This research was supported by the Intramural Research Program of the National Institute of Mental Health (NIMH), National Institutes of Health (NIH; ZIAMH002778-17 and ZIAMH002786-15) and was conducted under NIH Clinical Study Protocols 15-M-0182 and 02-M-0021 (ClinicalTrials.gov ID: NCT02531893 and NCT00025935). J.S. was supported by a grant from NIH, NIMH, (K23MH113731) and the Pediatric Mental Health Institute at Children’s Hospital Colorado and the Division of Child and Adolescent Psychiatry, Department of Psychiatry, University of Colorado School of Medicine. The funding source was not involved in study design; the collection, analysis, and interpretation of data; writing of the report; and the decision to submit the article for publication. M.M. and I.P.-V. are supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at University Hospitals Bristol National Health Service (NHS) Foundation Trust and the University of Bristol. The views expressed in this publication are those of the author(s) and not necessarily those of NHS, NIHR, or the Department of Health and Social Care.

Author Contributions

Conceptualization: Stoddard, Penton-Voak, Bar-Haim, Munafò, Towbin, Brotman

Data curation: Haller, Stoddard, Botz-Zapp, Clayton, MacGillivray, Perhamus, Stiles

Formal analysis: Haller, Stoddard, Brotman

Funding acquisition: Brotman

Investigation: Kircanski, Bar-Haim

Methodology: Brotman

Project administration: Haller, Botz-Zapp, Clayton, MacGillivray, Perhamus, Stiles, Kircanski, Towbin, Brotman

Resources: Kircanski, Towbin

Software: Haller, Stoddard, Penton-Voak, Munafò

Supervision: Kircanski, Bar-Haim, Munafò, Towbin, Brotman

Validation: Haller

Visualization: Haller

Writing – original draft: Haller

Writing – review and editing: Stoddard, Botz-Zapp, Clayton, MacGillivray, Perhamus, Stiles, Kircanski, Penton-Voak, Bar-Haim, Munafò, Towbin, Brotman

The authors thank the clinicians, patients, and their families that contributed to this research.

Disclosure: Dr. Haller has received grant support through a Brain and Behavior Research Foundation (BBRF) Young Investigator Award. Dr. Stoddard has received grant or research support from NIMH. He has served as a DSMB committee member: Threat Interpretation Bias as Cognitive Marker and Treatment Target in Pediatric Anxiety (R61 Phase). Drs. Penton-Voak and Munafò are co-directors of Jericoe Ltd., a company that licenses software for the assessment and modification of emotion recognition. Dr. Bar-Haim has received grant or research support from the Israel Science Foundation and the US Department of Defense. Dr. Brotman has served as a principal investigator (PI) on a Bench-to-Bedside grant from NIH. Drs. Kircanski and Towbin, Mr. Botz-Zapp, and Mss. Clayton, MacGillivray, Perhamus, and Stiles have reported no biomedical financial interests or potential conflicts of interest.

Clinical trial registration information: Psychological Treatments for Youth With Severe Irritability; https://clinicaltrials.gov/; NCT02531893.