Neural Correlates of Stress and Perceived Control in Adolescent Depression

Lack of perceived control, particularly during stress, has been critically implicated in major depressive disorder (MDD) and anhedonic symptoms, especially among female adolescents; yet the neural underpinnings of perceived control disruptions in MDD remain poorly understood. Using functional magnetic resonance imaging with a novel "value of control task" in conjunction with a prospective design, this study will provide a comprehensive understanding of stress and perceived control related mechanisms in female adolescents with MDD and will examine stress-induced disruptions in perceived control as a predictor of "real world" expressions of maladaptive coping and anhedonia.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Behavioral: Computer Task Manipulation

Detailed Description

Participants in this research will include 40 female adolescents, aged 14-18, with Major Depressive Disorder (MDD) and 40 healthy adolescents from the greater Boston area by Dr. Emily Belleau, at McLean Hospital's Center for Depression, Anxiety and Stress Research.

The study will include four sessions:

• A clinical diagnostic interview as well as filling out a series of questionnaires and assessments.
• The second session will include a functional magnetic resonance imaging (fMRI) brain scan to be conducted at the McLean Hospital Imaging Center. Participants will be asked to respond to surveys on their cell phone in the week following the fMRI brain scan.
• The third session will include a diagnostic interview, assessments, and questionnaires to be completed three-months after the fMRI brain scan. Participants will be asked to complete surveys on their cell phone during the week following this three month follow-up session.
• The fourth session will include a diagnostic interview, assessments, and questionnaires to be completed six-months after the fMRI brain scan. Participants will be asked to complete surveys on their cell phone during the week following this six month follow-up session.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emily L Belleau, PhD; Phone Number: 6178554245; Email: ebelleau@mclean.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • Recruiting
      • McLean Hospital
      • Contact: Emily L Belleau, PhD; Phone Number: 617-855-4245; Email: ebelleau@mclean.harvard.edu
      • Principal Investigator: Emily L Belleau, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Inclusion Criteria: All Participants

  1. Females of all ethnic origins See Section: Inclusion of Women and Minorities);
  2. Ages 14-18 (See Section: Inclusion of Children);
  3. Written informed assent/consent from adolescent and parent/guardian (if under age 18);
  4. English as a first language or English fluency;
  5. Right handed111;
  6. Personal cell-phone (for Ecological Momentary Assessment [EMA]) 7 All participants will be in the follicular phase of their menstrual cycle when completing the functional magnetic resonance imaging (fMRI) study session

Inclusion Criteria: MDD Sample

1. Meet Diagnostic Statistical Manual-5th edition (DSM-5) diagnostic criteria for major depressive disorder (as diagnosed with the KSADS)
2. Absence of any psychotropic medications for at least 2 weeks (6 weeks for fluoxetine; 6 months for neuroleptics; 2 weeks for benzodiazepines; 2 weeks for any other antidepressants);

Inclusion Criteria: Healthy Control (HC) Sample

1. No history or current diagnosis of any DSM-5 psychiatric or substance/alcohol-related disorder (as diagnosed with the KSADS)
2. No first-degree relatives with a history of depression, bipolar disorder, or psychosis

Exclusion Criteria:

• Exclusion Criteria: All Participants

  1. History of head trauma with loss of consciousness;
  2. History of seizure disorder;
  3. Serious or unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease;
  4. History of cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine);
  5. History of use of dopaminergic drugs (including methylphenidate);
  6. Use of hormonal replacement therapy, anabolic steroids, or hormonal contraception;
  7. Clinical or laboratory evidence of hypothyroidism;
  8. Systemic medical or neurological illness that could impact fMRI measures of cerebral blood flow;
  9. Failure to meet standard exclusion criteria for fMRI scanning (e.g., claustrophobia, cardiac pacemakers, neural pacemakers, surgically implanted metal devices, cochlear implants, metal braces, or other metal objects in the body);
  10. Pregnancy
  11. Testing positive on a drug test on the day of the scan which testis for stimulants, marijuana, barbiturates, benzodiazepine, buprenorphine, 3,4-Methyl enedioxy methamphetamine (MDMA), methadone, opiates, oxycodone, phencyclidine;
  12. History of electroconvulsive therapy
  13. Participants with suicidal ideation where study participation is deemed unsafe by the study clinician;

Additional Exclusion Criteria: Major Depressive Disorder (MDD) Sample

1. Major depressive disorder diagnosis secondary to another disorder (selected comorbid anxiety disorders such as generalized anxiety disorder, specific phobia, and social anxiety disorders are allowed if they are secondary to MDD)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Computer Task Manipulation; Participants will complete computer tasks while undergoing an fMRI brain scan	Behavioral: Computer Task Manipulation; Participants will complete computer tasks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood-Oxygen-Level-Dependent Imaging (BOLD) activation of the ventral striatum and ventral medial prefrontal cortex	BOLD activation of frontostriatal regions in response to computer tasks performed during the fMRI Brian scan	1.5 hour long scan during session 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortisol Rating	Saliva rating to be collected throughout the fMRI brain scan	collected as part of 1.5 hour long scan during session 2
Mood Rating	Self-reported mood rating to be collected throughout the fMRI brain scan	collected as part of 1.5 hour long scan during session 2
Stress Reactivity Score	Stress Reactivity Survey Item collected via smart-phone delivered ecological momentary assessment	Longitudinal, three time points (baseline, 3-month follow-up, 6-month follow-up)
Stress Reactive Rumination Score	Stress Reactive Rumination Scale collected via smart-phone delivered ecological momentary assessment	Longitudinal, three time points (baseline, 3-month follow-up, 6-month follow-up)
Positive Affect Score	Positive Affect Survey Items collected via smart-phone delivered ecological momentary assessment	Longitudinal, three time points (baseline, 3-month follow-up, 6-month follow-up)

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Investigators: Principal Investigator: Emily L Belleau, PhD, McLean Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2021
• Primary Completion (Anticipated): April 30, 2025
• Study Completion (Anticipated): April 30, 2025

Study Registration Dates

• First Submitted: March 3, 2021
• First Submitted That Met QC Criteria: March 8, 2021
• First Posted (Actual): March 9, 2021

Study Record Updates

• Last Update Posted (Actual): April 22, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: neuroimaging; depression; stress; perceived control
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: K23MH122668 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No