Threat Interpretation Bias as Cognitive Marker and Treatment Target in Pediatric Anxiety

Not Applicable

Completed

Conditions: Anxiety Disorders

Interventions: Other: Cognitive Bias Modification for Interpretations (CBM-I)
Other: Interpretation Control Condition (ICC)

Registration Number: NCT04245501

Lead Sponsor: University of Denver

Brief Summary: Anxiety is the most common mental health problem in children and adolescents. This two-phased study will test the effects of an experimental computerized intervention aimed at reducing threat-based thinking (i.e., interpretation bias) in anxious youth. Participants in both the R61 (N=46) and R33 (N=72) trials will be youth ages 10 to 17 with a primary anxiety disorder (Separation, Social, Generalized). In the R61 trial, youth will be randomly assigned to receive 16 sessions over 4 weeks of either a personalized cognitive bias modification program for interpretation bias (CBM-I) or a computerized control condition (ICC). If CBM-I reduces interpretation bias significantly more than the ICC, the R33 trial will commence. In the R33, youth will be randomly assigned to either CBM-I or an equal amount of time in a cognitive restructuring intervention, which also aims to reduce threat-based thinking in anxiety. Please note that only the R61 phase of the trial has been completed and currently this record summary only reflects the R61 phase.

Detailed Description: Anxiety is the most common mental health problem in youth, affecting one in four children and adolescents. Unfortunately, evidence-based treatments (pharmacotherapy, cognitive-behavioral therapy) are costly, not widely available, and ineffective for a substantial proportion of youth. In response, experts have called for novel treatments that directly target mechanisms underlying youth anxiety while simultaneously addressing barriers to care (i.e., cost, accessibility). One such promising mechanism is interpretation bias - the inaccurate interpretation of threat from ambiguity. The investigators have previously demonstrated that interpretation bias occurs in over 90% of anxious youth, is predictive of anxiety severity in clinical samples of youth, and differentiates between anxious and non-anxious youth. These data indicate that interpretation bias may be a ubiquitous phenomenon underlying anxiety expression in children and adolescents and therefore may be an ideal intervention target. Cognitive bias modification for interpretation bias (CBM-I) is a computerized intervention that attempts to reduce anxiety by directly modifying interpretation bias. CBM-I has demonstrated preliminary efficacy for reducing anxiety symptoms in adults. Yet extant CBM-I data in anxious youth are sparse, with little work addressing whether CBM-I significantly reduces interpretation bias, and whether this in turn reduces anxiety symptoms, as well as the dose necessary to reduce both bias and anxiety. This two-phased study tests personalized CBM-I in youth ages 10 to 17 who meet diagnostic criteria for a primary anxiety disorder (Separation, Social, Generalized). In the R61 Phase (N=46), a randomized clinical trial (RCT) examines whether CBM-I personalized to youth anxiety symptoms significantly reduces interpretation bias compared to a computerized interpretation control condition (ICC). The interpretation target will be measured at multiple time points (4, 8, 12, 16 sessions) to identify the optimal dose for reduction in interpretation bias. If the R61 trial results indicate that CBM-I outperforms ICC on interpretation bias reduction, the R33 phase will commence. In the R33 Phase, an RCT (N=72) will validate whether CBM-I significantly reduces interpretation bias, and conducts a mechanism test (i.e., does bias reduction precede and predict anxiety reduction?), by comparing CBM-I to cognitive restructuring, a clinically relevant psychosocial intervention that also targets anxious cognition. Please note that only the R61 phase of the trial has been completed and currently this record summary only reflects the R61 phase. If the R33 phase is funded, it will be registered as a separate NCT.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 50

Inclusion Criteria

youth aged 10 to 17
diagnosed at study baseline with a primary "big three" anxiety disorder (Separation, Social, Generalized)
standard score greater than or equal to 85 on the Wide Range Achievement Test - Word Reading Subtest (to ensure ability to read stimuli during interpretation bias assessment and CBM-I/ICC), and estimated IQ standard score of at least 80 on the Wechsler Abbreviated Scale of Intelligence
youth and consenting parent/legal guardian speak sufficient English to complete consent/assent and study procedures
no concurrent psychosocial services during study participation to reduce likelihood that other interventions are responsible for change in primary or secondary outcomes
no psychotropic medications with no plans to start medications during study, or six weeks stable on SSRI or psychostimulant medication and dose with no plans to change medication/dose during study

Exclusion Criteria

severe anxiety indicting that youth requires higher level of care (e.g., intensive treatment such as psychiatric hospitalization), significant diagnostic comorbidity (e.g., presence of psychosis or significant mood disorder), or another primary diagnosis that warrants alternate intervention
significant uncorrected vision impairment (e.g., uncorrected blindness) that precludes participation in CBM-I/ICC
safety concerns due to recent or acute suicidality with plan, intent, and/or attempt that warrants alternate intervention

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cognitive Bias Modification for Interpretations (CBM-I)	Cognitive Bias Modification for Interpretations (CBM-I)	Computerized 16-session intervention aimed at reducing interpretation bias. In this study, CBM-I is personalized to youth anxiety symptoms. During CBM-I sessions, youth indicate whether word-sentence pairs are related, and are provided with feedback aimed to reduce bias.
Interpretation Control Condition (ICC)	Interpretation Control Condition (ICC)	Computerized 16-session intervention that is not believed to significantly modify bias. In this study, youth see stimuli personalized to their anxiety symptoms. During ICC sessions, youth see word-sentence pairs and are required to indicate whether word and sentence are related, but are not provided with feedback that aims to "train" a reduction in interpretation bias.

Primary Outcome Measures

Name	Time	Method
Change in Linguistic Interpretation Bias as Assessed by the Word-sentence Association Paradigm for Youth (WSAP-Y)	6 weeks; post-intervention time point	The WSAP-Y is a computerized assessment of interpretation bias in which youth indicate whether word-sentence pairings are related. This measure provides information about the degree to which youth evidence interpretation bias, as well as a behavioral (reaction time) index for bias endorsement. For the primary outcome of percent threat interpretations endorsed, the possible range is 0 (zero) to 100%. Higher percentage indicates more threat interpretation bias (i.e., the youth endorsed a higher proportion of threat words as related to amiguous sentences); lower scores indicate lower threat interpretation bias. Greater decrease in the percent of threat interpretations endorsed and lower absolute scores indicate "better" outcome (i.e., more reduction in threat interpretation bias; less interpretation bias overall).
Change in Visual Interpretation Bias as Assessed by the Ambiguous Faces Task	6 weeks; post-intervention time point	Youth view faces portraying neutral expressions or subtle emotional expressions (i.e., morphed faces ranging in intensity of emotional valence). Youth categorization of faces as neutral or threatening provides their sensitivity and bias for reporting presence of threat. The criterion mean value in outcomes below reflects a score from -1 to 1, with higher negative numbers reflecting greater bias toward angry faces, and higher positive values approaching one reflecting a bias toward happy faces. Theoretically, higher positive values indicate "better" outcome such that youth have more positive bias toward facial stimuli. H
Change in Self-reported Interpretation Bias as Measured by the Children's Automatic Thoughts Scale (CATS)	6 weeks; post-intervention time point	The Children's Automatic Thoughts Scale is a youth self-report questionnaire which assesses presence and frequency of a variety of anxious thoughts from domains of: physical threat, social threat, personal failure, and anxious hostility. Total scores range from 0 to 160, with higher scores indicating more threat interpretation bias. Higher scores indicate "worse" outcome, or that youth self-report that they have more threatening thoughts and/or threatening thoughts at higher frequency; lower scores indicate "better" outcome or that youth self-report fewer threatening thoughts and/or threatening thoughts at lower frequency.

Secondary Outcome Measures

Name	Time	Method
Number of Trainings Completed of 16 Intended Sessions	6 weeks; post-intervention time point	This outcome is related to the "feasibility of CBM-I" aim. The number of CBM-I/ICC trainings completed of 16 intended sessions. Theoretically, completion of more training sessions is better and indicates that youth received a higher "dose" of training.
Participant/Parent Acceptability Questionnaire (PAQ)	6 weeks	The Participant Acceptability Questionnaire is a 10-item youth and parent report questionnaire, accompanied by an exit interview, that assesses burden (travel, boredom), credibility of computerized intervention techniques, and youth comprehension of the intervention. Parents and youth completed the PAQ separately.