Neural connectivity before and after each of the three treatment phases of trauma-focused therapy for adolescent posttraumatic stress

PROJECT SUMMARY 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, we 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. Our 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 our 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, we 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. We will use a randomized controlled trial design to assign participants to either TF-CBT (provided by study team clinicians who meet fidelity standards and receive consultation from Dr. Judith Cohen, the treatment developer) or Treatment as Usual (TAU; provided in the community and does not follow a phased structure). We will collect functional magnetic resonance imaging (fMRI) data 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. We will also identify the phase(s) that best predict end-of-treatment symptom improvement. 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. 1