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Translational Model of Anhedonia

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ClinicalTrials.gov Identifier: NCT03856177
Recruitment Status : Recruiting
First Posted : February 27, 2019
Last Update Posted : April 27, 2021
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
James Cavanagh, University of New Mexico

Brief Summary:
The proposed research addresses a major mental health issue (anhedonia) with a novel computationally-inspired translational technique in both humans and mice. This approach greatly increases the likelihood that a positive animal model result will be successfully translated to humans. This research plan thus offers a novel way to address the NIMH's mission of defining mechanisms of complex behaviors.

Condition or disease Intervention/treatment Phase
Anhedonia Behavioral: Emotion Induction Not Applicable

Detailed Description:
Although considered a trans-diagnostic phenotype, anhedonia can emerge from deficits in motivation, valuation, or hedonic appreciation, each of which reflect different neural processes and are differently expressed across individuals. There is a critical need to refine the construct of anhedonia in order to improve treatment. The long-term goal of this project is to combine computational, imaging, and causal manipulations to define a translational biomarker of diminished valuation in anhedonia. This proposal aims to identify how the EEG response known as the Reward Positivity (RewP) is a candidate biomarker specific to value-based deficiencies in anhedonia. The RewP is only elicited by the presentation of a rewarding outcome, it is decreased in depression, and it scales with the central feature of reinforcement learning models, the positive reward prediction error (+RPE). Importantly, this same neural response can be elicited in rodents using the same learning task as in humans. The objective of this proposal is to test whether induced emotion, depressed mood, and learned helplessness (in mice) directly diminish +RPE coding in the RewP. The rationale for this approach is that electrophysiology is a highly promising tool for identifying mechanisms of complex behaviors and translating these mechanisms between species. Aim 1 will determine if induced emotion and +RPE have independent or interactive effects on the RewP. Aim 2 will recruit depressed participants and determine if anhedonia and +RPE have independent or interactive influences on the source-level generators underlying the RewP (using MEG). Aim 3 will use the same task in a mouse model with infralimbic recordings; this will then test the causal diminishment (learned helplessness) and recovery (fluoxetine) of this mechanism. This proposed research is innovative because it identifies a computational function tightly tied to a neural response that directly addresses the disease-specific phenotype in human patients and is capable of being assessed, manipulated, and recovered within a rodent model. This contribution is expected to be significant because it will advance a translational mechanism for deficient valuation in anhedonia. Upon completion of these aims, the expected outcome will validate the RewP as a sensitive and specific mechanism of aberrant valuation in anhedonia. In line with the Research Domain Criteria framework, the use of computational modeling will facilitate algorithmic contrasts between multiple sub-constructs of approach motivation in the positive valence systems domain. The translational computational psychiatry approach advanced here links circuit-level dysfunction, aberrant computations, and trans-diagnostic behavioral phenotype. The successful completion of the aims advanced here will create a highly promising path for combining these strengths into a computationally-inspired, mechanistically tested, translatable model of aberrant valuation in anhedonia. This novel candidate biomarker will be translatable between species and testable in an outpatient clinic.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be randomly assigned into neutral or emotionally evocative conditions prior to assessing EEG brain signals of reward.
Masking: Single (Investigator)
Masking Description: Randomization will be based on the last digit (odd vs. even) of the participant's research identifier.
Primary Purpose: Basic Science
Official Title: A Novel Bench-to-Bedside Translational Model of Anhedonia
Actual Study Start Date : April 1, 2019
Estimated Primary Completion Date : March 31, 2024
Estimated Study Completion Date : March 31, 2024

Arm Intervention/treatment
Experimental: Neutral
A neutral mood induction will include reading a dull text while listening to non-evocative music for 5-15 minutes.
Behavioral: Emotion Induction
Described in arm

Experimental: Evocative
A mood induction procedure will be utilized. The procedure consists of a combination of re-experiencing an autobiographical sad personal event while listening to their choice of one of four sad music selections commonly used in mood induction. Visual analogue scale ratings will assess momentary sadness prior to, following, and at subsequent time points around the mood induction procedure.
Behavioral: Emotion Induction
Described in arm




Primary Outcome Measures :
  1. Reward Positivity Component of the Event-Related Electroencephalogram [ Time Frame: There will only be one day session (on the date of the randomization) where the Reward Positivity amplitude is assessed ]
    The Reward Positivity is a fronto-centrally located positive voltage burst recorded in the EEG from about 200-500 ms following the receipt of a reinforcing outcome (e.g. money, points).



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men or women aged 18-55
  • Free from psychoactive medication for at least 2 weeks

Exclusion Criteria:

  • Participants unwilling or unable to give informed consent
  • Presence of other known medical or psychiatric comorbidity that in the investigator's opinion would compromise participation in the study
  • History of psychosis
  • Not fluent in English

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03856177


Contacts
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Contact: James F Cavanagh, PhD 415-867-0303 jcavanagh@unm.edu
Contact: Davin Quinn, MD dquinn@salud.unm.edu

Locations
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United States, New Mexico
University of New Mexico - Logan hall Recruiting
Albuquerque, New Mexico, United States, 87106
Contact: james F Cavanagh, PhD         
Sponsors and Collaborators
University of New Mexico
National Institute of Mental Health (NIMH)
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Responsible Party: James Cavanagh, Assistant Professor, University of New Mexico
ClinicalTrials.gov Identifier: NCT03856177    
Other Study ID Numbers: 1R01MH119382-01 ( U.S. NIH Grant/Contract )
First Posted: February 27, 2019    Key Record Dates
Last Update Posted: April 27, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anhedonia
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases