Gamified Attention Bias Modification Training to Augment Cognitive–Behavioral Therapy for Youth Anxiety Disorders: A Randomized Controlled Trial - 26/09/25

Doi : 10.1016/j.jaac.2025.08.010

Meghan E. Byrne, PhD ^a,^⁎ , Simone P. Haller, PhD ^a, Julia O. Linke, PhD ^b, Krystal M. Lewis, PhD ^a, Erin D. Berman, PhD ^a, Lauren M. Henry, PhD ^a, David Pagliaccio, PhD ^c, David Quezada, BA ^d, Marisa Meyer, MA ^e, Rany Abend, PhD ^f, Katharina Kircanski, PhD ^a, Wendy K. Silverman, PhD ^g, Amit Lazarov, PhD ^h, Yair Bar-Haim, PhD ^h, Melissa A. Brotman, PhD ^a, Daniel S. Pine, MD ^a
^a National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
^b University of Freiburg, Freiburg im Breisgau, Germany
^c New York State Psychiatric Institute, New York, New York
^d University of California, San Francisco School of Medicine, San Francisco, California
^e Temple University, Philadelphia, Pennsylvania
^f Reichman University, Herzliya, Israel
^g Yale University School of Medicine, New Haven, Connecticut
^h Tel Aviv University, Tel Aviv, Israel

^∗Correspondence to Meghan E. Byrne, PhD, 9000 Rockville Pike, Bldg 15K, MSC-2670, Bethesda, MD 208929000 Rockville PikeBldg 15KMSC-2670BethesdaMD20892

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Friday 26 September 2025

Abstract

Objective

Augmenting cognitive–behavioral therapy (CBT) with attention bias modification training (ABMT) may maximize therapeutic benefit for anxiety through targeting different underlying processes. Yet, corresponding neural mechanisms are unclear. This preregistered double-blind, randomized controlled trial assigned youth with anxiety disorders receiving CBT to active or sham gamified ABMT. Group differences in clinical efficacy, and associations between amygdala connectivity and treatment outcomes, were examined.

Method

Pediatric patients (N = 121; 8-17 years of age) with anxiety disorders were randomized to active or sham gamified ABMT alongside 12 weeks of manualized CBT. Primary outcomes were clinician-rated Pediatric Anxiety Rating Scale (PARS) and Clinical Global Impression—Improvement (CGI-I) Scale scores. Amygdala seed-based connectivity during a functional magnetic resonance imaging (fMRI) dot-probe attention bias task was measured before and after treatment in patients, and across the same time interval in healthy controls.

Results

Over treatment, PARS decreased significantly in both groups (F_2,214 = 82.84; p < .001, η_p² = 0.44). Contrary to hypotheses, active ABMT did not enhance symptom reductions (F_2,214 = 0.61; p=.54, η_p² < 0.01). There was no difference in the proportion of CGI-I treatment responders vs nonresponders between active and sham (χ² = 0.76, p = .38) treatments. Amygdala connectivity is reported, but should be interpreted with caution because of poor observed test–retest reliability in healthy controls (intraclass correlation coefficient [3,1] < 0.4). Lower posttreatment anxiety was associated with weaker left amygdala connectivity with several cortical regions on threat-congruent trials.

Conclusion

Hypotheses that youth receiving active gamified ABMT+CBT would show greater improvement were not supported. Findings highlight the need to explore alternative attention bias modification strategies for augmenting the clinical response to CBT for anxiety. Future research should continue to examine reliability of attention bias tasks adapted for fMRI.

Clinical Trial Registration Information

A Clinical Trial of a Gamified Attention Bias Modification Training in Anxious Youth; NCT03283930.

Study Registration Information

The Nature of the Effect; fxc54github

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Key words : RCT, attention bias modification, fMRI, cognitive-behavioral therapy, anxiety disorders

Plan

Efficacy of ABMT: Primary Clinical Outcomes

Reliability of Amygdala–Seed Connectivity

Pretreatment Baseline Connectivity and Behavioral Differences

Associations With Treatment Response

Discussion

Clinical and Behavioral Differences

Amygdala Connectivity

CRediT authorship contribution statement

	This article was reviewed under and accepted by Ad Hoc Editor Paul E. Croarkin, DO, MSCS
	The authors have reported funding for this work by the NIMH Intramural Research Program project ZIAMH002781 (principal investigator, Dr. Daniel S. Pine); this project was conducted under Clinical Study Protocol 01-M-0192A (ClinicalTrials.gov identifiers: NCT00018057 and NCT03283930).
	This study was presented at the American College of Neuropsychopharmacology; December 8-11, 2024; Phoenix, Arizona.
	Data Sharing: In accordance with the NIH Data Management and Sharing Policy, participants’ individual data will be shared in a repository for those participants that consented to share their data publicly. Given not all participants consented to share their data, exact replication of analyses with the open dataset will not be possible. Data will be available immediately following publication and there will be no end date. Additionally, all code used for analyses for this data will be shared on GitHub.
	Simone P. Haller, PhD, served as the statistical expert for this research.
	The authors thank the children and families who participated in the study. This work utilized the computational resources of the NIH HPC Biowulf cluster (hpc.nih.gov/).
	Disclosure: Meghan E. Byrne, Simone P. Haller, Julia O. Linke, Krystal M. Lewis, Erin Berman, Lauren M. Henry, David Pagliaccio, David Quezada, Marisa Meyer, Rany Abend, Katharina Kircanski, Wendy K. Silverman, Amit Lazarov, Yair Bar-Haim, Melissa A. Brotman, and Daniel S. Pine have reported no biomedical financial interests or potential conflicts of interest. This research was supported by the Intramural Research Program of the National Institutes of Health (NIH). The contributions of the NIH authors were made as part of their official duties as NIH federal employees, are in compliance with agency policy requirements, and are considered Works of the United States Government. However, the findings and conclusions presented in this paper are those of the authors and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services.