety. A sample (N = 170) of participants with different levels of psychosis liability was exposed to VR environments. CS and anxiety were assessed with self-report measures before and after the VR experiment. This study replicated gender differences in CS symptoms, most of which were present before exposure to VR. It also replicated findings that a significant correlation between anxiety and CS can be found in healthy individuals, but not in patients. In a VR environment, anxiety partially mediated CS symptoms, specifically nausea and disorientation. A partial explanation for the differences found between patients and controls may lie in a ceiling effect for the symptoms of CS. A second explanation may be the partial overlap between CS symptoms and physiological anxiety responses. CS symptoms reported at baseline cannot be explained by exposure to VR, but are related to anxiety. Caution is required when interpreting studies on both CS and anxiety, until the specificity in measurements has been improved. Since anxiety mediated the CS symptoms, CS is expected to decline during treatment together with the reduction of anxiety.

BACKGROUND Evidence was found for the effectiveness of virtual reality-based cognitive behavioral therapy (VR-CBT) for treating paranoia in psychosis, but health-economic evaluations are lacking. OBJECTIVE This study aimed to determine the short-term cost-effectiveness of VR-CBT. METHODS The health-economic evaluation was embedded in a randomized controlled trial evaluating VR-CBT in 116 patients with a psychotic disorder suffering from paranoid ideation. The control group (n=58) received treatment as usual (TAU) for psychotic disorders in accordance with the clinical guidelines. The experimental group (n=58) received TAU complemented with add-on VR-CBT to reduce paranoid ideation and social avoidance. Data were collected at baseline and at 3 and 6 months postbaseline. Treatment response was defined as a pre-post improvement of symptoms of at least 20% in social participation measures. Change in quality-adjusted life years (QALYs) was estimated by using Sanderson et al’s conversion factor to map a change in the standardized mean difference of Green’s Paranoid Thoughts Scale score on a corresponding change in utility. The incremental cost-effectiveness ratios were calculated using 5000 bootstraps of seemingly unrelated regression equations of costs and effects. The cost-effectiveness acceptability curves were graphed for the costs per treatment responder gained and per QALY gained. RESULTS The average mean incremental costs for a treatment responder on social participation ranged between €8079 and €19,525, with 90.74%-99.74% showing improvement. The average incremental cost per QALY was €48,868 over the 6 months of follow-up, with 99.98% showing improved QALYs. Sensitivity analyses show costs to be lower when relevant baseline differences were included in the analysis. Average costs per treatment responder now ranged between €6800 and €16,597, while the average cost per QALY gained was €42,030. CONCLUSIONS This study demonstrates that offering VR-CBT to patients with paranoid delusions is an economically viable approach toward improving patients’ health in a cost-effective manner. Long-term effects need further research. CLINICALTRIAL International Standard Randomised Controlled Trial Number (ISRCTN) 12929657; http://www.isrctn.com/ISRCTN12929657

Psychosis is a multifactorial condition arising from an interaction between genetic liability and exposure to environmental risk factors, in particular childhood trauma. Furthermore, accumulating evidence supports a role for the immune system in the aetiology of psychosis. Increased peripheral levels of pro-inflammatory cytokines and reduced neurotrophic factors are found in patients with psychosis. Childhood trauma is highly prevalent in psychosis patients and is also associated with increased pro-inflammatory cytokines and reduced neurotrophic factors. Recent studies suggest the increase in pro-inflammatory cytokines and decrease in neurotrophic factors seen in psychosis may be attributable to the effects of child maltreatment. The aim of this study was to improve understanding of the relation between childhood trauma, inflammation and psychosis. We examined separate and interaction effects of psychosis liability and childhood trauma on serum levels of BDNF, CCL-2, CRP, IFN-gamma, IGFBP2, IL-6, PDGF, SCF and TNF-alpha in 40 patients with recent onset psychosis, 13 patients at Ultra-High Risk (UHR) for psychosis, 31 unaffected siblings of psychosis patients and 41 healthy controls. Childhood trauma was assessed retrospectively with the Childhood Trauma Questionnaire (CTQ). No statistically significant effects of psychosis liability or childhood trauma on concentrations of cytokines or growth factors in peripheral blood were found, nor were there any statistically significant interaction effects of psychosis liability with childhood trauma on serum levels of cytokines and growth factors.

BackgroundChildhood trauma is associated with higher risk for mental disorders, including psychosis. Heightened sensitivity to social stress may be a mechanism. This virtual reality study tested the effect of childhood trauma on level of paranoid ideations and distress in response to social stress, in interaction with psychosis liability and level of social stress exposure.MethodSeventy-five individuals with higher psychosis liability (55 with recent onset psychotic disorder and 20 at ultra-high risk for psychosis) and 95 individuals with lower psychosis liability (42 siblings and 53 controls) were exposed to a virtual café in five experiments with 0–3 social stressors (crowded, other ethnicity and hostility). Paranoid ideation was measured after each experiment. Subjective distress was self-rated before and after experiments. Multilevel random regression analyses were used to test main effects of childhood trauma and interaction effects.ResultsChildhood trauma was more prevalent in individuals with higher psychosis liability, and was associated with higher level of (subclinical) psychotic and affective symptoms. Individuals with a history of childhood trauma responded with more subjective distress to virtual social stress exposures. The effects of childhood trauma on paranoia and subjective distress were significantly stronger when the number of virtual environmental stressors increased. Higher psychosis liability increased the effect of childhood trauma on peak subjective distress and stress reactivity during experiments.ConclusionsChildhood trauma is associated with heightened social stress sensitivity and may contribute to psychotic and affective dysregulation later in life, through a sensitized paranoid and stress response to social stressors.

Background Recently, the efficacy of a novel virtual reality based cognitive behavior therapy (VR-CBT) for paranoia was demonstrated. Evidence is growing that the maintenance of psychosis may be influenced by affective processes. This study examined how treatment with VR-CBT influenced positive and negative affect states, and whether the interplay between mental states was affected. Methods The sample consisted of 91 patients with a psychotic disorder randomized either to 16-session individual VR-CBT or treatment as usual. The experience sampling method (ESM; a structured diary technique) was used to assess mental states at baseline, post-intervention and 6-month follow-up. Mixed model analyses were conducted to study treatment effects. Lagged associations between mental states were estimated at baseline and post-intervention, and were visualized with networks. Results VR-CBT, but not treatment as usual, resulted in reduced levels of paranoia and negative affect. At pre-intervention networks depicting the dynamic interplay between mental states over time had limited significant connections, with most stable connections being auto-relations. I.e., paranoia was best predicted by paranoia at the previous moment. The dynamic interplay between affective states did not change over time after VR-CBT. Discussion We found that VR-CBT specifically targets paranoia and there are indications that VR-CBT had an enduring effect on negative emotions. These beneficial treatment effects do not seem to transfer to positive affective states. Unexpectedly, we did not find evidence that negative mental states such as feeling down or lonely triggered paranoia in the next moment even at pre-intervention, and these temporal relations between mental states did not change over time in response to treatment.

BACKGROUND: Psychotic disorders are characterized by a deranged immune system, including altered number and function of Natural Killer (NK) and T cells. Psychotic disorders arise from an interaction between genetic vulnerability and exposure to environmental risk factors. Exposure to social adversity during early life is particularly relevant to psychosis risk and is thought to increase reactivity to subsequent minor daily social stressors. Virtual reality allows controlled experimental exposure to virtual social stressors.AIM: To investigate the interplay between social adversity during early life, cell numbers of NK cells and T helper subsets and social stress reactivity in relation to psychosis liability.METHODS: Circulating numbers of Th1, Th2, Th17, T regulator and NK cells were determined using flow cytometry in 80 participants with low psychosis liability (46 healthy controls and 34 siblings) and 53 participants with high psychosis liability (14 ultra-high risk (UHR) patients and 39 recent-onset psychosis patients), with and without the experience of childhood trauma. We examined if cell numbers predicted subjective stress when participants were exposed to social stressors (crowdedness, hostility and being part of an ethnic minority) in a virtual reality environment.RESULTS: There were no significant group differences in Th1, Th2, Th17, T regulator and NK cell numbers between groups with a high or low liability for psychosis. However, in the high psychosis liability group, childhood trauma was associated with increased Th17 cell numbers (p = 0.028). Moreover, in the high psychosis liability group increased T regulator and decreased NK cell numbers predicted stress experience during exposure to virtual social stressors (p = 0.015 and p = 0.009 for T regulator and NK cells, respectively).CONCLUSION: A deranged Th17/T regulator balance and a reduced NK cell number are associated intermediate biological factors in the relation childhood trauma, psychosis liability and social stress reactivity.

BACKGROUND: Many patients with psychotic disorders have persistent paranoid ideation and avoid social situations because of suspiciousness and anxiety. We investigated the effects of virtual-reality-based cognitive behavioural therapy (VR-CBT) on paranoid thoughts and social participation.METHODS: In this randomised controlled trial at seven Dutch mental health centres, outpatients aged 18-65 years with a DSM-IV-diagnosed psychotic disorder and paranoid ideation in the past month were randomly assigned (1:1) via block randomisation to VR-CBT (in addition to treatment as usual) or the waiting list control group (treatment as usual). VR-CBT consisted of 16 individual therapy sessions (each 1 h long). Assessments were done at baseline, after treatment (ie, 3 months from baseline), and at a 6 month follow-up visit. The primary outcome was social participation, which we operationalised as the amount of time spent with other people, momentary paranoia, perceived social threat, and momentary anxiety. Analysis was by intention to treat. This trial was retrospectively registered with ISRCTN, number 12929657.FINDINGS: Between April 1, 2014, and Dec 31, 2015, 116 patients with a psychotic disorder were randomly assigned, 58 to the VR-CBT group and 58 to the waiting list control group. Compared with the control, VR-CBT did not significantly increase the amount of time spent with other people at the post-treatment assessment. Momentary paranoid ideation (b=-0·331 [95% CI -0·432 to -0·230], pINTERPRETATION: Our results suggest that the addition of VR-CBT to standard treatment can reduce paranoid ideation and momentary anxiety in patients with a psychotic disorder.FUNDING: Fonds NutsOhra, Stichting tot Steun VCVGZ.

The impact of social environments on mental states is difficult to assess, limiting the understanding of which aspects of the social environment contribute to the onset of psychotic symptoms and how individual characteristics moderate this outcome. This study aimed to test sensitivity to environmental social stress as a mechanism of psychosis using Virtual Reality (VR) experiments. Fifty-five patients with recent onset psychotic disorder, 20 patients at ultra high risk for psychosis, 42 siblings of patients with psychosis, and 53 controls walked 5 times in a virtual bar with different levels of environmental social stress. Virtual social stressors were population density, ethnic density and hostility. Paranoia about virtual humans and subjective distress in response to virtual social stress exposures were measured with State Social Paranoia Scale (SSPS) and self-rated momentary subjective distress (SUD), respectively. Pre-existing (subclinical) symptoms were assessed with the Community Assessment of Psychic Experiences (CAPE), Green Paranoid Thoughts Scale (GPTS) and the Social Interaction Anxiety Scale (SIAS). Paranoia and subjective distress increased with degree of social stress in the environment. Psychosis liability and pre-existing symptoms, in particular negative affect, positively impacted the level of paranoia and distress in response to social stress. These results provide experimental evidence that heightened sensitivity to environmental social stress may play an important role in the onset and course of psychosis.

Background: Social stressors are associated with an increased risk of psychosis. Stress sensitisation is thought to be an underlying mechanismand may be reflected in an altered autonomic stress response. Using an experimental Virtual Reality design, the autonomic stress response to social stressorswas examined in participantswith different liability to psychosis.Method: Fifty-five patients with recent onset psychotic disorder, 20 patients at ultra-high risk for psychosis, 42 siblings of patientswith psychosis and 53 controls were exposed to social stressors (crowdedness, ethnicminority status and hostility) in a Virtual Reality environment. Heart rate variability parameters and skin conductance levels were measured at baseline and during Virtual Reality experiments.Results: High psychosis liability groups had significantly increased heart rate and decreased heart rate variability compared to low liability groups both at baseline and during Virtual Reality experiments. Both low frequency (LF) and high frequency (HF) power were reduced, while the LF/HF ratiowas similar between groups. The number of virtual social stressors significantly affected heart rate, HF, LF/HF and skin conductance level. There was no interaction between psychosis liability and amount of virtual social stress.Conclusion: High liability to psychosis is associated with decreased parasympathetic activity in virtual social environments, which reflects generally high levels of arousal, rather than increased autonomic reactivity to social stressors. (C) 2016 Elsevier B.V. All rights reserved.

A large number of patients with a psychotic disorder live a life of limited participation in society, even if their psychotic symptoms have been treated successfully. An important factor in sustaining social isolation is that when social anxiety and distrust increase, the patient has learned to flee the situation and as a consequence experiences a reduction in anxiety. In this study we study the use of Virtual Reality Exposure Therapy (VRET) to enhance social participation and wellbeing for patients suffering from a psychotic disorder and social withdrawal. The study design is a single blind RCT with three-month follow-up. The VRET.P treatment consists of sixteen treatment sessions of sixty minutes each, within an eight-week timeframe. Social participation was measured by the PsyMate Experience Sampling Method before and at end of treatment, and at three-month follow-up. One hundred and sixteen participants were included in the study. Fifty-eight participants received the VRET.P treatment right away. The other fiftyeight participants received treatment as usual during the study, and were offered the VRET.P treatment after the follow-up measurement. We have finished data collection for the study; the last follow-up measurements have taken place in December 2015. We will be able to present the results of the study in June 2016 on the conference. Clinical implications and limitations of the results and the study will be discussed.

Many patients with a psychotic disorder participate poorly in society. When psychotic disorders are in partial remission, feelings of paranoia, delusions of reference, social anxiety and self-stigmatization often remain at diminished severity and may lead to avoidance of places and people. Virtual reality exposure therapy (VRET) is an evidence-based treatment for several anxiety disorders. For patients with a psychotic disorder, the VRETp was developed to help them experience exposure to feared social situations. The present study aims to investigate the effects of VRETp on social participation in real life among patients with a psychotic disorder. The study is a single-blind randomized controlled trial with two conditions: the active condition, in which participants receive the virtual reality treatment together with treatment as usual (TAU), and the waiting list condition, in which participants receive TAU only. The two groups are compared at baseline, at 3 months posttreatment and at 6 months follow-up. All participants on the waiting list are also offered the virtual reality treatment after the follow-up measurements are completed. The primary outcome is social participation. Secondary outcomes are quality of life, interaction anxiety, depression and social functioning in general. Moderator and mediator analyses are conducted with stigma, cognitive schemata, cognitive biases, medication adherence, simulator sickness and presence in virtual reality. If effective, a cost-effectiveness analysis will be conducted. Results from the posttreatment measurement can be considered strong empirical indicators of the effectiveness of VRETp. The 6-month follow-up data may provide reliable documentation of the long-term effects of the treatment on the outcome variables. Data from pre-treatment and mid-treatment can be used to reveal possible pathways of change. Current Controlled Trials: ISRCTN12929657 . Date of registration: 8 September 2015

Background Recently, the efficacy of a novel virtual reality based cognitive behavior therapy (VR-CBT) for paranoia was demonstrated. Cognitive biases, cognitive limitations, negative schematic beliefs and safety behavior have been associated with paranoid ideations and delusions. It is unknown whether VR-CBT affects these associated factors, and how changes in these factors relate to changes in paranoid ideation. Methods In this multi-center randomized controlled trial patients with a psychotic disorder and paranoia were randomized to VR-CBT (n = 58) or treatment as usual (TAU; n = 58). VR-CBT consisted of maximally sixteen 60-minute individual therapy sessions. Paranoia, safety behavior, schematic beliefs, cognitive biases and limitations were assessed at baseline, post-treatment (at three months) and follow-up (at six months). Mixed model analyses were conducted to study treatment effects. Mediation analyses were performed to explore putative working mechanisms by which VR-CBT reduced paranoia. Results VR-CBT, but not TAU, led to reductions in jumping to conclusions, attention for threat bias and social cognition problems. Schematic beliefs remained unaffected. The effect of VR-CBT on paranoia was mediated by reductions in safety behavior and social cognition problems. Discussion VR-CBT affects multiple mechanisms that are associated with paranoid ideation. Although maintaining factors of paranoia are likely to influence each other, targeting safety behavior and social cognitive problems seems effective in breaking the vicious circle of paranoia.

Background: Psychotic syndromes can be understood as disorders of adaptation to social context. It is not clear, however, how symptoms of psychosis develop in the daily social environment, in interaction with individual liability. Virtual Reality (VR) technology may help to investigate relationships between environment and psychosis, as it allows controlled exposure to various social risk environments. Methods: Four groups (total N=54) with different liability to psychosis (patients with first episode psychosis (FEP), siblings, ultra high risk individuals (UHR) and healthy controls) were exposed to virtual social environments. Psychological and physiological responses were measured repeatedly. The virtual environment was varied with regard to social stressors (population density, ethnic density and hostility of avatars). Results: Paranoid thoughts and social anxiety in real life correlated significantly with paranoid thoughts about avatars and subjective distress in virtual social stress environments (Spearman's correlation coefficients 0.4 0.5, p