Treatment for Affect Dimensions

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and targets of Positive Affect Treatment, a psychotherapy specifically aimed at enhancing reward sensitivity in individuals with low positive affect (a core feature of anhedonia) in the context of depression or anxiety. Target enrollment is 68 male and female participants with low positive affect and depression or anxiety and impaired functioning, between the ages of 18 and 65 years, who will be randomized to either Positive Affect Treatment or Negative Affect Treatment (designed to reduce threat sensitivity). Participants will complete laboratory tests, psychiatric assessments, and self-report questionnaires as part of the study. The total length of participation is around 4 months.

Detailed Description
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Low positive affect in the context of depression or anxiety has been relatively resistant to pharmacological and psychological treatments. Newer treatments that focus upon positivity or reward sensitivity have shown promising results. As an NIMH funded R61 phase trial, the purpose of the current randomized controlled trial is to evaluate the efficacy and targets of Positive Affect Treatment (designed to augment reward sensitivity) for individuals with low positive affect in the context of depression or anxiety symptoms. Targets include behavioral, cognitive, physiological and experiential measures of three reward processes: reward anticipation, response to reward attainment, and reward learning. Specificity of target engagement is assessed by comparison with Negative Affect Treatment, designed to reduce threat sensitivity. Clinical outcomes are assessed at baseline and either weekly or at Week 5, Week 10, and Week 15 (post). Targets are assessed at baseline, Week 5, Week 10, and Week 15. Statistical models evaluate whether change in outcomes and change in target measures are greater as a result of Positive Affect Treatment compared to Negative Affect Treatment and whether changes in target measures correlate with changes in outcome measures. Target enrollment is 68 male and female participants with low positive affect and depression or anxiety and impaired functioning between the ages of 18 and 65 who will be randomized to Positive Affect Treatment or Negative Affect Treatment, each comprising 15 individual psychotherapy sessions. Participants will complete laboratory tests and psychiatric assessments and self-report questionnaires as part of the study. Total length of participation is around 4 months.

Official Title
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Reward Sensitivity as a Mechanism of Positive Affect Treatment

Conditions
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Depression, Anxiety

Intervention / Treatment
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* Behavioral: Positive Affect Treatment
* Behavioral: Negative Affect Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: English-speaking Low positive affect indexed by less than or equal to 24 on the positive affect subscale of the PANAS (i.e., PANAS-P); and scores of greater than or equal to 11 for depression, greater to or equal to 6 for anxiety, or greater to or equal to 10 for stress on the Depression, Anxiety, and Stress Scale; and scores of greater than or equal to 5 on any Sheehan Disability Scale subscale. Willingness to refrain from starting other psychosocial or pharmacological treatments until study completion. Exclusion Criteria: Patient report of serious medical conditions - such as history of serious, uncontrolled medical illness, or instability (including significant cardio-pulmonary disease, organic brain syndrome, seizure disorder, cerebrovascular disease, thyroid dysfunction, and diabetes) Active suicidal ideation Lifetime history of bipolar disorder, psychosis, mental retardation, or organic brain damage Substance abuse in the last 6 months or dependence within last 12 months. 11 or more cigarettes per week or nicotine equivalent. History of marijuana, cocaine or stimulant use 5-7 times/week or more before age 15 (e.g., amphetamine, cocaine, methamphetamine) Pregnancy Bupropion, dopaminergic or neuroleptic medication use in the past 6 months Heterocyclics and SSRIs are permitted if stabilized (3 months) and PRN benzodiazepines and beta-blockers are permitted but discouraged on laboratory assessment visits Refusal of video/audio-taping

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Positive Affect Treatment<br>15 sessions of psychotherapy designed to augment reward anticipation, reward attainment, and reward learning. | Behavioral: Positive Affect Treatment<br>* Sessions 1-7: Pleasurable activities + imaginal recounting and reinforcement of positive mood effects (continued for sessions 8-15) Sessions 8-10: Cognitive exercises focusing on identifying positive aspects of experience, taking responsibility for positive outcomes, and imagining future positive events Sessions 11-14: Exercises to cultivate and savor positive experiences Session 15: Relapse prevention.<br>|
| Active Comparator: Negative Affect Treatment<br>15 sessions of psychotherapy designed to decrease threat avoidance, threat appraisal and arousal. | Behavioral: Negative Affect Treatment<br>* Sessions 1-7: Exposure therapy to feared or avoided situations, sensations, or memories (continued for sessions 8-15) Sessions 8-10: Cognitive restructuring of probability, cost, and attributional biases Sessions 11-14: Capnometry-assisted respiratory training Session 15: Relapse prevention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive Affect Subscale of the Positive and Negative Affect Scale (PANAS-P) | Reported positive affect. Scores can range from 10-50, with higher scores representing higher levels of positive affect. | Week 0, Week 5, Week 10, Week 16 | 
| Interviewer Anhedonia Ratings | Interviewer ratings of interest, pleasure, and motivation in hobbies/pastimes, foods/drinks, social activities (score range: 1-12), higher scores indicate lower anhedonia. | Week 0, Week 5, Week 10, Week 16 | 
| Depression Anxiety and Stress Scale (DASS-21) | Reported symptoms of depression, anxiety, and stress (score range: 0-63), higher scores indicate higher symptom severity and frequency. | Week 0, Week 5, Week 10, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sheehan Disability Scale (SDS) | Reported impairment due to symptoms (score range: 0-30) with higher scores indicating greater impairment. Includes reported number of days of missed school/work and number of days of reduced productivity. Statistical analyses have not yet been conducted for this outcome measure. | Week 0, Week 5, Week 10, Week 16 | 
| Beck Depression Inventory (BDI) | Reported suicidal ideation (item 9 on the BDI), scores range from 0-3 with higher scores indicating a higher degree of suicidal ideation. Statistical analyses have not yet been conducted for this outcome measure. | Week 0, Week 5, Week 10, Week 16 | 
| Daily Activity/Social Interaction (Actigraph) | We intended to collect data on energy expenditure over four 7-day periods (at week 0, week 5, week 10, and week 16) using a wrist-worn Actigraph tri-axial accelerometer. However, the use of Actigraph monitors was terminated early in the study due to the onset of the COVID-19 pandemic. | Week 0, Week 5, Week 10, Week 16 | 
| Effort Expenditure for Rewards Task (EEfRT) | The Effort Expenditure for Rewards Task (EEfRT) is a computer-based multi-trial task used to objectively assess decision-making and willingness to expend effort for reward. The dependent variable is the ratio of hard (high-effort) choices to the total number of trials. Results range from 0 to 1, with higher values indicating a higher proportion of hard (high-effort) choices. Results show the mean proportion of high-effort choices. | Week 0, Week 5, Week 10, Week 16 | 
| Monetary Incentive Task | Heart rate acceleration during the Monetary Incentive Task (MIT) was used to measure cardiac responding to the prospect of a monetary reward. The dependent variable is the interbeat interval acceleration during the task (score range in our sample: -0.16 to 0.17). Higher values indicate greater cardiac responding to the prospect of monetary reward. | Week 0, Week 5, Week 10, Week 16 | 
| Behavioral Inhibition/Behavioral Activation (Reward Drive Subscale) (BAS-RD) | Mediator: Reported reward sensitivity (score range: 4-16), with higher scores indicating higher sensitivity | Week 0, Week 5, Week 10, Week 16 | 
| Dimensional Anhedonia Rating Scale-Anticipation and Motivation Items | Mediator: Reported reward desire, motivation, and effort (score range: 0-76) with higher scores indicating higher degree of reward desire, motivation, and effort. | Week 0, Week 5, Week 10, Week 16 | 
| Dimensional Anhedonia Rating Scale-Consummatory Items | Mediator: Reported reward-related pleasure (score range: 0-28), with higher scores indicating higher degree of pleasure. | Week 0, Week 5, Week 10, Week 16 | 
| Modified Attentional Dot Probe Task-Disengagement Bias for Negative Stimuli | The Modified Attentional Dot Probe Task is a computer-based multi-trial task used to objectively assess attentional bias toward positively- and negatively-valenced stimuli. The dependent variable is the reaction time index for disengagement bias from sad faces. This is calculated as follows: (Cue appears proximal to emotional face in the pair of emotional face and random blur image: reaction time for target distal to emotional face minus reaction time for target proximal to emotional face) minus (Cue proximal to neutral face in pair of neutral face and random blur image: reaction time for target distal to neutral face minus reaction time for target proximal to neutral face). The range of values in our sample was: -309.28 to 283.45. | Week 0, Week 5, Week 10, Week 16 | 
| Modified Attentional Dot Probe Task-Engagement Bias for Positive Stimuli | The Modified Attentional Dot Probe Task is a computer-based multi-trial task used to objectively assess attentional bias toward positively- and negatively-valenced stimuli. The dependent variable is the reaction time index for engagement bias from happy faces. This is calculated as follows: (Cue probe distal to negative image in negative/abstract image pair: RT for target probe distal to negative image minus RT for target probe proximal to negative image) minus (Cue probe distal to neutral image in neutral/abstract image pair: RT for target probe distal to neutral image minus RT for target probe proximal to neutral image). The range of data in our sample was: -237.82 to to 343.93. Statistical analyses have not yet been conducted for this outcome measure. | Week 0, Week 5, Week 10, Week 16 | 
| International Affective Picture System Task | Heart rate acceleration during presentation of images from the International Affective Picture Systems (IAPS) was used to assess cardiac responding to positive images. The dependent variable is heart rate acceleration during the 6 seconds of positive image presentation relative to the last 2 seconds before picture onset. Higher values indicate greater cardiac responding to positive images. The range of values in our sample was: -0.12 to 0.09. | Week 0, Week 5, Week 10, Week 16 | 
| Temporal Experience of Pleasure Scale (Consummatory Subscale) | Mediator: Reported reward consummatory pleasure (score range: 8-48), with higher scores indicating higher reported reward consummatory pleasure | Week 0, Week 5, Week 10, Week 16 | 
| Probabilistic Reward Task (PRT) | The Probabilistic Reward Task (PRT) is a computer-based multi-trial task used to objectively assess the propensity to modulate behavior as a function of prior reinforcements. The dependent variable is response bias (measured as accuracy) toward the more frequently rewarded stimulus. A high response bias emerges when subjects show high rates of correct identification (hits) for the rich stimulus and high miss rates for the lean stimulus (i.e., the stimulus associated with less frequent rewards). Higher values indicate a greater propensity to modulate behavior as a function of prior reinforcements. The range of values in our sample was: -0.58 to 0.78. | Week 0, Week 5, Week 10, Week 16 | 
| Pavlovian Instrumental Transfer Task - Force (PIT-FORCE) | The Pavlovian Instrumental Transfer (PIT) task assesses the extent to which a conditional stimulus paired with reward influences instrumental responding to gain rewards. The dependent variable was handgrip force exerted in response to stimuli during a test phase following Pavlovian conditioning. Higher values indicate greater instrumental responding to gain rewards as a function of Pavlovian conditioning to a conditional stimulus paired with reward. The range of values in our sample was: -18.76 to 61.30. | Week 0, Week 5, Week 10, Week 16 | 
| Pavlovian Instrumental Transfer Task - Valence (PIT-VALENCE) | Within the Pavlovian Instrumental Transfer Task (PIT), participants rate the pleasantness (0-4) for three conditional stimuli to indicate the perceived value of reward associated with each one. The dependent variable is the self-reported pleasantness for rewarded stimuli compared to nonrewarded stimuli. This is calculated by first taking the average of participants' pleasantness ratings for the three CS+s and CS-s, and then subtracting the average CS- ratings from the average CS+ ratings. Higher values indicate greater responding to Pavlovian conditioning during the task. | Week 0, Week 5, Week 10, Week 16 |