# Multi-level Mechanisms of Behavioral Activation Therapy for Adolescent Depression

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $782,204

## Abstract

Project Summary/Abstract
Major Depressive Disorder (MDD) is a devastating clinical disorder and the leading cause of disability
worldwide. Adolescence is a key developmental period during which risk for the development of depression is
greatest. Behavioral Activation (BA) psychotherapy has emerged as a first-line treatment for adolescent
depression, yet the underlying neurobiological mechanisms that mediate treatment efficacy remain unclear.
Understanding these target mechanisms is fundamental to developing novel adaptations of BA, augmenting
other treatments with BA, and designing new interventions informed by greater comprehension of neural target
mechanisms. In the current application, we seek to identify the neural mechanisms that mediate treatment
response during BA therapy for adolescent depression. Critically, reductions in avoidance behavior and
successful BA treatment may occur through manipulation of multiple neural targets operating on different
timescales between and/or within individuals. In cross-sectional neuroimaging studies of adolescent
depression, the most common markers are hypo-responding to reward cues in the ventral striatum (VS) and
ventromedial prefrontal cortex (vmPFC) and hyper-responding to negative information in the amygdala and the
salience network–comprising the anterior insula (aI) and dorsal anterior cingulate (dACC). These patterns of
hypo- and hyper-responding regions may independently or jointly contribute to behavioral avoidance by the
RDoC concepts of reduced motivation for rewards and threat avoidance, respectively. Consequently, a fuller
understanding of target engagement for BA requires multiple assessments linking trajectories of behavioral
and symptom change with trajectories of change in these neural circuits over the course of therapy as opposed
to just pre/post comparisons. To address these concerns, we propose to acquire ecological momentary
assessment (EMA) and longitudinal neuroimaging data in a sample of 96 depressed adolescents while they
complete a 16-week course of BA therapy. Three task-based fMRI scans will occur at baseline and after
sessions 7 and 16, and will include a set of paradigms focused on assessing behavioral avoidance for
monetary and social rewards. In addition, two brief “behavioral-scheduling-in-scanner” sessions will occur at
sessions 3 and 9 during which the patient and therapist will engage in a component of BA therapy while the
patient undergoes an fMRI scan. This “behavioral-secheduling-in-scanner” protocol will allow us to better
determine the ecological validity of task-based measures of target engagement during psychotherapy. Taken
together, these data will enable understanding of the neural mechanisms through which BA reduces avoidance
behavior and thereby treats depression, Further, these data will establish a platform for developing future
modifications of BA techniques and/or novel treatments based on identifiable neural targets.

## Key facts

- **NIH application ID:** 10453989
- **Project number:** 1R01MH126985-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** W. EDWARD CRAIGHEAD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $782,204
- **Award type:** 1
- **Project period:** 2022-05-03 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10453989

## Citation

> US National Institutes of Health, RePORTER application 10453989, Multi-level Mechanisms of Behavioral Activation Therapy for Adolescent Depression (1R01MH126985-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10453989. Licensed CC0.

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