Prediction of generalized anxiety disorder treatment outcomes with neurobehavioral responses to approach-avoidance conflict: a randomized clinical trial

Abstract Treatments for generalized anxiety disorder (GAD) often aim to address maladaptive approach-avoidance behavior patterns. Approach-avoidance conflict (AAC) offers a potential framework for identifying treatment outcome predictors and informing optimization of GAD treatment. The current study...

Full description

Saved in:
Bibliographic Details
Main Authors: Hannah Berg, Timothy J. McDermott, Rayus Kuplicki, Hung-Wen Yeh, Wesley K. Thompson, Ryan Smith, Elisabeth Akeman, Namik Kirlic, Ashley Clausen, Mallory Cannon, Evan White, Christopher R. Martell, Kate B. Wolitzky-Taylor, Michelle G. Craske, James L. Abelson, Martin P. Paulus, Robin L. Aupperle
Format: Article
Language:English
Published: Nature Publishing Group 2025-07-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-025-03460-x
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849238370474000384
author Hannah Berg
Timothy J. McDermott
Rayus Kuplicki
Hung-Wen Yeh
Wesley K. Thompson
Ryan Smith
Elisabeth Akeman
Namik Kirlic
Ashley Clausen
Mallory Cannon
Evan White
Christopher R. Martell
Kate B. Wolitzky-Taylor
Michelle G. Craske
James L. Abelson
Martin P. Paulus
Robin L. Aupperle
author_facet Hannah Berg
Timothy J. McDermott
Rayus Kuplicki
Hung-Wen Yeh
Wesley K. Thompson
Ryan Smith
Elisabeth Akeman
Namik Kirlic
Ashley Clausen
Mallory Cannon
Evan White
Christopher R. Martell
Kate B. Wolitzky-Taylor
Michelle G. Craske
James L. Abelson
Martin P. Paulus
Robin L. Aupperle
author_sort Hannah Berg
collection DOAJ
description Abstract Treatments for generalized anxiety disorder (GAD) often aim to address maladaptive approach-avoidance behavior patterns. Approach-avoidance conflict (AAC) offers a potential framework for identifying treatment outcome predictors and informing optimization of GAD treatment. The current study examined whether pre-treatment neurobehavioral AAC indices predict symptom improvement in behavioral activation (BA) and exposure therapy (EXP) for GAD. Treatment-seeking adults meeting criteria for GAD completed a randomized clinical trial with pre-treatment blinding, conducted from 2016–2021. Participants were randomized to complete 10 manualized sessions of BA or EXP. Participants completed an AAC task during functional magnetic resonance imaging pre-treatment. Computational parameters of task behavior were derived, and neural activity was assessed during decision-making and positive and negative outcomes of decisions. Outcome measures were GAD symptoms and depressive symptoms. Of 121 participants recruited, 56 (29 BA, 27 EXP; mean age 33.0 years; 12.5% male) treatment completers were included in analyses. Greater AAC task avoidance (d = −0.28) and greater left dorsolateral prefrontal cortex activation during negative outcomes (d = −0.32), predicted greater symptom reduction across treatments. Blunted left amygdala activation to positive outcomes was associated at a trend level with favorable symptom reduction for BA but not EXP (d = −0.20). The dorsolateral prefrontal cortex may be a target for enhancing behavior therapy outcomes generally, while left amygdala activation to positive affect may be a target for enhancing outcomes for BA. These findings may inform the optimization of behavioral therapies for GAD and hold potential for transdiagnostic applications, warranting larger, longitudinal studies in clinical settings. Clinical Trials Registration: ClinicalTrials.gov NCT02807480.
format Article
id doaj-art-7dbb2851d7a841758aadbcf70708ccaf
institution Kabale University
issn 2158-3188
language English
publishDate 2025-07-01
publisher Nature Publishing Group
record_format Article
series Translational Psychiatry
spelling doaj-art-7dbb2851d7a841758aadbcf70708ccaf2025-08-20T04:01:40ZengNature Publishing GroupTranslational Psychiatry2158-31882025-07-0115111110.1038/s41398-025-03460-xPrediction of generalized anxiety disorder treatment outcomes with neurobehavioral responses to approach-avoidance conflict: a randomized clinical trialHannah Berg0Timothy J. McDermott1Rayus Kuplicki2Hung-Wen Yeh3Wesley K. Thompson4Ryan Smith5Elisabeth Akeman6Namik Kirlic7Ashley Clausen8Mallory Cannon9Evan White10Christopher R. Martell11Kate B. Wolitzky-Taylor12Michelle G. Craske13James L. Abelson14Martin P. Paulus15Robin L. Aupperle16Laureate Institute for Brain ResearchLaureate Institute for Brain ResearchLaureate Institute for Brain ResearchHealth Services & Outcomes Research, Children’s Mercy HospitalLaureate Institute for Brain ResearchLaureate Institute for Brain ResearchLaureate Institute for Brain ResearchLaureate Institute for Brain ResearchSaint Luke’s Marion Bloch Neuroscience InstituteLaureate Institute for Brain ResearchLaureate Institute for Brain ResearchDepartment of Psychological and Brain Sciences, University of Massachusetts–AmherstPsychology, Psychiatry and Biobehavioral Sciences, University of CaliforniaPsychology, Psychiatry and Biobehavioral Sciences, University of CaliforniaDepartment of Psychiatry, University of MichiganLaureate Institute for Brain ResearchLaureate Institute for Brain ResearchAbstract Treatments for generalized anxiety disorder (GAD) often aim to address maladaptive approach-avoidance behavior patterns. Approach-avoidance conflict (AAC) offers a potential framework for identifying treatment outcome predictors and informing optimization of GAD treatment. The current study examined whether pre-treatment neurobehavioral AAC indices predict symptom improvement in behavioral activation (BA) and exposure therapy (EXP) for GAD. Treatment-seeking adults meeting criteria for GAD completed a randomized clinical trial with pre-treatment blinding, conducted from 2016–2021. Participants were randomized to complete 10 manualized sessions of BA or EXP. Participants completed an AAC task during functional magnetic resonance imaging pre-treatment. Computational parameters of task behavior were derived, and neural activity was assessed during decision-making and positive and negative outcomes of decisions. Outcome measures were GAD symptoms and depressive symptoms. Of 121 participants recruited, 56 (29 BA, 27 EXP; mean age 33.0 years; 12.5% male) treatment completers were included in analyses. Greater AAC task avoidance (d = −0.28) and greater left dorsolateral prefrontal cortex activation during negative outcomes (d = −0.32), predicted greater symptom reduction across treatments. Blunted left amygdala activation to positive outcomes was associated at a trend level with favorable symptom reduction for BA but not EXP (d = −0.20). The dorsolateral prefrontal cortex may be a target for enhancing behavior therapy outcomes generally, while left amygdala activation to positive affect may be a target for enhancing outcomes for BA. These findings may inform the optimization of behavioral therapies for GAD and hold potential for transdiagnostic applications, warranting larger, longitudinal studies in clinical settings. Clinical Trials Registration: ClinicalTrials.gov NCT02807480.https://doi.org/10.1038/s41398-025-03460-x
spellingShingle Hannah Berg
Timothy J. McDermott
Rayus Kuplicki
Hung-Wen Yeh
Wesley K. Thompson
Ryan Smith
Elisabeth Akeman
Namik Kirlic
Ashley Clausen
Mallory Cannon
Evan White
Christopher R. Martell
Kate B. Wolitzky-Taylor
Michelle G. Craske
James L. Abelson
Martin P. Paulus
Robin L. Aupperle
Prediction of generalized anxiety disorder treatment outcomes with neurobehavioral responses to approach-avoidance conflict: a randomized clinical trial
Translational Psychiatry
title Prediction of generalized anxiety disorder treatment outcomes with neurobehavioral responses to approach-avoidance conflict: a randomized clinical trial
title_full Prediction of generalized anxiety disorder treatment outcomes with neurobehavioral responses to approach-avoidance conflict: a randomized clinical trial
title_fullStr Prediction of generalized anxiety disorder treatment outcomes with neurobehavioral responses to approach-avoidance conflict: a randomized clinical trial
title_full_unstemmed Prediction of generalized anxiety disorder treatment outcomes with neurobehavioral responses to approach-avoidance conflict: a randomized clinical trial
title_short Prediction of generalized anxiety disorder treatment outcomes with neurobehavioral responses to approach-avoidance conflict: a randomized clinical trial
title_sort prediction of generalized anxiety disorder treatment outcomes with neurobehavioral responses to approach avoidance conflict a randomized clinical trial
url https://doi.org/10.1038/s41398-025-03460-x
work_keys_str_mv AT hannahberg predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT timothyjmcdermott predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT rayuskuplicki predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT hungwenyeh predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT wesleykthompson predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT ryansmith predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT elisabethakeman predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT namikkirlic predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT ashleyclausen predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT mallorycannon predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT evanwhite predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT christopherrmartell predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT katebwolitzkytaylor predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT michellegcraske predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT jameslabelson predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT martinppaulus predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial
AT robinlaupperle predictionofgeneralizedanxietydisordertreatmentoutcomeswithneurobehavioralresponsestoapproachavoidanceconflictarandomizedclinicaltrial