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.

Virtual reality-assisted assessment of paranoid ideation in forensic psychiatric inpatients: A mixed-methods pilot study.

Background: Reliable and valid assessment of paranoia is important in forensic psychiatry for providing adequate care. VR technology may add to current assessment procedures, as it enables observation within realistic (social) situations resembling the complexity of everyday life. VR constitutes a promising tool within forensics, due to the restricted nature of forensic psychiatric hospitals and ethical challenges arising from observing potentially dangerous behaviors in real life. Objective: To investigate the feasibility of VR assessment for paranoid ideation in forensic psychiatric inpatients qualitatively by assessing the experiences of patients and a clinician, and to explore how the VR measures relate to established clinical measures. Methods: One clinician (experienced psychiatrist) and 10 forensic psychiatric inpatients with a history or suspicion of paranoid ideation were included. Patients participated in two immersive VR scenarios (bus and supermarket) during which paranoia was assessed by the clinician. Qualitative interviews were performed with patients and the clinician performing the assessment to investigate experiences and feasibility. Further, measures of paranoia, social anxiety, and positive symptoms were obtained. Results: Nine out of 10 participants with varying levels of paranoid ideation completed the assessment. Manifest inductive content analyses of the interviews revealed general experiences, advantages such as enabling observing participants from a different perspective, and challenges of the VR assessment, such as a lack of objectivity and the laboriousness of the assessment for the clinician. Although more paranoia was experienced during the supermarket scenario, correlates with classical measures were only significant for the bus scenario. Discussion: The VR assessment was appreciated by most patients and the clinician. Based on our results short, standardized VR assessment scenarios are feasible, however, they do not appear reliable or objective for assessing paranoia. The clinical usefulness is most likely as a collaborative tool and add-on measure to existing methods.

Virtual reality aggression prevention treatment in a Dutch prison-based population: a pilot study.

Background: Treating violent behavior in prisons comes with challenges, such as the inability to practice safely with triggering situations and motivational issues. A solution may be the use of Virtual Reality (VR). With VR, specific conditions or needs can be tailored for individual practice, it can enhance motivation and VR has proven to be a safe and effective tool in mental health treatment. Objective: A pilot study was conducted to test the acceptability, feasibility, and preliminary effects of VR Aggression Prevention Treatment (VRAPT) in a prison-based population. Methods: In total 17 detainees with aggressive behavior were included in this single-group pilot study. Acceptability and feasibility were assessed using qualitative measures for participants and therapists. Preliminary treatment effects were measured with self-report and observational measures on aggression, anger, emotion regulation, and impulsiveness. Results: Participants and therapists were predominantly positive about VRAPT. Participants rated the sessions with an average satisfaction score of 9.2 out of 10 (SD = 0.3). Qualitative data showed that participants reported having learned to respond more adequately to aggressive behavior and gained insights into their own and others' triggers and tension. The combination of VR and theory was experienced as a strength of the treatment, as well as the ability to trigger aggression in VR which provided insights into aggression. However, the theoretical framework was found to be too complex, and more aggressive and personal scenarios should be incorporated into the sessions. Self-reported aggression, anger, provocation, emotion regulation, and observed verbal aggression decreased and seemed to stabilize after the treatment ended, with small to medium effect sizes. Conclusion: VRAPT proved feasible and acceptable for most participants and therapists. An adapted treatment protocol called Virtual Reality Treatment for Aggression Control (VR-TrAC), will be used in a future RCT to investigate the effects of the treatment in a prison-based population.

Longitudinal clinical and functional outcome in distinct cognitive subgroups of first-episode psychosis: a cluster analysis.

BACKGROUND: Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes. METHODS: 204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up. RESULTS: Three distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present. CONCLUSIONS: Current results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.

Use of Virtual Reality in Psychiatric Diagnostic Assessments: A Systematic Review.

Background: Technological developments such as Virtual reality (VR) provide new opportunities to extend and innovate mental healthcare. VR as a tool for clinical assessment has been described as promising, as it can enable real-time assessment within real-like environments or contexts as opposed to self-report and behavioral tasks in laboratory settings. Objective: With this systematic review we aimed to provide an overview of recent studies using VR in the assessment of psychiatric disorders. Methods: A systematic search was performed using Pubmed, Embase, PsycInfo, and Web of Science between 2016 and 2020. Studies were included if they used immersive VR, concerned assessment of psychiatric symptoms/disorders, and included adult patients with psychiatric disorders. Results: The search resulted in 3,163 potentially eligible articles, from which a total of 27 studies fulfilled inclusion criteria. Most studies considered anxiety (n = 7), addictive, (n = 7), or psychotic disorders (n = 5). Regarding ADHD (n = 3), PTSD (n = 3), and pedophilic disorder (n = 1), a few studies had been performed since 2016. The majority of the included studies compared patient groups to healthy control groups. Discussion: Recent studies on VR-assisted psychiatric assessments have been conducted to validate VR environments, to assess symptoms for diagnostics or therapy goals, search for biomarkers, and to gain knowledge on psychiatric disorders. VR tasks were able to detect some difference between patient and healthy control groups, mainly with regard to self-report measures. Despite previous, promising prospects, the use of VR as a tool in clinical assessments must still be considered as a field in need of continued developments and evaluations. Systematic Review Registration: www.crd.york.ac.uk/prospero, identifier: CRD42021233772.

Cognitive behavioral group treatment for low self-esteem in psychosis: a proof of concept study.

BACKGROUND: Patients with a psychotic disorder often suffer from low self-esteem, which has been related to higher suicidal risk, poor quality of life and, the maintenance of psychotic and depression symptoms. However, intervention studies are scarce and reported interventions concern individual therapies provided by highly educated psychologists. Both the individual setting and the required qualifications of the therapist may contribute to a low level of availability of an intervention. Therefore we aimed to investigate the efficacy of an easily accessible psychological group treatment targeting self-esteem in patients with a psychotic disorder. METHODS: Thirty patients with a psychotic disorder were included in this pilot study. All participants received nine weekly group sessions of 90 min. The therapy was offered in groups of six to eight patients and was provided by a psychiatry nurse and a graduate psychologist. To assess self-esteem the Rosenberg Self-esteem Scale and the Self-Esteem Rating Scale were used, to measure depression symptoms the Beck Depression Inventory-II was administered. Questionnaires were completed at baseline and post-treatment. RESULTS: Twenty-seven patients (90%) completed treatment. At post-treatment, self-esteem was significantly increased and depression symptoms were significantly decreased compared to baseline. DISCUSSION: This pilot study demonstrates the feasibility and treatment potential of a self-esteem group treatment provided by a psychiatry nurse and graduate psychologist in a patient population that receives little psychological treatment. Results suggest that this easily accessible intervention may be effective in improving self-esteem and reducing depression symptoms.

Advances in immersive virtual reality interventions for mental disorders: A new reality?

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.

Virtual Reality Aggression Prevention Therapy (VRAPT) versus Waiting List Control for Forensic Psychiatric Inpatients: A Multicenter Randomized Controlled Trial.

Many forensic psychiatric inpatients have difficulties regulating aggressive behavior. Evidence of effective aggression treatments is limited. We designed and investigated the effectiveness of a transdiagnostic application of a virtual reality aggression prevention training (VRAPT). In this randomized controlled trial at four Dutch forensic psychiatric centers, 128 inpatients with aggressive behavior were randomly assigned to VRAPT (N = 64) or waiting list control group (N = 64). VRAPT consisted of 16 one-hour individual treatment sessions twice a week. Assessments were done at baseline, post-treatment and at 3-month follow-up. Primary outcome measures were aggressive behavior observed by staff and self-reported aggressive behavior. Analysis was by intention to treat. This trial was registered in the Dutch Trial Register (NTR, TC = 6340). Participants were included between 1 March 2017, and 31 December 2018. Compared to waiting list, VRAPT did not significantly decrease in self-reported or observed aggressive behavior (primary outcomes). Hostility, anger control, and non-planning impulsiveness improved significantly in the VRAPT group compared to the control group at post-treatment. Improvements were not maintained at 3-month follow-up. Results suggest that VRAPT does not decrease aggressive behavior in forensic inpatients. However, there are indications that VRAPT temporarily influences anger control skills, impulsivity and hostility.

Virtual reality based cognitive behavioral therapy for paranoia: Effects on mental states and the dynamics among them.

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, posttreatment 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.

To continue or not to continue? Antipsychotic medication maintenance versus dose-reduction/discontinuation in first episode psychosis: HAMLETT, a pragmatic multicenter single-blind randomized controlled trial.

BACKGROUND: Antipsychotic medication is effective for symptomatic treatment in schizophrenia-spectrum disorders. After symptom remission, continuation of antipsychotic treatment is associated with lower relapse rates and lower symptom severity compared to dose reduction/discontinuation. Therefore, most guidelines recommend continuation of treatment with antipsychotic medication for at least 1 year. Recently, however, these guidelines have been questioned as one study has shown that more patients achieved long-term functional remission in an early discontinuation condition-a finding that was not replicated in another recently published long-term study. METHODS/DESIGN: The HAMLETT (Handling Antipsychotic Medication Long-term Evaluation of Targeted Treatment) study is a multicenter pragmatic single-blind randomized controlled trial in two parallel conditions (1:1) investigating the effects of continuation versus dose-reduction/discontinuation of antipsychotic medication after remission of a first episode of psychosis (FEP) on personal and social functioning, psychotic symptom severity, and health-related quality of life. In total 512 participants will be included, aged between 16 and 60 years, in symptomatic remission from a FEP for 3-6 months, and for whom psychosis was not associated with severe or life-threatening self-harm or violence. Recruitment will take place at 24 Dutch sites. Patients are randomized (1:1) to: continuation of antipsychotic medication until at least 1 year after remission (original dose allowing a maximum reduction of 25%, or another antipsychotic drug in similar dose range); or gradual dose reduction till eventual discontinuation of antipsychotics according to a tapering schedule. If signs of relapse occur in this arm, medication dose can be increased again. Measurements are conducted at baseline, at 3, and 6 months post-baseline, and yearly during a follow-up period of 4 years. DISCUSSION: The HAMLETT study will offer evidence to guide patients and clinicians regarding questions concerning optimal treatment duration and when to taper off medication after remission of a FEP. Moreover, it may provide patient characteristics associated with safe dose reduction with a minimal risk of relapse. TRIAL STATUS: Protocol version 1.3, October 2018. The study is active and currently recruiting patients (since September 2017), with the first 200 participants by the end of 2019. We anticipate completing recruitment in 2022 and final assessments (including follow-up 3.5 years after phase one) in 2026. TRIAL REGISTRATION: European Clinical Trials Database, EudraCT number 2017-002406-12. Registered 7 June 2017.

Dynamic Interactive Social Cognition Training in Virtual Reality (DiSCoVR) for social cognition and social functioning in people with a psychotic disorder: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Problems in social functioning (e.g., unemployment, social isolation), are common in people with a psychotic disorder. Social cognition is a treatment target to improve social functioning, as it is a proximal predictor of social functioning. Social Cognition Training (SCT) improves social cognition, but may not generalize (enduringly) to social functioning, perhaps due to insufficient opportunity to practice in daily-life social situations. Using virtual reality (VR) for SCT could address this problem, as VR is customizable, accessible, and interactive. We will test the effect of a VR SCT, 'DiSCoVR', on social cognition and social functioning in a randomized controlled trial (RCT). METHODS: In total 100 people with a psychotic disorder and deficits in social cognition will be recruited for this multicenter randomized controlled trial (RCT). Participants will be randomized to VR SCT (DiSCoVR) or VR relaxation training (VRelax; active control). DiSCoVR is a 16-session individual SCT, consisting of three modules: 1) emotion perception (recognizing facial emotions in a virtual shopping street); 2) social perception and theory of mind (observing social interactions between virtual characters and assessing their behavior, emotions and thoughts); and 3) application of higher-order social cognition in social interaction (role-playing personalized situations in VR). People receiving VRelax complete sixteen individual sessions, in which they receive psycho-education about stress, identify personal stressors, learn relaxation techniques, and explore relaxing immersive virtual environments. Assessments will be performed at baseline, post-treatment, and 3-month follow-up. Primary outcomes are emotion perception (Ekman 60 Faces), social perception and theory of mind (The Awareness of Social Inference Test). Secondary outcomes include social functioning (Personal and Social Performance Scale), experiences and social interactions in daily life (experience sampling of emotions, social participation and subjective experience of social situations), psychiatric symptoms (e.g., depression, perceived stress, anxiety, positive and negative symptoms) and self-esteem. DISCUSSION: To our knowledge, this will be the first RCT testing the efficacy of VR SCT. It will also investigate generalization to daily life social situations, the durability of treatment effects, and moderators and mediators of treatment success. TRIAL REGISTRATION: On December 5, 2017, this trial was registered prospectively in the Dutch Trial Register as NTR6863 .

Virtual reality-based cognitive behavioural therapy for patients with generalized social anxiety disorder: a pilot study.

BACKGROUND: Patients with generalized social anxiety disorder (SAD) avoid various social situations and can be reluctant to engage in in vivo exposure therapy. Highly personalized practising can be required before patients are ready to perform in vivo exposure. Virtual reality-based therapy could be beneficial for this group. AIMS: To assess the feasibility and potential effect of virtual reality-based cognitive behavioural therapy (VR-CBT) for patients with severe generalized SAD. METHODS: Fifteen patients with generalized SAD attended up to 16 VR-CBT sessions. Questionnaires on clinical and functional outcomes, and diary assessments on social activity, social anxiety and paranoia were completed at baseline, post-treatment and at 6-months follow-up. RESULTS: Two patients dropped out of treatment. Improvements in social anxiety and quality of life were found at post-treatment. At follow-up, depressive symptoms had decreased, and the effect on social anxiety was maintained. With respect to diary assessments, social anxiety in company and paranoia were significantly reduced by post-treatment. These improvements were maintained at follow-up. No increase was observed in social activity. CONCLUSIONS: This uncontrolled pilot study demonstrates the feasibility and treatment potential of VR-CBT in a difficult-to-treat group of patients with generalized SAD. Results suggest that VR-CBT may be effective in reducing anxiety as well as depression, and can increase quality of life.

Lack of analgesic effects of transcranial pulsed electromagnetic field stimulation in neuropathic pain patients: A randomized double-blind crossover trial.

BACKGROUND: Neuromodulation is nowadays investigated as a promising method for pain relief. Research indicates that a single 30-minute stimulation with transcranial pulsed electromagnetic fields (tPEMF) can induce analgesic effects. However, it is unknown whether tPEMF can induce analgesia in neuropathic pain patients. OBJECTIVE: To evaluate the effect of tPEMF on spontaneous pain and heat pain in neuropathic pain patients. METHODS: This study had a randomized double-blind crossover design. Twenty neuropathic pain patients received 30-minutes of tPEMF and 30-minutes sham stimulation. Primary outcomes were pain intensity, pain aversion and heat pain. Secondary outcomes included affect, cognition, and motor function, to investigate safety, tolerability and putative working mechanisms of tPEMF. Outcomes were assessed before, during and after stimulation. RESULTS: No differences in analgesic effects between tPEMF and sham stimulation were found for pain intensity, pain aversion or heat pain. No differences between tPEMF and sham stimulation were observed for affect, motor, and cognitive outcomes. CONCLUSION: A single 30-minute tPEMF stimulation did not induce analgesic effects in neuropathic pain patients, compared to sham. Further study is needed to determine whether prolonged stimulation is necessary for analgesic effects.

Virtual-reality-based cognitive behavioural therapy versus waiting list control for paranoid ideation and social avoidance in patients with psychotic disorders: a single-blind randomised controlled trial.

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], p<0·0001; effect size -1·49) and momentary anxiety (-0·288 [-0·438 to -0·1394]; p=0·0002; -0·75) were significantly reduced in the VR-CBT group compared with the control group at the post-treatment assessment, and these improvements were maintained at the follow-up assessment. Safety behaviour and social cognition problems were mediators of change in paranoid ideation. No adverse events were reported relating to the therapy or assessments. INTERPRETATION: 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.

Social environments and interpersonal distance regulation in psychosis: A virtual reality study.

BACKGROUND: Experimentally studying the influence of social environments on mental health and behavior is challenging, as social context is difficult to standardize in laboratory settings. Virtual Reality (VR) enables studying social interaction in terms of interpersonal distance in a more ecologically valid manner. Regulation of interpersonal distance may be abnormal in patients with psychotic disorders and influenced by environmental stress, symptoms or distress. AIMS: To investigate interpersonal distance in people with a psychotic disorder and at ultrahigh risk for psychosis (UHR) compared to siblings and controls in virtual social environments, and explore the relationship between clinical characteristics and interpersonal distance. METHODS: Nineteen UHR patients, 52 patients with psychotic disorders, 40 siblings of patients with a psychotic disorder and 47 controls were exposed to virtual cafés. In five virtual café visits, participants were exposed to different levels of social stress, in terms of crowdedness, ethnicity and hostility. Measures on interpersonal distance, distress and state paranoia were obtained. Baseline measures included trait paranoia, social anxiety, depressive, positive and negative symptoms. RESULTS: Interpersonal distance increased when social stressors were present in the environment. No difference in interpersonal distance regulation was found between the groups. Social anxiety and distress were positively associated with interpersonal distance in the total sample. CONCLUSION: This VR paradigm indicates that interpersonal distance regulation in response to environmental social stressors is unaltered in people with psychosis or UHR. Environmental stress, social anxiety and distress trigger both people with and without psychosis to maintain larger interpersonal distances in social situations.