Multiphase Optimization Strategy (MOST) for Treating Pediatric Post-traumatic Stress Disorder (PTSD)

The CAPS-CA is a clinician-administered interview establishing the presence of a PTSD diagnosis according to DSM-5 diagnostic criteria. The presence of a PTSD diagnosis (yes/no) will be established before and after receiving treatment. Change in PTSD diagnostic status will be used to indicate treatment response.

The CPSS is a child-report survey measuring the severity of PTSD symptoms that will be modified to assess these symptoms in the time since the last treatment session. Survey items assess 20 PTSD symptoms according to DSM-5 diagnostic criteria with severity ratings for each item ranging from 0-4. Ratings for each individual symptom are summed with higher scores indicating greater severities of PTSD symptoms (total scores range from 0-80).

The CATS-2 is a caregiver-reported survey measuring the frequency of pediatric PTSD symptoms that will be modified to assess these symptoms in the time since the last treatment session. Survey items assess 20 PTSD symptoms according to DSM-5 and ICD-11 diagnostic criteria with frequency ratings for each item ranging from 0-3. Ratings for each individual item are summed with higher scores indicating greater frequencies of PTSD symptoms (total scores range from 0-60).

The CDI-2 is a child-report survey assessing the severity of twenty-eight mood disorder symptoms in the past two weeks. Responses are rated on a scale from 0-2 and summed. Higher scores indicate greater severities of mood disorder symptoms (total raw scores range from 0-56). Raw scores can be converted to T-scores.

The SCARED is a child-report survey assessing symptoms of five pediatric anxiety disorders (panic/somatic, generalized anxiety, separation anxiety, social phobia, and school phobia) in the past three months. Responses assess the presence of 41 anxiety symptoms on a scale ranging from 0-2. Item responses are summed with higher scores indicating more severe anxiety symptoms (total scores range from 0-82).

The CBCL is a caregiver-report survey measuring the frequency of child behavior problems in the past six months, including disruptive behavior disorder symptoms. There are 112 items rated on a scale of 0-2 with individual item ratings summed to indicate greater symptom frequency (total scores range from 0-238). Raw scores can be converted to T-scores. The externalizing disorders broadband scale and the DSM-oriented scales will be used to measure disruptive behavior disorder symptoms.

A 29-item, once-daily EMA will be administered to children via smartphone application for a period of two-weeks at pre-treatment, mid-treatment, and post-treatment. Items assess the presence and duration of PTSD, mood, anxiety, and disruptive behavior disorder symptoms on a scale from 0-100. Higher scores indicate a longer duration of symptoms experienced for the day the survey is completed.

The Tasso+ device will be used to obtain whole blood samples. Tasso+ is an FDA 510(k)-approved, sterile, disposable blood lancing device approved for use by laypeople (e.g. caregiver, research staff). A sterile lancet punctures the skin with the press of a button that simultaneously creates a slight vacuum to help capillary blood flow into a compatible tube under gravity. Depending on blood yield, CRP will be assayed.

The Tasso+ device will be used to obtain whole blood samples. Tasso+ is an FDA 510(k)-approved, sterile, disposable blood lancing device approved for use by laypeople (e.g. caregiver, research staff). A sterile lancet punctures the skin with the press of a button that simultaneously creates a slight vacuum to help capillary blood flow into a compatible tube under gravity. Depending on blood yield, IL-6 will be assayed.

The Tasso+ device will be used to obtain whole blood samples. Tasso+ is an FDA 510(k)-approved, sterile, disposable blood lancing device approved for use by laypeople (e.g. caregiver, research staff). A sterile lancet punctures the skin with the press of a button that simultaneously creates a slight vacuum to help capillary blood flow into a compatible tube under gravity. Depending on blood yield, tumor necrosis factor-alpha will be assayed.

MRIs will be performed to measure changes in brain aging, the difference between a participant's chronological age and biological age estimated through several established neural markers. Positive brain aging scores indicate faster brain aging. Negative brain aging scores indicate slower brain aging.

MRIs will be performed to measure changes in neural structures (e.g. hippocampal and amygdala volume) involved in memory retrieval as well as threat and fear processing associated with PTSD and treatment of PTSD.

MRIs will be performed to measure changes in network connectivity (e.g. default mode network) related to working memory performance, autobiographical recall, and fear processing.

The AFQ-Y is a 17-item child report survey assessing experiential avoidance in the presence of aversive private stimuli. Items are anchored on a 0-4 scale with responses summed to indicate greater levels of avoidance (total scores range from 0-68).

The CPTCI is a 25-item measure assessing the presence of different cognitions that may occur following exposure to pediatric trauma. Each item is ranked on a 1-4 scale with individual responses summed to indicate a greater number of trauma-related cognitions (total scores range from 25-100).

Subjects rate the likelihood that a person would transition between two hypothetical affective states. In each trial, subjects are presented with two states connected by an arrow (e.g. happy - angry) and are informed that the state to the left of the arrow is the person's current state and the state on the right side of the arrow is a state the person might experience next. The states included are: hate, love, happy, hurt, mad, sad, scared, and tired. Subjects then rate the likelihood of that person making that transition on a continuous scale from 0-100% with higher scores indicating a greater likelihood of that transition. For a second set of tasks, subjects rate the similarity between each pair of states using a scale from 0-100% with higher ratings indicating greater similarity. Variation in the likelihood ratings for each paired states are examined across participants.

The PQ-BC is a 21-item child-report survey assessing subclinical psychotic symptoms, including unusual beliefs and perceptual distortions in the past month. Each item assesses the presence of a subclinical psychotic symptom in a yes/no response format. A distress score, which weights the endorsed item by the level of distress experienced by that item on a scale of 0-6, is obtained for each of the 21 items. Total scores range from 0-126 with higher scores indicating greater distress.

The K-SADS-CC is a 21-item child-report survey assessing psychiatric symptoms common across different psychiatric disorders. Each item assesses the severity of a psychiatric symptom during the past two weeks on a scale of 0-4. Total scores range from 0-84 with higher scores indicating a greater severity of psychiatric symptoms.

The NIDA mASSIST is a 15-item child-report survey assessing the use of substances. Each item assesses the frequency of use for a specified substance during the past two weeks on a scale of 0-4. Change in the use of individual substances can be examined over time. A polysubstance use severity score can also be generated by summing the frequencies of all individual items. Total scores for the polysubstance use severity score range from 0-84 with higher scores indicating a greater severity of substance use.