Anhedonia
Conditions
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.
Interventions
BEHAVIORALBehavioral Activation
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.
Sponsors
National Institute of Mental Health (NIMH)
Mclean Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 18 Years
Healthy volunteers
Yes
Inclusion criteria
General 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anhedonic Adolescents Receiving Behavioral Activation 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 Activation: 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. | 39 |
| Non-Anhedonic Adolescents Adolescents without anhedonia (healthy controls) who did not receive behavioral activation | 41 |
| Total | 80 |
Baseline characteristics
| Characteristic | Anhedonic Adolescents Receiving Behavioral Activation | Total | Non-Anhedonic Adolescents |
|---|---|---|---|
| Age, Continuous | 15.7 years STANDARD_DEVIATION 1.9 | 15.9 years STANDARD_DEVIATION 1.9 | 16.2 years STANDARD_DEVIATION 1.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants | 77 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 7 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 32 Participants | 61 Participants | 29 Participants |
| Region of Enrollment United States | 39 participants | 80 participants | 41 participants |
| Sex: Female, Male Female | 26 Participants | 55 Participants | 29 Participants |
| Sex: Female, Male Male | 13 Participants | 25 Participants | 12 Participants |
| Snaith-Hamilton Pleasure Scale (SHAPS) | 36.18 SHAPS total score STANDARD_DEVIATION 5.85 | 26.79 SHAPS total score STANDARD_DEVIATION 10.45 | 17.85 SHAPS total score STANDARD_DEVIATION 3.91 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 80 |
| other Total, other adverse events | 0 / 80 |
| serious Total, serious adverse events | 2 / 80 |
Outcome results
Primary
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
Time frame: Change from pre-treatment (baseline) to post-treatment (12 weeks)
Population: Participants who completed pre- and post-treatment SHAPS (and corresponding timepoints for non-anhedonic control group who did not receive BA treatment)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral Activation | Change in Anhedonic (Snaith-Hamilton Pleasure Scale; SHAPS) Symptoms | 7.06 units on SHAPS scale | Standard Deviation 8.65 |
| Non-anhedonic Adolescent Control Group | Change in Anhedonic (Snaith-Hamilton Pleasure Scale; SHAPS) Symptoms | -1.29 units on SHAPS scale | Standard Deviation 3.57 |
Primary
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
Time frame: Change from pre-treatment (baseline) to post-treatment (12 weeks). Positive values reflect increases in neural response
Population: Participants who completed both baseline and post-treatment fMRI scan (corresponding timepoints for non-anhedonic group). See Neuropsychopharmacology (2023) 48:623-632; https://doi.org/10.1038/s41386-022-01481-4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Behavioral Activation | Change in Brain (Striatal and Medial PFC) Activation During a Monetary Reward Gambling Task | right striatrum | 0.35 Mean beta weights for ROI win > neutral | Standard Deviation 1.41 |
| Behavioral Activation | Change in Brain (Striatal and Medial PFC) Activation During a Monetary Reward Gambling Task | left striatum | -0.04 Mean beta weights for ROI win > neutral | Standard Deviation 1.16 |
| Behavioral Activation | Change in Brain (Striatal and Medial PFC) Activation During a Monetary Reward Gambling Task | medial pfc | -0.2 Mean beta weights for ROI win > neutral | Standard Deviation 0.9 |
| Non-anhedonic Adolescent Control Group | Change in Brain (Striatal and Medial PFC) Activation During a Monetary Reward Gambling Task | right striatrum | -0.31 Mean beta weights for ROI win > neutral | Standard Deviation 1.01 |
| Non-anhedonic Adolescent Control Group | Change in Brain (Striatal and Medial PFC) Activation During a Monetary Reward Gambling Task | left striatum | -0.49 Mean beta weights for ROI win > neutral | Standard Deviation 1.59 |
| Non-anhedonic Adolescent Control Group | Change in Brain (Striatal and Medial PFC) Activation During a Monetary Reward Gambling Task | medial pfc | -0.17 Mean beta weights for ROI win > neutral | Standard Deviation 1.31 |
Primary
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
Time frame: Change in reward learning from pre-treatment (baseline) to post-treatment (12 weeks).
Population: Participants with usable (passed quality control and not lost due to start of COVID) PRT data at pre- and post-assessment. See Webb et al, Neuropsychopharmacology (2023) 48:623-632; https://doi.org/10.1038/s41386-022-01481-4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral Activation | Change in Performance (Reward Learning) on the Probabilistic Reward Task (PRT) Computer Task | 0.08 reward learning score | Standard Deviation 0.18 |
| Non-anhedonic Adolescent Control Group | Change in Performance (Reward Learning) on the Probabilistic Reward Task (PRT) Computer Task | 0.1 reward learning score | Standard Deviation 0.2 |