Exploring the role of clinical and demographic characteristics on the effects of virtual reality cognitive behavioral therapy for psychosis: A moderator analysis.

BACKGROUND: Virtual Reality cognitive behavioral therapy (VR-CBT) has proven to be an effective treatment method for paranoia and anxiety in psychosis. However, it is unknown, which individuals benefit most from VR-CBT. Previous studies examined factors affecting the treatment effect of regular CBTp, including illness duration, paranoia, depression, and pre-therapy avoidance behaviors, but results are inconsistent. The study aims to investigate the factors that influence the effectiveness of VR-CBT. METHODS: A total of 95 participants with a psychotic disorder and at least moderate paranoia (GTPS >40) were included in this explorative study. Data were collected as part of a multicenter randomized controlled trial in which participants were assigned to VR-CBT or treatment as usual (TAU). The VR-CBT group received 16 sessions of individual treatment. A moderator analysis was conducted to examine the influence of baseline demographic (age, gender, and education level) and clinical characteristics (duration of illness, paranoia, anxiety, depression, safety behavior, self-esteem, and social functioning) on treatment effects of paranoia and anxiety as measured with questionnaires and the experience sampling method (ESM) directly after treatment (12 weeks after baseline). RESULTS: More use of safety behavior at baseline resulted in greater benefits of VR-CBT on paranoid ideation and ESM paranoia. A higher age was associated with greater benefits of VR-CBT on social anxiety but not paranoia outcomes. There was no consistent evidence of moderation by any of the other sociodemographic or clinical variables for paranoid ideation and social anxiety. CONCLUSIONS: Our findings suggest that a diverse spectrum of patients, with different backgrounds and symptom severity may be able to benefit from VR-CBT. VR-CBT can be recommended to a broad spectrum of patients with psychotic disorders, and particularly those with high levels of safety behaviors, including severe avoidance, seem to benefit more.

Virtual reality cognitive-behavioural therapy versus cognitive-behavioural therapy for paranoid delusions: a study protocol for a single-blind multi-Centre randomised controlled superiority trial.

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.

Th17/T regulator cell balance and NK cell numbers in relation to psychosis liability and social stress reactivity.

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.

Childhood trauma, psychosis liability and social stress reactivity: a virtual reality study.

BACKGROUND: Childhood 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. METHOD: Seventy-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. RESULTS: Childhood 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. CONCLUSIONS: Childhood 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.

Relations between changes in safety behavior, paranoid ideations, cognitive biases, and clinical characteristics of patients with a psychotic disorder over time.

BACKGROUND: Safety behaviors, both positive (maladaptive coping behavior) and negative (avoidance behavior), are used by people with paranoid delusions to avoid perceived threats. Safety behaviors contribute to the persistence of paranoid delusions by preventing disconfirmation of threat beliefs and may influence other psychiatric symptoms. This study investigated how changes in safety behaviors are related to changes in paranoid ideation, social anxiety, depression, cognitive biases and self-esteem over time. METHODS: This study included 116 patients diagnosed with a psychotic disorder (DSM-IV) and at least moderate levels of paranoid ideations (GTPS >40).The data were collected as part of a multi-center randomized controlled trial where patients were randomized to VR-CBT (n = 58) or treatment as usual (TAU; n = 58). Assessments were completed at baseline (T0), after three months (T3) and after six months (T6). For all variables, change scores between T0 and T3 and T3 and T6 were calculated and Pearson correlations between change scores were computed. RESULTS: A decrease in total safety behavior was related to diminished paranoid ideation, social anxiety, and depression. No significant temporal associations were found between changes in safety behavior and changes in cognitive biases and self-esteem. Similar but less robust results were found for respectively negative safety behavior and positive safety behavior. CONCLUSION: Dropping safety behavior can be specifically targeted in behavioral interventions. Whereas there appears to be a relation with reduction in anxiety, paranoia, and depressive symptoms, changes in safety behavior do not seem to align with changes in cognitive thinking processes.