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

Not Applicable

Active, not recruiting

• Conditions: Anhedonia

• Registration Number: NCT02498925
• Lead Sponsor: Mclean Hospital

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.

Detailed Description

Participants in this research will include 35 anhedonic adolescents and 35 demographically matched healthy participants recruited from the greater Boston community by Dr. Webb at McLean Hospital's Center for Depression, Anxiety and Stress Research. The anhedonic adolescents will undergo 12 weeks of Behavioral Activation therapy. This study will include three sessions:

* The first session will involve a diagnostic interview, and a series of questionnaires and assessments.

* The second session will take place at the McLean Hospital's Neuroimaging Center, and involve an fMRI brain scan and administration of two behavioral tasks, as well as questionnaires.

* Following the 12-weeks treatment, anhedonic adolescents will return to McLean Hospital's Neuroimaging Center for an fMRI brain scan, two behavioral tasks, and questionnaires. The healthy control group will complete the same three assessments at corresponding time points.

Study Timeline

• Study First Submitted: 2015-07-10
• Study First Submitted QC: 2015-07-13
• Study First Posted: 2015-07-15
• Study Start: 2015-12
• Primary Completion: 2022-04
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-19
• Last Update Posted: 2023-01-20
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• 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

General

Exclusion Criteria

• 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
• Meet standard exclusion criteria for fMRI scanning (e.g. claustrophobia, cardiac pacemakers, neural pacemakers, surgically implanted metal devices, cochlear implants, metal braces, or other metal objects in their body);
• Positive urine pregnancy test

A. Anhedonic Adolescents:

Additional Exclusion Criteria:

• 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:

Additional Exclusion Criteria:

• Elevated depressive symptoms as assessed in phone screen
• History of meeting criteria for any DSM-5 psychiatric or substance-related disorder
• Use of any psychiatric medications
• Family history (first-degree relatives) of any psychiatric disorder

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Change in Anhedonic (Snaith-Hamilton Pleasure Scale; SHAPS) Symptoms	Change from pre-treatment (baseline) to post-treatment (12 weeks)	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 in Brain (Striatal and Medial PFC) Activation During a Monetary Reward Gambling Task	Change from pre-treatment (baseline) to post-treatment (12 weeks). Positive values reflect increases in neural response	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 in Performance (Reward Learning) on the Probabilistic Reward Task (PRT) Computer Task	Change in reward learning from pre-treatment (baseline) to post-treatment (12 weeks).	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

Trial Locations

Locations (1)

McLean Hospital; 🇺🇸 Belmont, Massachusetts, United States