Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Study 1.2 (Stress Manipulation)

Novel Treatment Targets For Affective Disorders Through Cross-Species Investigation of Approach/Avoidance Decision Making

This study investigates how remitted individuals with past major depressive disorder (MDD) make approach-avoidance decisions and which brain regions are implicated in such decisions. Information collected through MRI and behavioral tasks will be used to predict depressive symptoms in the future.

Study Overview

• Status: Recruiting
• Conditions: Major Depression in Remission
• Intervention / Treatment: Device: Aversive stimuli

Detailed Description

The overarching goals of this research are to investigate: (1) neural substrates of approach/avoidance behaviors in remitted MDDs; (2) stress-induced signaling in remitted individuals with past MDD; (3) neural markers that prospectively predict disease course.

This will be achieved through an innovative method of using functional magnetic resonance imaging (fMRI) during an approach/avoidance decision-making task.

• Study Type: Observational
• Enrollment (Estimated): 96

Contacts and Locations

• Study Contact: Name: David Crowley, ALM; Phone Number: 617-855-4432; Email: djcrowley@mclean.harvard.edu
• Study Contact Backup: Name: Emma Palermo, BA; Phone Number: 617-855-4412; Email: ehpalermo@mclean.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • Recruiting
      • McLean Hospital
      • Contact: David Crowley; Phone Number: 617-855-4432; Email: djcrowley@mclean.harvard.edu
      • Principal Investigator: Diego Pizzagalli, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The subjects for this research will be 96 participants recruited from the community by the Center for Depression, Anxiety and Stress Research (Director: Dr. Diego Pizzagalli, Ph.D.). Participants will include: (1) 48 participants with past MDD; and (2) 48 demographically matched healthy controls.

Description

Inclusion Criteria for all participants:

• All genders, races, and ethnic origins, aged between 18 and 45
• Capable of providing written informed consent, and fluent in English
• Right-handed
• Absence of any psychotropic medications for at least 2 weeks
• Has a smartphone (iPhone or Android) (needed for Ecological Momentary Assessment)

Inclusion Criteria for "Remitted MDD" group:

• Meets inclusion criteria for all subjects, plus:
• History of MDD as defined by DSM-5
• Absence of anxiety disorder for the past two months

Exclusion Criteria for all participants:

• Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician. These patients will be immediately referred to appropriate clinical treatment
• Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, or partner with vasectomy)
• Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
• History of seizure disorder
• History of psychiatric illnesses, other than depression or anxiety disorders among the Current MDD and Remitted MDD groups
• History of substance use disorder or alcohol use disorder (as these terms are defined by DSM-5); except depressed subjects may have a history of 'Mild' substance/alcohol use disorder only if it ended as least 12 months ago
• History of cocaine or stimulant use or dopaminergic drugs
• History or current diagnosis of dementia, or a score of < 26 on the Mini Mental State Examination at the screening visit;
• Patients with mood congruent or mood incongruent psychotic features
• Current use of other psychotropic drugs
• Clinical or laboratory evidence of hypothyroidism
• Patients with a lifetime history of electroconvulsive therapy (ECT)
• Failure to meet standard MRI safety requirements
• Abnormal ECG and lab results
• History of seizure disorder

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
remitted MDD; Unmedicated Remitted Participants with Past History of MDD	Device: Aversive stimuli; Electrotactile stimulation will be used as the aversive stimulus. The aversive stimulus is delivered in the form of a mild half-second stimulation to the ankle, calibrated to a subjective threshold that is uncomfortable but not painful. This stimulation is delivered by Digitimer DS8R Constant Current Stimulator (Digitimer North America, LLC. Ft. Lauderdale, FL). Its previous model DS71 has been safely implemented in studies with previously MGH-approved IRB's (Milad et al., 2013).; Other Names: no other name
Control subjects; healthy control subjects	Device: Aversive stimuli; Electrotactile stimulation will be used as the aversive stimulus. The aversive stimulus is delivered in the form of a mild half-second stimulation to the ankle, calibrated to a subjective threshold that is uncomfortable but not painful. This stimulation is delivered by Digitimer DS8R Constant Current Stimulator (Digitimer North America, LLC. Ft. Lauderdale, FL). Its previous model DS71 has been safely implemented in studies with previously MGH-approved IRB's (Milad et al., 2013).; Other Names: no other name

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Interview	For assessing psychological state	Baseline
Salivary Cortisol	For assessing stress level	Baseline
Behavioral Performance on the Probabilistic Reward Task (PRT)	The Probablilistic Reward Task assesses positive reinforcement learning.	Baseline
MRI Data	For testing the neural correlates of approach-avoidance decision making behaviors in a trans-diagnostic sample	MRI scans take place within 30 days of Screening Visit
Follow-up Clinical interviews	To assess psychological state changes	Change from Baseline at 6 months and 12 months after the MRI scanning visit

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Investigators: Principal Investigator: Diego Pizzagalli, PhD, McLean Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2021
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 24, 2020
• First Submitted That Met QC Criteria: March 26, 2020
• First Posted (Actual): March 27, 2020

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 2020A000886

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No