Anhedonia, Development, and Emotions: Phenotyping and Therapeutics

Summary

The goal of the ADEPT Study is to understand anhedonia in young people and how it changes based on treatments targeting the brain circuit underlying it. Anhedonia is a challenging mental health symptom that involves difficulty with motivation to experience pleasant events. This study could help develop treatments for people whose depression does not improve with traditional treatments.

The ADEPT Study includes two phases. In Phase 1, participants are asked to go through a series of activities to measure anhedonia, including MRI scans, blood draws, behavioral tasks, clinical interviews, questionnaires, and app-based assessments of experiences and behaviors. Phase 2 involves therapeutic activities, such as transcranial magnetic stimulation (TMS), positive affect training, and, for some people, ketamine administration. If the participant qualifies and is interested, they may choose to do Phase 2 activities in addition to Phase 1.

Conditions

• Depression
• Anhedonia

Interventions

DEVICE

Continuous theta burst stimulation (cTBS)

a form of transcranial magnetic stimulation, to dorsomedial prefrontal cortex (dmPFC)

BEHAVIORAL

Positive Affect Training

Psychosocial add-on intervention that could enhance the effects of TBS. PA Therapy (Craske et al., 2016) is an innovative cognitive and experiential technique developed to address anhedonia specifically and, ideally, change altered patterns of frontostriatal function. Standing in contrast to Cognitive Behavioral Therapy, PA training has efficacy for enhancing positive affect and reducing negative affect (Craske et al., 2018). This treatment can be easily applied, and we propose that it will enhance neural circuit-level changes elicited by TBS.

DRUG

Ketamine Injectable Solution

Ketamine is FDA-approved as an anesthetic agent that will be used off-label in this study. It is used routinely in both pediatric and adult patients and is considered extremely safe in substantially higher, anesthetic doses. The dose to be administered here (0.5 mg/kg) is a much lower, subanesthetic dose, and the administration route (intravenous) is the standard when used in anesthesia. Published studies and metaanalyses of this dose of intravenous ketamine as an off label use in depression show clearly that there are no increased risks in this population, including a recent study in adolescents (Dwyer et al, 2021, American Journal of Psychiatry). A single dose of ketamine will be used to determine if it alters the functioning of the anhedonia-related reward functioning and frontostriatal biomarkers assessed in this study.

Sponsors & Collaborators

• Erika Forbes

  lead OTHER

Principal Investigators

• Erika E Forbes, PhD · University of Pittsburgh

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

15 Years

Max Age

25 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-07-22

Primary Completion

2024-12-19

Completion

2025-06-01

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations