Anxiety, Anxiety Disorders, Depression, Social Disconnection
Conditions
Keywords
Pramipexole, Anxiety, Depression
Brief summary
This study seeks to understand if the medication pramipexole improves social connectedness and functioning in adults (ages 18-50) who experience anxiety or depression. The study plans to enroll 108 participants total across two sites (University of California San Diego and New York State Psychiatric Institute). Pramipexole will be given in a 6-week randomized, double-blind, placebo-controlled trial. Social reward processing will be assessed using measures of brain function (fMRI), behavior, and self-report at baseline and week 6. Knowledge gained from this study will help determine the therapeutic potential of targeting the dopamine system to remediate social disconnection as an anxiety and depression intervention.
Detailed description
This study seeks to understand how modulating functioning of the neurotransmitter dopamine affects brain circuits, behaviors, and subjective experiences that are believed to underlie an individual's motivation to establish and maintain positive social connections. This knowledge will help advance understanding of brain mechanisms that can be used to better treat social functioning impairments in people experiencing anxiety or depression. The R61 phase project will evaluate the effects of pramipexole (a medication that increases dopamine signaling in the brain) on responses to different types of positive social cues or contexts. The study drug will be given in a 6-week randomized, double-blind, placebo-controlled trial for individuals with clinical levels of anxiety or depression. Aim 1 will test the hypothesis that pramipexole increases the anticipation of social rewards compared to placebo. Aim 2 will determine which dose of pramipexole (1.0 or 2.5 mg/d) produces a greater effect on social reward anticipation. To achieve these aims, approximately 108 participants (ages 18-50) with clinically elevated anxiety or depression will be randomized across two sites and randomized in equal proportions to one of two doses of pramipexole (1.0 mg/d or 2.5 mg/d) or placebo. They will complete standardized paradigms assessing social reward processing using measures of brain function (fMRI), behavior, and self-report at baseline and week 6. Knowledge gained from this study will help determine the therapeutic potential of targeting the dopamine system to remediate social disconnection.
Interventions
DRUGPramipexole Pill
The study drug, pramipexole, is an FDA-approved medication for the treatment of Parkinson's and restless leg syndrome. Pramipexole (Mirapex) tablets are taken orally, with or without food.
DRUGPlacebo Pill
Placebo will match the study drug in mode of administration, color, size, and taste.
Sponsors
National Institute of Mental Health (NIMH)
New York State Psychiatric Institute
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The pharmacy will blind drug and placebo through identical encapsulation. Placebo will match the study drug in mode of administration, color, size, and taste.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. Clinically elevated levels of anxiety (OASIS ≥ 8) or depression or (PHQ-9 ≥ 10). 2. Moderate or greater social disability assessed with clinician-rating (SDS - Social ≥ 5). 3. Below the normative mean for temperamental reward sensitivity (ATQ - Approach \< 35). 4. Age 18-50. 5. Ability to provide written informed consent. 6. English proficiency.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neural activation during social reward anticipation | Baseline, week 6 | The primary outcome of interest is blood oxygen level dependent (BOLD) response during anticipation of positive valence social cues vs. baseline in the striatum region of interest (ROI) mask, defined according to a meta-analysis of the social incentive delay task. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positive affect in response to the social affiliation task | Baseline, week 6 | The state version of the Positive and Negative Affect Schedule (PANAS) will be used to measure current (right now) positive affect before (anticipatory) and after (responsiveness) the social affiliation task. Items are answered on a 5 point scale, 1 (Very slightly or not at all) to 5 (Extremely). The positive affect scale ranges from 10-50; higher scores indicate greater levels of positive affect. |
| Social approach goals during the social affiliation task | Baseline, week 6 | Participants will rate 5 items describing approach-oriented goals focused on obtaining positive outcomes during the interaction. Items are answered on a 7-point scale with anchors of not at all and very much with higher scores indicating greater social approach goals. |
| Social approach behavior during the social affiliation task | Baseline, week 6 | Observers will rate participant behavior on self-disclosure (the degree of personal information, thoughts, and feelings revealed) and responsiveness (verbal and nonverbal displays reflecting understanding, engagement, and validation). Items are answered on a 7 point scale, 1 (not at all) to 7(very much) with higher scores indicating greater levels of social approach behavior. |
| Future approach motivation | Baseline, week 6 | The Desire for Future Interaction Scale (DFI) measures the degree to which respondents would be willing to affiliate with their conversation partner again. Items are answered on a 7 point scale, 1 (not at all) to 7 (very much) with higher scores indicating higher levels of future approach motivation. |
| Blood plasma pramipexole concentrations | Week 6 | — |
| Neural activation during opportunities to disclose to others | Baseline, week 6 | Blood oxygen level dependent (BOLD) response in the striatum region of interest (ROI) mask, defined according to a meta-analysis of the social incentive delay task, during share vs. private conditions of the disclosure task. |
| Motivation to engage in shared experiences with others | Baseline, week 6 | Participants will make choices about whether to watch the same (Shared) vs. a different (Solo) videoclip from their partner. Each option is paired with a small monetary payoff that varies across options and trials. The point of subjective equivalence will be used to quantify the relative payoff difference at which people are indifferent to the two options (0 = maximizing monetary payoff; scores \< 0 represent greater value assigned to sharing experiences). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Social avoidance goals during the social affiliation task | Baseline, week 6 | Participants will rate 5 items describing avoidance-oriented goals focused on avoiding negative outcomes during the interaction. Items are answered on a 7-point scale with anchors of not at all and very much with higher scores indicating greater social avoidance goals. |
| Anxious behavior during the social affiliation task | Baseline, week 6 | Observer-rated participant behavior during the social affiliation task using items reflecting the anxiety-related behaviors commonly displayed during social-evaluative stress (e.g., fidget, appear tense or rigid). Items are rated on a 7-point scale from not at all to very much. Higher scores reflect greater anxious behavior. |
| Negative affect in response to the social affiliation task | Baseline, week 6 | The state version of the Positive and Negative Affect Schedule (PANAS) will be used to measure current (right now) negative affect before (anticipatory) and after (responsiveness) the social affiliation task. Items are answered on a 5 point scale, 1 (Very slightly or not at all) to 5 (Extremely). The negative affect scale ranges from 10-50; higher scores indicate greater levels of negative affect. |
| Neural activation during social punishment anticipation | Baseline, week 6 | Blood oxygen level dependent (BOLD) response during anticipation of negative valence social cues vs. baseline in the anterior insula and amygdala region of interest (ROI) mask, defined according to a meta-analysis of the social incentive delay task. |
Countries
United States
Contacts
Primary ContactNuzhat Beg, MBBS, MAS
Backup ContactTaylor Smith, B.S.
Outcome results
None listed