A Virtual Reality Mindfulness Application for Aggression in Schizophrenia

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.

Study Overview

• Status: Recruiting
• Conditions: Aggression; Schizoaffecitve Disorder; Schizophrenia Disorder
• Intervention / Treatment: Other: Mindfulness-Based Virtual Reality Intervention

Detailed Description

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
• Enrollment (Estimated): 58
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anzalee Khan, PhD; Phone Number: 646-766-5876; Email: anzalee.khan@nki.rfmh.org
• Study Contact Backup: Name: Benedicto Parker; Phone Number: 212-961-8992; Email: Benedicto.Parker@nki.rfmh.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10035
      • Recruiting
      • Manhattan Psychiatric Center
      • Contact: Benedicto Parker; Phone Number: 212-961-8992; Email: Benedicto.Parker@nki.rfmh.org
      • Contact: Naphtali Calliste, MPH; Phone Number: 646-766-5874; Email: naphtali.calliste@nki.rfmh.org
      • Principal Investigator: Anzalee Khan, PhD
    • White Plains, New York, United States, 10605
      • Recruiting
      • NewYork-Presbyterian/Weill Cornell Medical Center Westchester Division
      • Contact: Jewel Bell; Phone Number: 914.682.5404; Email: jeb4018@med.cornell.edu
      • Principal Investigator: Anthony Ahmed, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

TRIPP MBI VR and TAU Distraction Groups have the same inclusion criteria. Participants will:

1. Is willing and able to provide written informed consent to participate in the study, attend study visits, and comply with study-related requirements and assessments.
2. Fluent in written and spoken English, confirmed by ability to read and understand the informed consent form.
3. Be on optimized and stable atypical antipsychotic treatment as indicated by no antipsychotic changes in 2 weeks prior to enrollment.
4. Demonstrate documented evidence of good medication adherence for the 2 weeks prior to enrollment, as determined by electronic medication records review and prescriber reported adherence to prescribed schedule as documented in the participant's medical records.
5. Have a history of impulsive aggression as assessed by a score of ≥ 4 on any item on Impulsive Aggression Factor (IA) on the Impulsive- Premeditated Aggression Scale (IPAS; Stanford et al., 2003).
6. Have adequate visual and auditory abilities to complete assessments, see and hear stimuli in the VR
7. Has a primary diagnosis of schizophrenia using the diagnostic criteria for schizophrenia or schizoaffective disorder, as defined in the SCID-5-RV at the Screening Visit.
8. Adult or late adolescent, between 18 and 64 years of age at the time of informed consent.

Exclusion Criteria:

Participants will be excluded if they:

1. Have past head trauma
2. Diagnosed with a neurological disorder
3. Are pregnant or breastfeeding women as evidenced by the participant's medical record.
4. Have unstable medical illness that compromises the safety of the patient
5. Have significant suicidal ideation at screening (as assessed by the Columbia - Suicide Severity Rating Scale (C-SSRS; participant answers "Yes" to "suicidal ideation" Item 4 (active suicidal ideation with some intent to act, without a specific plan) or Item 5 (active suicidal ideation with a specific plan and intent) on the C-SSRS; Non-suicidal self-injurious behavior is not exclusionary)
6. Are on Electroconvulsive therapy (ECT) within 6 months of the study, participants with metal in their bodies or who have claustrophobia or who do not pass the criteria in NKI's Magnetic Resonance Safety Questionnaire (MRSQ)
7. Score < 4 on all items on Impulsive Aggression Factor (IA) on the IPAS (Stanford et al., 2003)
8. Have a violent episode requiring seclusion, restraints, or a prn within the week before screening
9. Evidence of suboptimal medication adherence in the 2 weeks prior to enrollment, as determined by electronic medication records review, and demonstrated by prescriber reported non- adherence to prescribed schedule. Suboptimal adherence includes missed doses (two of more missed doses within the past 2 weeks) or plasma levels indicating that the participant is not receiving the intended therapeutic dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Mindfulness-Based Virtual Reality (MBI-VR); The MBI VR is developed by TRIPP. Instead of naturalistic scenic images, the TRIPP MBI VR features intricate visually dynamic environments such as colorful surreal landscapes, light-based effects, floating shapes and immersive spatial soundscapes. These visuals encourage participants to focus on flowing designs, fostering a sense of engagement. The game-like quality of the virtual environment includes interactive elements where participants can manipulate shapes or respond to stimuli. This interactivity can enhance engagement, turning mindfulness meditation into a game-like playful and exploratory experience. The TRIPP MBI VR program offers guided sessions led by a virtual instructor, who provides verbal cues and instructions for the practice. This guidance includes breathing techniques, body awareness exercises, or instructions for focusing attention.	Other: Mindfulness-Based Virtual Reality Intervention; 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.
Other: Distraction Tasks; Tasks will include standard rehabilitative inpatient treatment as usual (TAU) which includes wellness and recovery sessions, coping skills, understanding medications, discharge preparation, and behavioral sessions and Distraction Techniques. Distraction Techniques that encompass activities designed to engage participants and divert their attention from discomfort or distressing thoughts. These techniques can include: Listening to Music: Participants may listen to calming or enjoyable music, which can help reduce anxiety and enhance relaxation by promoting positive emotional states.; Viewing Images: Participants may look at carefully selected images or visuals, such as nature scenes, art, or other soothing imagery. This can create a sense of calm and provide a mental escape from their current situation.; Watching Videos: Participants may engage with short videos or clips that are designed to be engaging, aiming to promote distraction and engage their interest.	Other: Mindfulness-Based Virtual Reality Intervention; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short 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.	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).	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.	Baseline (Day 1), Week 4 (after 16 sessions), Week 6 (after 24 sessions)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	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.	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.	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.	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.	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; Verbal Aggression: including yelling, cursing, threats of violence, and sexual harassment.; Physical Assaults: These involve direct contact, such as hitting, kicking, punching, pushing, scratching, spitting, and biting.; Other Incidents: This category includes damage to hospital property, armed incidents (such as guns or knives brought into the emergency department), and stalking.	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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxford Daily Mood Scale (OMS)	The Oxford Daily Mood Scale is a self-assessment tool designed to help individuals quantify their emotional state throughout the day using a simple 10-point scale. This scale allows users to track fluctuations in their mood over time by assigning a score based on how they felt at different points during the day. Scale Description: Very Depressed; Depressed; Somewhat Low; Slightly Low; "So-so"; Slightly Good; Somewhat Happy; Happy; Very Happy	The Oxford Mood Scale is done prior to the start of each MBI VR or Distraction Techniques sessions at Baseline (Day 1), Week 1, Week 2, Week 3, Week 4, Week 5, and Week 6.
Columbia-Suicide Severity Rating Scale Baseline	The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinical tool designed to assess suicide risk, facilitating comprehensive evaluations in both clinical and research settings. Below is an extended description of the scale, its application, and its significance in assessing suicide risk. The C-SSRS aims to: Identify Individuals at Risk: It helps health professionals determine the severity of suicidal ideation and behavior in individuals, enabling timely intervention. Facilitate Management Plans: By quantifying suicide risk, this scale informs treatment planning and follow-up strategies. Standardize Assessments: It provides a structured format for evaluating suicidality, enhancing reliability across different raters and settings.	The C-SSRS Baseline version will be completed at Baseline (Day 1) for all study participants.
Columbia-Suicide Severity Rating Scale Since Last Visit	The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinical tool designed to assess suicide risk, facilitating comprehensive evaluations in both clinical and research settings. Below is an extended description of the scale, its application, and its significance in assessing suicide risk. The C-SSRS aims to: Identify Individuals at Risk: It helps health professionals determine the severity of suicidal ideation and behavior in individuals, enabling timely intervention. Facilitate Management Plans: By quantifying suicide risk, this scale informs treatment planning and follow-up strategies. Standardize Assessments: It provides a structured format for evaluating suicidality, enhancing reliability across different raters and settings.	The C-SSRS Since Last Visit version is completed once a week at Week 1, Week 2, Week 3, Week 4, Week 5, and Week 6.
Simulator Sickness Questionnaire	The Simulator Sickness Questionnaire (SSQ) is a 16-item self-report tool developed by Kennedy et al. (1993) to quantify side effects from virtual environments or flight simulators. It rates symptoms - nausea, oculomotor, and disorientation, on a 0-3 scale, widely used to assess cybersickness in VR. Scores determine overall severity, aiding in identifying problematic simulators. The SSQ measures 16 symptoms (e.g., headache, eyestrain, dizziness, vertigo, nausea) rated by the participant as "None" (0), "Slight" (1), "Moderate" (2), or "Severe" (3). Subscales: Symptoms are grouped into three factors: 1. Nausea (N): General discomfort, increased salivation, sweating, nausea, difficulty concentrating, stomach awareness, burping. 2. Oculomotor (O): General discomfort, fatigue, headache, eyestrain, difficulty focusing, difficulty concentrating, blurred vision. 3. Disorientation (D): Difficulty focusing, nausea, fullness of head, blurred vision, dizziness, vertigo.	The Simulator Sickness Questionnaire is administered after the participant has completed each MBI VR session at each visit (Week 1, Week 2, Week 3, Week 4, Week 5, and Week 6).
Structured Clinical Interview for DSM-5 (SCID-5) - Research Version	The SCID-5-RV (Research Version) is a specialized adaptation of the Structured Clinical Interview for DSM-5 (SCID-5) designed specifically for use in clinical trials. This version has been reformatted, streamlined, and optimized to meet the requirements of clinical research protocols. The SCID-5 is primarily designed to ensure that major psychiatric diagnoses, as outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM- 5), are systematically evaluated.	The SCID-5-RV will be completed at Screening to confirm diagnosis.
Mobile App Rating Scale	The Mobile App Rating Scale (MARS) is a reliable, multidimensional tool designed to assess the quality of mobile health (mHealth) apps across 23 items covering engagement, functionality, aesthetics, information quality, and subjective impact. It uses a 5-point scale (1-inadequate to 5-excellent) to evaluate apps, making it a standard instrument for researchers and developers to ensure high-quality, evidence-based app development. The MARS includes the following dimensions: 1. Assesses apps based on Engagement (fun, interest), 2. Functionality (performance, navigation), 3. Aesthetics (layout, graphics), and 4. Information Quality (accuracy, evidence base).	The MARS is completed at Week 24 or Early Termination Visits.
Antipsychotic Plasma Levels	In order to ascertain medication adherence and to minimize confounding effects of antipsychotic medication treatment, we will measure antipsychotic plasma level at baseline, and after 16 and 24 sessions.	Measurements of antipsychotic plasma level will be taken at Baseline (Day 1), Week 4 and Week 6.
Number of seclusion or restraints related to aggressive behaviors	Seclusion and restraint are last-resort safety measures for imminent, severe aggression or self-injury, not for punishment or convenience. They involve involuntary confinement or physical/mechanical restriction of movement. These practices carry risks of serious injury, trauma, and, in rare cases, fatality, requiring strict, immediate oversight. The number of times a participant was restrained or secluded will be collected.	The number of seclusions and restraints will be collected from 3 months prior to Baseline (Day 1) and at Baseline (Day 1), Week 1, Week 2, Week 3, Week 4, Week 5, and Week 6.
Number and Type of Arrests	"Number and Type of Arrests" measures the volume and nature of law enforcement apprehensions. It will be used to track the total count of crimes committed, as one incident may result in multiple arrests or vice versa. The following will be collected: 1. Total Volume: The aggregate count of all arrests made, 2. Type of Offense (i.e., Group A Offenses: includes violent crimes (homicide, rape, robbery, aggravated assault), property crimes (burglary, larceny, motor vehicle theft, arson), and drug offenses; Group B Offenses: Crimes for which only arrest data are reported, such as disorderly conduct, DUI, drunkenness, and vagrancy).	The number and type of arrests will be collected from 3 months prior to Baseline (Day 1) and at Baseline (Day 1), Week 1, Week 2, Week 3, Week 4, Week 5, and Week 6.

Collaborators and Investigators

• Sponsor: Manhattan Psychiatric Center
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Anzalee Khan, PhD, Nathan Kline Institute for Psychiatric Research; Study Director: Jean-Pierre Lindenmayer, MD, Nathan Kline Institute for Psychiatric Research

Publications and helpful links

General Publications

• Klein Tuente S, Bogaerts S, van IJzendoorn S, Veling W. Effect of virtual reality aggression prevention training for forensic psychiatric patients (VRAPT): Study protocol of a multi-center RCT. BMC Psychiatry. 2018;18(1). doi:10.1186/s12888-018-1830-8
• Hoptman MJ. Impulsivity and aggression in schizophrenia: a neural circuitry perspective with implications for treatment. CNS Spectr., 20 (2015), pp. 280-286.
• Hoptman MJ, Antonius D, Mauro CJ, Parker EM, Javitt DC. Cortical thinning, functional connectivity, and mood-related impulsivity in schizophrenia: relationship to aggressive attitudes and behavior. Am. J. Psychiatry, 171 (2014), pp. 939-948,
• Fritz M, Shenar R, Cardenas-Morales L, Jäger M, Streb J, Dudeck M, Franke I. Aggressive and Disruptive Behavior Among Psychiatric Patients With Major Depressive Disorder, Schizophrenia, or Alcohol Dependency and the Effect of Depression and Self-Esteem on Aggression. Frontiers in Psychiatry, 11, 2020.
• Flores A, Linehan MM, Todd SR, Hoffman HG. The use of virtual reality to facilitate mindfulness skills training in dialectical behavioral therapy for spinal cord injury: A case study. Frontiers in Psychology. 2018;9.
• Farb NAS, Anderson AK, Mayberg H, Bean J, McKeon D, Segal ZV. Minding one's emotions: Mindfulness training alters the neural expression of sadness. Emotion (Washington, DC). 2010;10(1):25-33.
• Davis L, Kurzban S. Mindfulness-based treatment for people with severe mental illness: a literature review. American Journal of Psychiatric Rehabilitation. 2012;15(2):202-232.doi:10.1080/15487768.2012.679578
• Dale AM. Optimal experimental design for event-related fMRI. Human Brain Mapping. 1999;8(2-3):109-114.
• Cutcliffe JR, Riahi S. Systemic perspective of violence and aggression in mental health care: Towards a more comprehensive understanding and conceptualization: Part 1. International Journal of Mental Health Nursing. 2013;22(6):558-567.
• Cohn AM, Jakupcak M, Seibert LA, Hildebrandt TB, Zeichner A. The role of emotion dysregulation in the association between men's restrictive emotionality and use of physical aggression. Psychology of Men & Masculinity. 2010;11(1):53.
• Chadwick P, Hughes S, Russell D, Russell I, Dagnan D. Mindfulness groups for distressing voices and paranoia: A replication and randomized feasibility trial. Behavioural and Cognitive Psychotherapy. 2009;37(4):403-412.
• Brown KW, Ryan RM. The benefits of being present: Mindfulness and its role in psychological well-being. Journal of Personality and Social Psychology. 2003;84(4):822-848.
• Aldao A, Nolen-Hoeksema S, Schweizer S. Emotion-regulation strategies across psychopathology: a meta-analytic review. Clinical Psychology Review. 2010;30:217-237.

Study record dates

Study Major Dates

• Study Start (Estimated): March 2, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: January 22, 2026
• First Submitted That Met QC Criteria: February 20, 2026
• First Posted (Actual): February 25, 2026

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: schizophrenia; emotion regulation; dmPFC; mindfulness based intervention; impulsive aggression
• Additional Relevant MeSH Terms: Aberrant Motor Behavior in Dementia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Social Behavior; Self-Control; Schizophrenia; Aggression; Emotional Regulation
• Other Study ID Numbers: NKI2025-37-MPC; 1R61MH133785 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual Participant Data (IPD) will not be shared to protect participant privacy and confidentiality, given the sensitive nature of the clinical, behavioral, and neuroimaging data collected in this study. The dataset includes detailed mental health assessments, aggression-related measures, and brain imaging data, which pose a risk of re-identification even after de-identification. In addition, participants did not provide consent for broad data sharing beyond the scope of the study. Therefore, to comply with ethical standards, informed consent agreements, and applicable privacy regulations, IPD will not be made publicly available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No