Examining Reward-Related Predictors and Mechanisms of Change in BA Treatment for Anhedonic Adolescents

NCT02498925 | Completed Results DMC

• 2 other identifiers: 2015-D000149K23MH108752
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The prevalence of major depressive disorder (MDD) is relatively low in childhood (i.e., 1-3%), but increases substantially during adolescence. By the age of 18, approximately 15% of adolescents will have experienced at least one episode of MDD. A growing body of research implicates abnormalities in reward circuitry as playing a critical role in the development and maintenance of depressive symptoms in adolescents. Importantly, these reward-circuitry abnormalities have been linked to anhedonia (i.e., decreased pleasure or blunted reactivity to rewarding stimuli). Behavioral Activation (BA) represents a promising - and relatively simple to deliver - nonpharmacologic intervention for adolescent depression, which has been shown to be at least as effective as Cognitive Behavioral Therapy (CBT) with regards to symptom reduction and lowering the risk of relapse in adult samples. More recently, promising data have emerged from the application of BA to depressed adolescents. BA can be conceptualized as a treatment directly targeting anhedonia. More specifically, BA targets anhedonia through behavioral change strategies aimed at gradually increasing patients' exposure to and engagement with rewarding stimuli and positively reinforcing experiences. Given this treatment focus, BA may be particularly beneficial for adolescents struggling with relatively elevated levels of anhedonic symptoms. Accordingly, the present study will examine the role of anhedonia and reward functioning in predicting treatment response in BA. In addition, analyses will be conducted examining the reward-related neural and behavioral mechanisms underlying anhedonic symptom improvement in BA.

Conditions

Anhedonia

Outcome Measures

Primary Outcomes (3)

• Change in Anhedonic (Snaith-Hamilton Pleasure Scale; SHAPS) Symptoms

  Snaith-Hamilton Pleasure Scale (SHAPS) is a 14-item questionnaire that measures the capacity to experience pleasure (lack of pleasure is referred to as anhedonia). Total scores range from 14-56 with higher scores reflecting more anhedonia

  Change from pre-treatment (baseline) to post-treatment (12 weeks)

• Change in Brain (Striatal and Medial PFC) Activation During a Monetary Reward Gambling Task

  During the pre- and post-treatment fMRI scan, youth completed an event-related card- guessing task designed to assess brain responses to the anticipation and receipt of monetary reward and loss. The task included four 6.5-min blocks in which youth guessed whether the value of a card was higher or lower than 5. Based on the trial type (win, loss, neutral), youth won or lost money (win trials +$1.00, loss trails -$0.50, total earnings $16.00). We focused on neural response to win or loss (contrasted with neutral) outcomes. Individual contrast images were used to create second-level random effects models using one-sample t-tests for the win \> neutral and loss \> neutral contrasts. Mean beta weights for the medial PFC (mPFC) and striatal (NAcc, caudate, and putamen) regions of interest (ROIs) were extracted for each contrast. For details and results for each brain regions see Neuropsychopharmacology (2023) 48:623-632; https://doi.org/10.1038/s41386-022-01481-4

  Change from pre-treatment (baseline) to post-treatment (12 weeks). Positive values reflect increases in neural response

• Change in Performance (Reward Learning) on the Probabilistic Reward Task (PRT) Computer Task

  Each PRT trial begins with a fixation cross (500 ms) followed by a cartoon face without either a mouth or a nose (counterbalanced across subjects and session). After a 500 ms delay, a short or long mouth/nose was presented (100 ms). Participants then indicated whether they saw a short or long mouth or nose. For each block, 40 trials with correct responses resulted in a monetary reward of $0.20. In these cases, participants were presented with a screen that said "Correct! You won 20 cents." While long and short mouths or noses were presented with equal frequency across the block, one length received a reward for correct identification 3x more frequently (i.e., rich stimulus; n=30) than the other (i.e., lean stimulus; n=10). Response bias favoring the rich stimulus was calculated using an established formula (see reference below for details). "Reward Learning" was calculated as the change in response bias score from block 1 to block 2. Higher scores reflect greater reward learning

  Change in reward learning from pre-treatment (baseline) to post-treatment (12 weeks).

Study Arms (2)

Anhedonic teens receiving Behavioral Activation (BA)

EXPERIMENTAL

12 weeks (1 50-min session per week) of Behavioral Activation for the anhedonic adolescents. Behavioral Activation is a psychosocial treatment for depression focused on gradually re-engaging patients with sources of reinforcement and reward in their environment (e.g., increasing activites and interpersonal interactions). In contrast to Cognitive Behavioral Therapy, and as the name implies, Behavioral Activation focuses on behavioral strategies to improve mood and places little emphasis on cognitive restructuring techniques.

Behavioral: Behavioral Activation

Non-anhedonic teens (not receiving BA)

NO INTERVENTION

A group of adolescents with no anhedonia were recruited

Interventions

Behavioral Activation BEHAVIORAL

Behavioral Activation is a psychosocial treatment for depression focused on gradually re-engaging patients with sources of reinforcement and reward in their environment (e.g., increasing activites and interpersonal interactions). In contrast to Cognitive Behavioral Therapy, and as the name implies, Behavioral Activation focuses on behavioral change strategies to improve mood and places little emphasis on cognitive restructuring techniques.

Anhedonic teens receiving Behavioral Activation (BA)

Eligibility Criteria

• Age: 13 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Both genders, any ethnicity
• Ages 13-18
• English as first language or English fluency
• Right handed
• Smartphone with iOS or Android platform (for EMA)
• Anhedonic Sample: Total Snaith Hamilton Pleasure Scale (SHAPS) score ≥ 3; Healthy Control Sample: Total SHAPS score = 0

You may not qualify if:

• History of head trauma with loss of consciousness
• History of seizure disorder
• Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
• History of cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine)
• History of use of dopaminergic drugs (including methylphenidate)
• Clinical or laboratory evidence of hypothyroidism
• Systemic medical or neurological illness that could impact fMRI measures of cerebral blood flow
• Positive urine pregnancy test
• A. Anhedonic Adolescents:
• Subjects with suicidal ideation where outpatient BA treatment is determined unsafe or inappropriate by the study clinician. These patients will be immediately referred to appropriate clinical treatment
• History or current diagnosis of any of the following DSM-5 psychiatric illnesses: schizophrenia spectrum or other psychotic disorder, bipolar disorder, OCD, PTSD, substance (including alcohol) use disorder within the past 12 months or lifetime severe substance use disorder (i.e., meeting former DSM-IV criteria for past substance dependence). Simple phobia, social anxiety disorder, panic disorder, and generalized anxiety disorder will be allowed only if secondary to anhedonia
• Meet criteria for chronic depression (current episode \> 2 years)
• Currently receiving psychotropic treatment or psychotherapy
• Absence of any psychotropic medications: 8 weeks for fluoxetine, 4 weeks for neuroleptics, 8 weeks for benzodiazepines, 6 weeks any other antidepressants
• B. Healthy Control Adolescents:

Sponsors & Collaborators

• Mclean Hospital: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

Related Publications (4)

• Webb CA, Murray L, Tierney AO, Forbes EE, Pizzagalli DA. Reward-related predictors of symptom change in behavioral activation therapy for anhedonic adolescents: a multimodal approach. Neuropsychopharmacology. 2023 Mar;48(4):623-632. doi: 10.1038/s41386-022-01481-4. Epub 2022 Oct 28.

  PMID: 36307561 RESULT

• Webb CA, Murray L, Tierney AO, Gates KM. Dynamic processes in behavioral activation therapy for anhedonic adolescents: Modeling common and patient-specific relations. J Consult Clin Psychol. 2024 Aug;92(8):454-465. doi: 10.1037/ccp0000830. Epub 2023 Jun 5.

  PMID: 37276084 RESULT

• Ren B, Balkind EG, Pastro B, Israel ES, Pizzagalli DA, Rahimi-Eichi H, Baker JT, Webb CA. Predicting states of elevated negative affect in adolescents from smartphone sensors: a novel personalized machine learning approach. Psychol Med. 2023 Aug;53(11):5146-5154. doi: 10.1017/S0033291722002161. Epub 2022 Jul 27.

  PMID: 35894246 RESULT

• Fisher H, Jaffe NM, Rahimi-Eichi H, Forbes EE, Pizzagalli DA, Baker JT, Webb CA. Measuring activation during behavioral activation therapy: a proof-of-concept study using smartphone sensors and LLM-derived ratings in adolescents with anhedonia. NPP Digit Psychiatry Neurosci. 2025 Oct 13;3:24. doi: 10.1038/s44277-025-00045-w. eCollection 2025.

  PMID: 41098338 DERIVED

MeSH Terms

Conditions

Anhedonia

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

* Small sample size * Non-anhedonic adolescents who completed neural and behavioral assessments at timepoints corresponding to the anhedonic group controlled for the effect of repeated assessments and task practice effects. But, a future study with an active control condition is needed to test the specificity of findings to BA vs. other interventions for the treatment of anhedonia in youth * Generalizability was limited since our sample was largely White and non-Hispanic females

Results Point of Contact

• Title: Christian Webb, PhD
• Organization: McLean Hospital

cwebb@mclean.harvard.edu

6178554429

Study Officials

• Christian A Webb, Ph.D.

  McLean Hospital & McLean Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Harvard Medical School; Associate Psychologist, McLean Hospital

Study Record Dates

• First Submitted: July 10, 2015
• First Posted: July 15, 2015
• Study Start: December 1, 2015
• Primary Completion: April 1, 2022
• Study Completion: May 1, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Locations

US (1)