Trial Outcomes & Findings for Threat Interpretation Bias as Cognitive Marker and Treatment Target in Pediatric Anxiety (NCT NCT04245501)

Last Updated: 2025-03-05

Results Overview

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).

Recruitment status

COMPLETED

Study phase

Target enrollment

50 participants

Primary outcome timeframe

6 weeks; post-intervention time point

Results posted on

2025-03-05

Participant Flow

Please note that youth were enrolled in the study and their caregiver completed questionnaires and diagnostic interviews about the youth (not about themselves as caregivers/adults). As such, youth were the only true participants in the study (i.e., this was not dyad recruitment and caregivers did not participate as study participants but as additional reporters on the youths' symptoms as is typical in clinical anxiety trials with child and adolescent participants).

Participant milestones

Participant milestones
Measure	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. Cognitive Bias Modification for Interpretations (CBM-I): Computerized intervention in which youth see word-sentence pairs personalized to their anxiety symptoms, and indicate whether these are related. Youth receive feedback aimed to reduce interpretation bias.	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. Interpretation Control Condition (ICC): Computerized control condition in which youth see word-sentence pairs personalized to their anxiety symptoms. Youth indicate whether these are related, but are not provided with feedback that aims to "train" a reduction in interpretation bias.
Overall Study STARTED	25	25
Overall Study COMPLETED	23	24
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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. Cognitive Bias Modification for Interpretations (CBM-I): Computerized intervention in which youth see word-sentence pairs personalized to their anxiety symptoms, and indicate whether these are related. Youth receive feedback aimed to reduce interpretation bias.	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. Interpretation Control Condition (ICC): Computerized control condition in which youth see word-sentence pairs personalized to their anxiety symptoms. Youth indicate whether these are related, but are not provided with feedback that aims to "train" a reduction in interpretation bias.
Overall Study Adverse Event	2	0
Overall Study ineligible participant unknowingly enrolled	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cognitive Bias Modification for Interpretations (CBM-I) n=25 Participants 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. Cognitive Bias Modification for Interpretations (CBM-I): Computerized intervention in which youth see word-sentence pairs personalized to their anxiety symptoms, and indicate whether these are related. Youth receive feedback aimed to reduce interpretation bias.	Interpretation Control Condition (ICC) n=25 Participants 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. Interpretation Control Condition (ICC): Computerized control condition in which youth see word-sentence pairs personalized to their anxiety symptoms. Youth indicate whether these are related, but are not provided with feedback that aims to "train" a reduction in interpretation bias.	Total n=50 Participants Total of all reporting groups
Age, Continuous	12.76 years STANDARD_DEVIATION 1.64 • n=5 Participants	12.20 years STANDARD_DEVIATION 1.80 • n=7 Participants	12.48 years STANDARD_DEVIATION 1.73 • n=5 Participants
Sex/Gender, Customized Youth self-identified gender · Female	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Sex/Gender, Customized Youth self-identified gender · Male	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Sex/Gender, Customized Youth self-identified gender · Non-binary	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants	20 Participants n=7 Participants	43 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants	19 Participants n=7 Participants	42 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants	25 participants n=7 Participants	50 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks; post-intervention time point

Population: The WSAP-Y analysis was a between-groups analysis of interpretation bias as measured by percent threat interpretations endorsed during the task. The outcome measures data below provides the percent threat interpretations endorsed at the post-treatment (6 weeks) endpoint, and does not reflect the complex linear, quadratic, and piecewise models of change for analyses in Aims 1 and 2.

Outcome measures

Outcome measures
Measure	Cognitive Bias Modification for Interpretations (CBM-I) n=25 Participants 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. Cognitive Bias Modification for Interpretations (CBM-I): Computerized intervention in which youth see word-sentence pairs personalized to their anxiety symptoms, and indicate whether these are related. Youth receive feedback aimed to reduce interpretation bias.	Interpretation Control Condition (ICC) n=25 Participants 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. Interpretation Control Condition (ICC): Computerized control condition in which youth see word-sentence pairs personalized to their anxiety symptoms. Youth indicate whether these are related, but are not provided with feedback that aims to "train" a reduction in interpretation bias.
Change in Linguistic Interpretation Bias as Assessed by the Word-sentence Association Paradigm for Youth (WSAP-Y)	19.77 score on a scale Standard Deviation 19.48	47.40 score on a scale Standard Deviation 13.52

PRIMARY outcome

Timeframe: 6 weeks; post-intervention time point

Population: The faces analysis was a between-groups analysis of interpretation bias as measured using signal detection theory. The analysis was a between-groups analysis of interpretation bias for detecting anger versus happy faces. The outcome measures data below provides the measure endorsed at the post-treatment (6 weeks) endpoint, and does not reflect the complex linear, quadratic, and piecewise models of change for analyses in Aims 1 and 2.

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

Outcome measures

Outcome measures
Measure	Cognitive Bias Modification for Interpretations (CBM-I) n=25 Participants 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. Cognitive Bias Modification for Interpretations (CBM-I): Computerized intervention in which youth see word-sentence pairs personalized to their anxiety symptoms, and indicate whether these are related. Youth receive feedback aimed to reduce interpretation bias.	Interpretation Control Condition (ICC) n=25 Participants 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. Interpretation Control Condition (ICC): Computerized control condition in which youth see word-sentence pairs personalized to their anxiety symptoms. Youth indicate whether these are related, but are not provided with feedback that aims to "train" a reduction in interpretation bias.
Change in Visual Interpretation Bias as Assessed by the Ambiguous Faces Task	0.86 score on a scale Standard Deviation 0.87	1.32 score on a scale Standard Deviation 0.54

PRIMARY outcome

Timeframe: 6 weeks; post-intervention time point

Population: The outcome measures data below provides the measure endorsed at the post-treatment (6 weeks) endpoint, and does not reflect the complex linear, quadratic, and piecewise models of change for analyses in Aims 1 and 2.

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.

Outcome measures

Outcome measures
Measure	Cognitive Bias Modification for Interpretations (CBM-I) n=25 Participants 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. Cognitive Bias Modification for Interpretations (CBM-I): Computerized intervention in which youth see word-sentence pairs personalized to their anxiety symptoms, and indicate whether these are related. Youth receive feedback aimed to reduce interpretation bias.	Interpretation Control Condition (ICC) n=25 Participants 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. Interpretation Control Condition (ICC): Computerized control condition in which youth see word-sentence pairs personalized to their anxiety symptoms. Youth indicate whether these are related, but are not provided with feedback that aims to "train" a reduction in interpretation bias.
Change in Self-reported Interpretation Bias as Measured by the Children's Automatic Thoughts Scale (CATS)	6.52 score on a scale Standard Deviation 10.22	19.00 score on a scale Standard Deviation 16.47

SECONDARY outcome

Timeframe: 6 weeks; post-intervention time point

Population: The average number of 16 possible CBM-I/ICC trainings completed per group. Note that this number averages (i.e., Mean score) across all participants in the randomized group. Two participants (siblings) dropped from CBM-I following the second training session due to an unrelated medical emergency and hospitalization, and one participant was removed from the ICC group following randomization and before completion of any trainings due to participant not being eligible for study participation.

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.

Outcome measures

Outcome measures
Measure	Cognitive Bias Modification for Interpretations (CBM-I) n=23 Participants 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. Cognitive Bias Modification for Interpretations (CBM-I): Computerized intervention in which youth see word-sentence pairs personalized to their anxiety symptoms, and indicate whether these are related. Youth receive feedback aimed to reduce interpretation bias.	Interpretation Control Condition (ICC) n=24 Participants 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. Interpretation Control Condition (ICC): Computerized control condition in which youth see word-sentence pairs personalized to their anxiety symptoms. Youth indicate whether these are related, but are not provided with feedback that aims to "train" a reduction in interpretation bias.
Number of Trainings Completed of 16 Intended Sessions	16 number of 16 trainings completed Standard Deviation 0	15.83 number of 16 trainings completed Standard Deviation 0.82

SECONDARY outcome

Timeframe: 6 weeks

Population: The PAQ is scored on a scale from 0 to 50, with higher scores indicating higher acceptability. Scores of 30-39 indicate moderate acceptability and scores of 40-50 indicate high acceptability.

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.

Outcome measures

Outcome measures
Measure	Cognitive Bias Modification for Interpretations (CBM-I) n=23 Participants 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. Cognitive Bias Modification for Interpretations (CBM-I): Computerized intervention in which youth see word-sentence pairs personalized to their anxiety symptoms, and indicate whether these are related. Youth receive feedback aimed to reduce interpretation bias.	Interpretation Control Condition (ICC) n=24 Participants 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. Interpretation Control Condition (ICC): Computerized control condition in which youth see word-sentence pairs personalized to their anxiety symptoms. Youth indicate whether these are related, but are not provided with feedback that aims to "train" a reduction in interpretation bias.
Participant/Parent Acceptability Questionnaire (PAQ) Parent PAQ	47.25 score on a scale Standard Deviation 5.17	42.91 score on a scale Standard Deviation 4.03
Participant/Parent Acceptability Questionnaire (PAQ) Youth PAQ	38.61 score on a scale Standard Deviation 8.03	33.87 score on a scale Standard Deviation 8.41

Adverse Events

Cognitive Bias Modification for Interpretations (CBM-I)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Interpretation Control Condition (ICC)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Cognitive Bias Modification for Interpretations (CBM-I) n=25 participants at risk 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. Cognitive Bias Modification for Interpretations (CBM-I): Computerized intervention in which youth see word-sentence pairs personalized to their anxiety symptoms, and indicate whether these are related. Youth receive feedback aimed to reduce interpretation bias.	Interpretation Control Condition (ICC) n=25 participants at risk 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. Interpretation Control Condition (ICC): Computerized control condition in which youth see word-sentence pairs personalized to their anxiety symptoms. Youth indicate whether these are related, but are not provided with feedback that aims to "train" a reduction in interpretation bias.
General disorders COVID, cold, flu, other illness	20.0% 5/25 • Number of events 25 • Adverse event data were collected from study visit 2 (post-randomization and post-eligibility determination at Visit 1), and weekly through week 6 of study participation. Adverse events were queried at each study visit starting study visit 2 after participants were enrolled. The independent evaluator queried youth and caregiver separately about potential adverse events using a table provided by the NIMH CREST program. Nearly all adverse events were either COVID related (e.g., participant was exposed to or had COVID transmission from their daily life activities) or cold/flu related.	16.0% 4/25 • Number of events 25 • Adverse event data were collected from study visit 2 (post-randomization and post-eligibility determination at Visit 1), and weekly through week 6 of study participation. Adverse events were queried at each study visit starting study visit 2 after participants were enrolled. The independent evaluator queried youth and caregiver separately about potential adverse events using a table provided by the NIMH CREST program. Nearly all adverse events were either COVID related (e.g., participant was exposed to or had COVID transmission from their daily life activities) or cold/flu related.

Additional Information

Michelle Rozenman, Ph.D., Director, BRAVE Lab & Associate Professor, Department of Psychology

University of Denver

Phone: 303-871-6448

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place