Exercise priming to enhance therapeutic bond and behavioral activation in CBT for MDD: a randomized controlled target-engagement trial with remission signal

Jacob D. Meyer; Shania J.E. Kelly; John M. Gidley; Jeni E. Lansing; Seana L. Smith; Sydney L. Churchill; Madeleine L. Connolly; Emily B.K. Thomas; Simon B. Goldberg; Heather C. Abercrombie; Thomas A. Murray; Nathaniel G. Wade

doi:10.1016/j.jad.2026.121606

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Exercise priming to enhance therapeutic bond and behavioral activation in CBT for MDD: a randomized controlled target-engagement trial with remission signal

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Exercise priming to enhance therapeutic bond and behavioral activation in CBT for MDD: a randomized controlled target-engagement trial with remission signal

Jacob D. Meyer, Shania J.E. Kelly, John M. Gidley, Jeni E. Lansing, Seana L. Smith, Sydney L. Churchill, Madeleine L. Connolly, Emily B.K. Thomas, Simon B. Goldberg, Heather C. Abercrombie, …

Journal of affective disorders, Vol.405, 121606

03/13/2026

DOI: 10.1016/j.jad.2026.121606

PMCID: PMC13064449

PMID: 41833616

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Abstract

Major depressive disorder (MDD) is a debilitating condition with frequent relapses. Augmentation strategies may improve psychotherapy outcomes, particularly if they enhance mechanisms of change. Using an experimental therapeutics approach, this pilot trial evaluated whether 30 min of individual moderate exercise immediately before individual cognitive behavioral therapy (ActiveCBT) engages two mechanistic targets (behavioral activation and therapeutic alliance) compared to a time- and attention-matched control (CalmCBT). Forty adults with DSM-5 MDD were severity-stratified and randomized to 8 weeks of ActiveCBT (n = 19) or CalmCBT (n = 21). Primary outcomes were the Working Alliance Inventory–Short Revised (WAI; Bond, Task, Goals subscales) and Behavioral Activation for Depression Scale (BADS). Depression outcomes included Hamilton Rating Scale for Depression (HAMD) response (≥50% reduction) and remission (HAMD<8) from a masked assessor. Generalized estimating equations estimated group effects across time, standardized as Cohen's d, with a priori success defined as d ≥ 0.35 for both or d ≥ 0.55 for either WAI or BADS. The average standardized effect for WAI-Bond favoring ActiveCBT was d = 0.36 (95% CI: −0.19, 0.90, p = 0.20) and BADS was d = 0.43 (−0.07, 0.94; p = 0.09). Secondary exploratory analyses found a significant remission benefit for ActiveCBT over CalmCBT (69% vs 33%, p < 0.05), with similar response rates. Exercise priming demonstrated directional mechanistic signals in both specific (behavioral activation) and nonspecific (therapeutic bond) targets, with potential remission benefits from exploratory analyses. These findings preliminarily suggest that exercising before therapy could augment CBT and offer a safe, accessible way to potentially boost its antidepressant effects. This study was prospectively registered at ClinicalTrials.gov (NCT06001346). •We report a pilot/target engagement trial of exercise vs calm priming of CBT in MDD•Exercising right before therapy enhanced working alliance and behavioral activation•Directional effects met pre-specified thresholds for both alliance and activation•A large remission benefit was found for ActiveCBT in exploratory analyses•Effective group blinding in treatment and assessments led to high internal validity

Exercise

Depression treatment

Therapy augmentation

Treatment innovation

Treatment mechanisms

Details

Title: Subtitle: Exercise priming to enhance therapeutic bond and behavioral activation in CBT for MDD: a randomized controlled target-engagement trial with remission signal
Creators: Jacob D. Meyer - University of Wisconsin–Madison
Shania J.E. Kelly - University of Wisconsin–Madison
John M. Gidley - University of Wisconsin–Madison
Jeni E. Lansing - University of Wisconsin–Madison
Seana L. Smith - University of Wisconsin–Madison
Sydney L. Churchill - Iowa State University
Madeleine L. Connolly - University of Wisconsin–Madison
Emily B.K. Thomas - University of Iowa
Simon B. Goldberg - University of Wisconsin–Madison
Heather C. Abercrombie - University of Wisconsin–Madison
Thomas A. Murray - University of Minnesota
Nathaniel G. Wade - Iowa State University
Resource Type: Journal article
Publication Details: Journal of affective disorders, Vol.405, 121606
DOI: 10.1016/j.jad.2026.121606
PMID: 41833616
PMCID: PMC13064449
NLM abbreviation: J Affect Disord
ISSN: 0165-0327
eISSN: 1573-2517
Publisher: Elsevier B.V
Grant note: NIMH: R61MH129407 National Center for Complementary and Integrative Health
This work was supported by the NIMH (R61MH129407) awarded to Dr. Meyer. Drs. Meyer and Wade were also supported by R01MH130566. Dr. Goldberg was supported via a career development award from the National Center for Complementary and Integrative Health (K23AT010879) . The NIH had no role in the study design, collection, analysis and interpretation of data, writing of the report or decision to submit the article for publication.
Language: English
Date published: 03/13/2026
Academic Unit: Psychological and Brain Sciences
Record Identifier: 9985147209202771

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