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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Anhedonia

Intervention / Treatment
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* Behavioral: Behavioral Activation


Participation Criteria
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Eligibility Criteria
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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 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

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Behavioral Activation<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in anhedonic (SHAPS) symptoms |  | Change from pre-treatment (baseline) to post-treatment (12 weeks) | 
| Change in brain (striatal and medial PFC) activation during a monetary reward gambling task |  | Change from pre-treatment (baseline) to post-treatment (12 weeks) | 
| Change in performance (reward learning) on a probabilistic reward learning computer task |  | Change from pre-treatment (baseline) to post-treatment (12 weeks) |