Neural Connectivity During Therapy for Adolescent PTSD

Neural Connectivity Before and After Each of the Three Treatment Phases of Trauma-focused Therapy for Adolescent Posttraumatic Stress

Posttraumatic stress disorder in adolescence impairs neurobiological networks underlying cognitive, social and emotional skills. Neuroimaging research that seeks to identify the neural mechanisms of treatments for PTSD could lead to novel treatments, but progress has been slow using current methods. The proposed study uses an innovative approach to identify neural mechanisms of specific phases of trauma-focused therapy for youth with PTSD, allowing a new understanding of brain changes associated with the process of therapy.

Study Overview

• Status: Recruiting
• Conditions: Adolescent; PTSD; Psychological Trauma
• Intervention / Treatment: Behavioral: TF-CBT; Behavioral: TAU

Detailed Description

Posttraumatic stress disorder (PTSD) during adolescence negatively impacts brain networks underlying cognitive, social, and emotional function. Early intervention is important for mitigating long-term effects, but about 20% of youth do not improve sufficiently with current approaches. By identifying the neurobiological mechanisms of effective therapies, the investigators facilitate the development of novel or personalized treatment approaches for youth with PTSD. However, there has been limited progress in identifying the neural mechanisms of treatment using neuroimaging, partly because most studies collect neuroimaging data at only baseline and end-of-treatment, which collapses across multiple parts of the therapeutic process. The objective of the proposed study is to take a new approach by identifying neural mechanisms associated with specific phases of trauma therapy for youth with PTSD. The central hypothesis is that each phase produces specific brain changes that reflect the acquisition of skills and experiences occurring during that phase. Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) is evidence-based and widely-used to treat children and adolescents with PTSD. It consists of 3 well-defined phases, providing an opportunity to test hypotheses with neuroimaging: changes in executive control networks will occur during the skills phase, changes in limbic networks during the narrative phase, and changes in default mode networks during the consolidation phase. To test these hypotheses, the investigators will recruit N=180 girls and boys, ages 12-17, who have PTSD following interpersonal trauma, such as physical abuse, sexual abuse, or witnessing violence. A randomized controlled trial design will be used to assign participants to either Trauma-focused Cognitive Behavioral Therapy (TF-CBT; provided by study team clinicians who meet fidelity standards) or Treatment as Usual (TAU; provided in the community and does not follow a phased structure). Functional magnetic resonance imaging (fMRI) data will be collected before and after each of the 3 phases of TF-CBT or the same time intervals of TAU. Individual differences in age, sex, dissociative subtype, symptom severity and other variables will be investigated as covariates of phase-related neural changes. Analyses will identify the phases of TF-CBT for which brain regions and networks change for the TF-CBT but not the TAU group. The phase(s) that best predict end-of-treatment symptom improvement also will be identified. Exploratory analyses will use neuroanatomical and white matter diffusivity scans to identify co-occurring changes in brain structure. The proposed innovative study will provide novel information on the neurobiological and cognitive mechanisms associated with the process of trauma therapy for youth with PTSD.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amy Garrett, PhD; Phone Number: 12105678189; Email: garrettas@uthscsa.edu
• Study Contact Backup: Name: Natalia Gomez-Giulilani; Phone Number: 2105678016; Email: gomezgiulian@uthscsa.edu

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • UT Health Department of Psychiatry
      • Contact: Amy Garrett, PhD; Phone Number: 2105678189; Email: garrettas@uthscsa.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ages 12-17 and Tanner stage 2 or above
• history of interpersonal trauma
• PTSD symptoms with a rating of '2' or higher on at least one symptom from each of the 4 clusters, using the Clinician-Administered PTSD Scale for Children and Adolescents, and having a duration of at least one month

Exclusion Criteria:

• current or past use of psychiatric medications
• severe suicidal/homicidal ideation
• current hospitalization
• other current psychotherapy or previous treatment with TF-CBT
• history of head injury with loss of consciousness for >5 minutes
• IQ<85
• major medical illness
• MRI contraindications (metal in body; braces on teeth)
• psychosis, bipolar 1, autism, developmental disorder, panic disorder
• first-degree family member with diagnosis of psychosis or bipolar I disorder
• substance dependence within the past 3 months or current drug use that is frequent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trauma-focused cognitive behavioral therapy (TF-CBT); Trauma-focused Cognitive Behavioral Therapy (TF-CBT) is an evidence-based psychotherapy that is considered the gold-standard treatment for trauma in youth. The TF-CBT model is flexible but it follows a specific order of phases and components, including psychoeducation, emotion regulation skills, processing the trauma narrative, and safety planning. Sessions are provided weekly for 18-weeks.	Behavioral: TF-CBT; evidence-based psychotherapy for trauma in youth
Active Comparator: Treatment As Usual (TAU); Treatment as usual (TAU) consists of the standard-of-care psychotherapy as provided by licensed clinicians at a local clinic. The order and choice of techniques is based on the knowledge and preferences of the clinicians. Sessions are provided weekly for 18-weeks.	Behavioral: TAU; treatment as usual

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean intensity within functional connectivity map of intrinsic network	functional MRI scans will be used to assess neural connectivity	week 0 (baseline)
Mean intensity within functional connectivity map of intrinsic network	functional MRI scans will be used to assess neural connectivity	week 6
Mean intensity within functional connectivity map of intrinsic network	functional MRI scans will be used to assess neural connectivity	week 12
Mean intensity within functional connectivity map of intrinsic network	functional MRI scans will be used to assess neural connectivity	week 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician Administered PTSD Scale - children and adolescents (CAPS-CA)	interview to assess for frequency and severity of PTSD symptoms during the past week	Baseline to week 18

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Amy Garrett, PhD, University of Texas Health Science Center San Antonio

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2022
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: June 10, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 9, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: trauma; neuroimaging; adolescent; psychotherapy
• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Psychological Trauma; Wounds and Injuries; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: HSC20220498H; R01MH127216 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The data sharing plan and reporting of milestones will conform to all preferred NIMH guidelines, as detailed in the NDA Data sharing terms and conditions. Global unique identifiers (GUIDs) will be generated for each study subject. Data will be submitted to NDA every 6 months. We will provide a data submission agreement. The NDA validation tool will be used frequently. The clinical trial protocol also will be submitted as additional information for every collection. Progress reports will include a statement on the progress of data sharing.

1. Summary of data to be shared:

   neuroimaging, clinical, demographic, phenotypic, neuropsychological

2. Description of the data dictionaries used to describe the data set:

   Axis 1 diagnoses, CDI, CAPS-CA, fMRI behavior, beta weights, network correlations

3. Proposed schedule to validate that the data are compliant with the data dictionary:

Data will be validated on a quarterly basis

• IPD Sharing Time Frame: Immediately following publication. No end date.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No