The study investigates whether a virtual reality-based mindfulness based intervention can reduce impulsive aggression in individuals with schizophrenia or schizoaffective disorder. The primary goal is to evaluate whether mindfulness delivered via VR (MBI-VR) improves emotion regulation and engages the dorsomedial prefrontal cortex (dmPFC), a brain region involved in cognitive control and regulation of emotional responses. The study also examines whether these effects show a dose-related relationship. Participants will be randomized to receive different doses of MBI-VR intervention or distraction tasks and will complete repeated mindfulness VR sessions. Brain activity will be measured using functional magnetic resonance imaging (fMRI) during an emotion regulation task, along with clinical assessments of impulsive aggression related symptoms.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
58
MBI VR is managed through a mobile device management (MDM) solution that supports full access remotely, to ensure the real-time data collection. Research staff members will be available at each session to assist with operational aspects of the MBI VR program (e.g., setting up the VR system, pausing the system if the participant expresses discomfort or distress). MBI delivered via VR is generally considered to be well-tolerated (Dascal et a., 2017); therefore, we do not expect any significant adverse events to occur. However, any seasickness-type of sensation can last for a few hours and even up to a week depending on many factors. While some people rarely experience VR motion sickness, others may continuously suffer symptoms of motion sickness for weeks. The most important factor is the extent of time of uninterrupted exposure. In the present study the exposure is 10 minutes, which is not expected to cause significant VR motion sickness.
Manhattan Psychiatric Center
New York, New York, United States
RECRUITINGNewYork-Presbyterian/Weill Cornell Medical Center Westchester Division
White Plains, New York, United States
RECRUITINGShort UPPS-P Impulsive Behavior Scale
The Short UPPS-P is an instrument composed of 20 items rated on a four-point Likert scale: (1) disagree strongly, (2) disagree some, (3) agree some, and (4) agree strongly. Five scales were computed by adding the 4 items corresponding to each scale: (1) negative urgency (NU), the tendency to act impulsively when experiencing negative emotions (e.g., sadness, anger); (2) positive urgency (PU), the tendency to act rashly under extreme positive emotions or excitement; (3) sensation seeking (SS), the tendency to seek out novel and thrilling experiences, often involving risk; (4) lack of perseveration (PE), the inability to stay focused on a task, especially when it becomes difficult or boring; and (5) lack of premeditation (PR), difficulty thinking and reflecting on the consequences of an act before engaging in it. Each scale ranges from 4 to 16.
Time frame: Will be conducted at Baseline (Day 1), Week 4 (after completion of 16 sessions of MBI-VR or Distraction Tasks), Week 6 (after completion of 24 sessions of MPV-VR or Distraction Tasks)
Impulsive-Premeditated Aggression Scale
The Impulsive-Premeditated Aggression Scale (IPAS; Mathias et al., 2007) will be administered at screening, baseline, after completion of 16 sessions and after completion of 24 sessions. The IPAS is a 30-item self-report questionnaire used to rate aggressive acts occurring over the past six months. Items are scored on a five-point scale (1 = Strongly Disagree; 2 = Disagree; 3 = Neutral; 4 = Agree; 5 = Strongly Agree). The scale differentiates three factors -premeditated aggression, here referred to as 'PM' and impulsive aggression, here referred to as 'IA'-that can be scored either dimensionally or categorically, and Familiarity Items (Stanford MS, Classification procedures, unpublished manual). Discrete categories (impulsive vs premeditated) are obtained by a categorical approach in which only the percentage of the positive items (5 = strongly agree or 4 = agree) for each aggression scale is calculated (Stanford MS, Classification procedures, unpublished manual).
Time frame: Baseline (Day 1), Week 4 (after 16 sessions), Week 6 (after 24 sessions)
Positive and Negative Syndrome Scale
The PANSS will be used to assess psychopathology. The PANSS is a 30-item, clinician-administered assessment that provides scores for positive, negative, and general psychopathology symptoms. The PANSS Excitement Component (PANSS EC; Lindenmayer et al., 2004a; Faay et al., 2018, Lindenmayer et al., 2004b, Montoya et al., 2011) will be examined to assess change in aggressive behaviors. Each PANSS item is scored from 1 to 7, with a minimum score of 30 and a maximum score of 210.
Time frame: Baseline (Day 1), Week 4 (after 16 sessions), Week 6 (after 24 sessions)
Overt Aggression Scale - Modified
Our secondary outcome measure is time to aggressive acts as measured by the Overt Aggression Scale - Modified (OAS-M). The OAS-M is a four-part behavior rating scale used to evaluate and document the "frequency and severity" of aggressive episodes: verbal aggression, aggression against objects, aggression against self, and aggression against others. The OAS-M is a widely used measures for violence and aggression (Mattes, 2010). Each category is rated 0-4 based on severity, with the score multiplied by a weight (1, 2, 3, or 4, respectively) to produce a total weighted score.
Time frame: Baseline (Day 1), Week 4 (after 16 sessions), Week 6 (after 24 sessions)
Clinical Global Impression Aggression Scales
The CGI rating scales are tools used to evaluate both the severity of illness and change from baseline (Guy 1976). The CGI-S Aggression reflects the severity of illness on a 7-point scale ranging from no symptoms (1) to very severe (7). The CGI-I Aggression is used to assess the clinical change as compared to symptoms at baseline using a 7-point scale, ranging from very much improved (1) to very much worse (7).
Time frame: Baseline (Day 1), Week 4 (after 16 sessions), Week 6 (after 24 sessions)
Point Subtraction Aggression Paradigm
The PSAP is a commonly used behavioral aggression paradigm wherein participants earn points (i.e., money) and can steal points from (i.e., aggressive behavior) or have points stolen by an opponent (i.e., provocation), reflecting a more social/non-violent form of reactive aggression. Aggression is scored by counting the number of button presses (e.g., 40, 50, or 100) on a "provocation" button that removes points from the opponent, or by total point subtractions per trial.
Time frame: Baseline (Day 1), Week 4 (after 16 sessions), Week 6 (after 24 sessions)
Quality-of-Life Enjoyment and Satisfaction Questionnaire - Short Form
The QLES-Q-SF will be administered at each study visit to measure patient-assessed health and well-being. This brief, self-report measure is made up of 16 items and is scored using a 5-point Likert scale, and the higher the total score, the more satisfied the patient is with life. The Q-LES-Q-SF (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form) is a 16-item self-report tool where the first 14 items are summed to measure life satisfaction (scores 14-70), with higher scores indicating greater enjoyment. Items use a 5-point Likert scale (1=Very Poor, 5=Very Good). It is converted to a 0-100% scale for interpretation.
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Time frame: Baseline (Day 1), Week 4 (after 16 sessions), Week 6 (after 24 sessions)
Five-facet Mindfulness Questionnaire
The Five-facet Mindfulness Questionnaire (FFMQ; Baer et al., 2006) is a 15 question self-report scale that measures mindfulness with regards to thoughts, experiences, and actions in daily life. The FFMQ-15 measures 5 subscales of mindfulness: Observing, Describing, Acting with Awareness, Non-judgement, and Non-reactivity. The FFMQ will only be completed by participants who are assigned to the MBI VR Group. The self-report scale scored on a 1-5 Likert scale (1=Never true, 5=Very often true). It measures five facets of mindfulness by summing item scores, with some items reverse-scored to indicate higher mindfulness with higher total scores.
Time frame: Baseline (Day 1), Week 4 (after 16 sessions), Week 6 (after 24 sessions)
Number of PRN Medications Issued for Aggressive Behavior
The metric measures the total count of "pro re nata" (PRN) or "as needed" medications administered to a patient in response to acts of physical violence, verbal aggression, or extreme agitation. It is used to monitor behavioral stability, evaluate the effectiveness of non-pharmacological interventions, and ensure safety against over-sedation or misuse.
Time frame: 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
Aggressive incidents will be collected from hospital medical records. Types of Aggressive Incidents 1. Verbal Aggression: including yelling, cursing, threats of violence, and sexual harassment. 2. Physical Assaults: These involve direct contact, such as hitting, kicking, punching, pushing, scratching, spitting, and biting. 3. Other Incidents: This category includes damage to hospital property, armed incidents (such as guns or knives brought into the emergency department), and stalking.
Time frame: 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.