Neural Correlates of Symptom Reduction During TF-CBT JOSH CISLER, PHD BRAIN IMAGING RESEARCH CENTER PSYCHIATRIC RESEARCH INSTITUTE UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES

Overview Discuss a recent collaborative study between AR BEST and BIRC to understand treatment response to TF-CBT ◦Participants were local Arkansan adolescent girls with PTSD related to assault ◦Many of the participants were even referred to us by AR BEST clinicians Purpose of the study What the study involved Results and some preliminary conclusions

What is TF-CBT? Trauma-focused cognitive behavioral therapy – structured psychological therapy targeting the following domains: ◦Psychoeducation and Parenting ◦Relaxation ◦Affect Modulation ◦Cognitive Coping Skills ◦Trauma Narrative / Cognitive Processing ◦In vivo exposure ◦Conjoint parent-child sessions ◦Enhancing future safety Typically delivered in sessions Strong evidence base for traumatized children with PTSD, anxiety, depression, or externalizing behaviors related to trauma exposure

Purpose of the Study TF-CBT is our gold-standard treatment for youth with traumatic stress-related symptoms Nonetheless, 100% symptom reduction does not always occur

From Cohen et al – randomized controlled trial of TF-CBT in a community setting On average, children after TF-CBT still demonstrated significant PTSD symptoms

Purpose of the Study TF-CBT is our gold-standard treatment for youth with traumatic stress-related symptoms Nonetheless, 100% symptom reduction does not always occur Our overall goal is to understand how to improve the consistency of response to TF-CBT ◦1) Can we identify pre-treatment markers of who will response best? ◦2) can we identify the mechanisms through which TF-CBT works so that we can learn how to enhance it?

Study Overview Recruited adolescent girls, aged 11-17, with PTSD related to physical or sexual assault Provided 12 sessions of manualized TF-CBT ◦Thanks to Drs. Karin Vanderzee, Joy Pemberton, and Ben Sigel!!!! ◦Followed standard PRACTICE modules Assessed clinical symptoms before and after treatment Assessed brain function before and after treatment ◦Functional magnetic resonance imaging (fMRI) ◦Measure brain activity while the adolescent performs a cognitive task

Enrollment Flow

Fearful expressionNeutral expression Emotion Processing Task

Participant gets an instruction: ‘notice your feeling’ or ‘think positive’ Then they see either a negative image or a neutral image Cognitive re-appraisal task

Participant gets an instruction: ‘notice your feeling’ or ‘think positive’ “the building wasn’t safe so they are taking it down to build a safer one”

Variable Mean/frequenc y (SD) Age13.87 (1.77) Verbal IQ95.26 (15.00) Ethnicity 39% Caucasian 52% African American 9% Biracial 0% Hispanic Total number of types of assaults 5.65 (3.98) Direct Physical Assault96% Sexual Assault87% Witnessed Violence91% Psychotropic Medication SSRI - 39% Antipsychotic – 17% SARI – 4% Alpha blocker – 4% Pre-Treatment Post- Treatment Current PTSD100%35% # comorbid diagnoses2.74 (2.22)1.00 (1.62) Current Anxiety Disorder65%17% Current Depressive Disorder 52%13% Current Bipolar Disorder4%0% Current Alcohol Use (past year) 8%4% Current Substance Use (past year) 12%17% Current Conduct/ODD26%21% UCLA PTSD Index36.04 (17.87)18.30 (16.62) SMFQ12.22 (8.25)4.61 (6.55)

Who is likely to be a good responder to TF-CBT? Can we identify markers that let us predict who will and will not have good responses to TF-CBT?

Who is likely to be a good responder to TF-CBT? Can we identify markers that let us predict who will and will not have good responses to TF-CBT? ◦Using data from the emotion processing task ◦Does pre-treatment brain activity to emotional images predict symptom reduction?

Who is likely to be a good responder to TF-CBT? Adolescent girls who differentiate danger from safety signals seem to be more likely to respond better to TF-CBT

What are the mechanisms of TF- CBT? Through what intermediate mechanisms does TF-CBT produce symptom change?

Penicillin Fever reduction

Penicillin Fever reduction Infection reduction

TF-CBT PTSD symptom reduction

TF-CBT PTSD symptom reduction ??????

TF-CBT PTSD symptom reduction Emotion Regulation

What are the mechanisms of TF- CBT? TF-CBT may improve the adolescent’s ability to regulate emotions, which results in PTSD symptom reductions Better emotion regulation may be due to specific brain changes: ◦Suppression of amygdala-insula functional connectivity ◦Heightened amygdala-dACC functional connectivity appears to be detrimental

Overall Discussion There is significant variability in PTSD symptom reduction during TF-CBT ◦Partly related to initial symptom severity ◦Partly related to how well the adolescent initially discriminates danger from safety ◦Partly related to how well TF-CBT helps the child learn to regulate emotions ◦Which is partly related to specific changes in brain function during emotion regulation

Overall Discussion There is significant variability in PTSD symptom reduction during TF-CBT ◦Partly related to initial symptom severity ◦Partly related to how well the adolescent initially discriminates danger from safety ◦Partly related to how well TF-CBT helps the child learn to regulate emotions ◦Which is partly related to specific changes in brain function during emotion regulation

Limitations Small sample (N=25) Only girls Only 12 sessions ◦Allows comparability across adolescents, but real-world TF-CBT can be more flexible Long-term follow-up?

We are recruiting for more research studies!!! Further investigations of how early life trauma changes brain function and increases risk for ◦Drug use disorders ◦PTSD ◦Risk for revictimization ◦Problems with intimacy and trust

We recruiting for more research studies!!! Adolescent girls age With or without histories of physical or sexual assault With or without histories of drug use No internal metal (no braces) Adolescent and caregiver earn monetary compensation Contact Jennifer Payne: