A Virtual Reality Mindfulness Application for Aggression in Schizophrenia

This is a randomized, parallel-group, multicenter clinical trial designed to evaluate the effects of a mindfulness-based virtual reality intervention (MBI VR) on impulsive aggression and associated neural target engagement in individuals with schizophrenia or schizoaffective disorder. The study compares two different doses of MBI VR (16 sessions vs. 24 sessions) to a non-immersive Distraction Techniques control condition. Neural target engagement is assessed via functional magnetic resonance imaging (fMRI), with a focus on activation of the dorsomedial prefrontal cortex (dmPFC) during an emotion regulation task.

Screening and Baseline Procedures

Potential participants are identified through a structured pre-screening process involving review of electronic and paper medical records to assess demographic eligibility, psychiatric diagnosis, aggression history, medication adherence, and medical suitability for MRI procedures. Individuals meeting preliminary eligibility criteria are approached for informed consent.

At the Screening Visit, participants undergo diagnostic confirmation using the SCID-5-RV, assessment of suicide risk using the Columbia-Suicide Severity Rating Scale (C-SSRS Baseline), review of medication adherence, and evaluation of impulsive aggression history using the Impulsive-Premeditated Aggression Scale (IPAS). Inclusion and exclusion criteria are confirmed through clinical interview, collateral information, and medical record review.

Eligible participants complete baseline clinical and behavioral assessments, including measures of aggression, impulsivity, psychopathology, mood, anxiety, quality of life, and mindfulness (as applicable). Baseline plasma antipsychotic levels are obtained to assess medication adherence and reduce pharmacologic confounding. Participants also complete a baseline fMRI scan at the Nathan S. Kline Institute for Psychiatric Research.

Randomization and Study Arms

Following completion of baseline procedures, participants are randomized using a stratified randomization approach to ensure balance across treatment arms and study sites. Participants are assigned to one of the following groups:

Mindfulness-Based Intervention Virtual Reality (MBI VR) Distraction Techniques Control

All participants receive up to 24 sessions of their assigned intervention. Neuroimaging and clinical assessments are conducted at baseline, after completion of 16 sessions, and after completion of 24 sessions.

Mindfulness-Based Intervention Virtual Reality (MBI VR)

Participants randomized to the MBI VR group engage in guided mindfulness sessions delivered via the TRIPP™ virtual reality platform using a head-mounted display (Meta Quest 3). Each session lasts approximately 10 minutes and is conducted under supervision of trained research staff.

At the beginning of each session, participants rate their current mood and anxiety using the Oxford Daily Mood Scale (OMS) and State-Trait Anxiety Inventory (STAI). These assessments are administered within the VR environment, with selections made using gaze-based interaction.

The TRIPP MBI VR experience places participants in immersive, computer-generated environments designed to promote relaxation, attentional focus, and emotional awareness. Environments consist of visually dynamic and abstract landscapes, light-based effects, and immersive spatial audio rather than realistic scenes. Guided mindfulness exercises are delivered by a virtual instructor and include breathing awareness, focused attention, body awareness, visualization meditation, and nonjudgmental observation of thoughts and emotions.

Participants are prompted to synchronize breathing with visual cues (e.g., expanding and contracting shapes), reinforcing interoceptive awareness and attentional regulation. Interactive elements are incorporated to enhance engagement while maintaining a non-competitive, exploratory experience. Ambient soundscapes and music are used to support relaxation and sustained attention.

At the conclusion of each session, participants again complete the OMS and STAI to assess immediate changes in mood and anxiety. Participants are encouraged to reflect briefly on their experience, similar to reflective components used in non-VR mindfulness interventions.

All VR sessions are managed via a mobile device management system that allows real-time monitoring and data collection. Research staff remain present to assist with equipment setup and to pause or discontinue sessions if participants experience discomfort or distress.

Distraction Techniques Control Condition

Participants randomized to the Distraction Techniques group engage in non-immersive distraction activities for approximately 10 minutes per session over the same 6-week period. Activities include listening to music, viewing images, or watching brief video clips selected to be engaging but not mindfulness-based.

Participants in this group receive treatment as usual (TAU) in the inpatient setting, including standard rehabilitative programming. The Distraction Techniques condition is designed to control for time, attention, and engagement while isolating the specific effects of immersive mindfulness training delivered via VR.

Functional Magnetic Resonance Imaging (fMRI)

All participants undergo fMRI scanning at three time points: baseline, after 16 sessions, and after 24 sessions. Scans are conducted at the Nathan S. Kline Institute for Psychiatric Research using a 3T Siemens Tim Trio scanner with a 32-channel head coil.

During each scan, participants complete a validated emotion regulation task adapted from Foti and Hajcak (2008). The task involves viewing neutral and unpleasant images from the International Affective Picture System (IAPS), preceded by auditory descriptions that either encourage emotional reactivity or cognitive reappraisal. Participants practice the task outside the scanner prior to imaging to ensure comprehension.

The primary contrast of interest compares unpleasant images preceded by negative versus neutral descriptions, providing an index of emotion regulation. Activation of the dorsomedial prefrontal cortex (dmPFC) during this contrast serves as the primary neural target engagement outcome.

Participants are not scanned within 24 hours of receiving PRN medications to minimize sedation effects. Transport to imaging sessions is conducted with hospital and research staff accompaniment to ensure safety.

Clinical and Behavioral Assessments

Clinical assessments are conducted at screening, baseline, weekly during the intervention period, and at post-intervention time points. Assessments include clinician-rated measures of aggression, psychopathology, and global clinical change, as well as self-report measures of impulsivity, mood, anxiety, quality of life, and mindfulness (MBI VR group only).

Aggression-related assessments include the IPAS, S-UPPS-P, OAS-M, PANSS (including PANSS Excitement Component), CGI-S and CGI-I Aggression, Point Subtraction Aggression Paradigm (PSAP), and real-world behavioral data (e.g., incidents, PRN use, restraints). Suicide risk is monitored throughout the study using the C-SSRS.

Raters conducting aggression and psychopathology assessments are blinded to treatment assignment. Wherever possible, the same rater evaluates a participant throughout the study to reduce inter-rater variability.

Safety Monitoring and Tolerability

Adverse events, including simulator sickness and distress related to VR exposure, are monitored throughout the study. The Simulator Sickness Questionnaire (SSQ) is administered following VR exposure. A score of ≥30 on the SSQ is considered indicative of intolerance and constitutes a criterion for withdrawal from VR participation.

Participants may discontinue participation at any time without impact on their standard psychiatric care. All participants continue to receive treatment as usual for schizophrenia or schizoaffective disorder throughout the study.

• Overt Aggression Scale - Modified [Срок оценки: Baseline (Day 1), Week 4 (after 16 sessions), Week 6 (after 24 sessions)]
• Clinical Global Impression Aggression Scales [Срок оценки: Baseline (Day 1), Week 4 (after 16 sessions), Week 6 (after 24 sessions)]
• Point Subtraction Aggression Paradigm [Срок оценки: Baseline (Day 1), Week 4 (after 16 sessions), Week 6 (after 24 sessions)]
• Quality-of-Life Enjoyment and Satisfaction Questionnaire - Short Form [Срок оценки: Baseline (Day 1), Week 4 (after 16 sessions), Week 6 (after 24 sessions)]
• Five-facet Mindfulness Questionnaire [Срок оценки: Baseline (Day 1), Week 4 (after 16 sessions), Week 6 (after 24 sessions)]
• Number of PRN Medications Issued for Aggressive Behavior [Срок оценки: The number of PRN medications will be collected from 3 months prior to Baseline (Day 1), Week 1, Week 2, Week 3, Week 4, Week 5, Week 6.]
• Number and Type of Aggressive Incidents [Срок оценки: Number and Type of Assaultive Incidents will be collected 3 months prior to Baseline (Day 1), Baseline (Day 1), Week 1, Week 2, Week 3, Week 4, Week 5, Week 6.]