Neural Correlates of Stress and Perceived Control in Adolescent Depression

Overview

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.

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.

Interventions

• Behavioral Computer Task Manipulation
  Participants will complete computer tasks.

Primary outcome measures

• Blood-Oxygen-Level-Dependent Imaging (BOLD) activation of the ventral striatum and ventral medial prefrontal cortex [Time frame: 1.5 hour long scan during session 2]

Secondary outcome measures (5)

• Cortisol Rating [Time frame: collected as part of 1.5 hour long scan during session 2]
• Mood Rating [Time frame: collected as part of 1.5 hour long scan during session 2]
• Stress Reactivity Score [Time frame: Longitudinal, three time points (baseline, 3-month follow-up, 6-month follow-up)]
• Stress Reactive Rumination Score [Time frame: Longitudinal, three time points (baseline, 3-month follow-up, 6-month follow-up)]
• Positive Affect Score [Time frame: Longitudinal, three time points (baseline, 3-month follow-up, 6-month follow-up)]

Eligibility criteria

Inclusion criteria

• Inclusion Criteria: All Participants

• Females of all ethnic origins See Section: Inclusion of Women and Minorities);
• Ages 14-18 (See Section: Inclusion of Children);
• Written informed assent/consent from adolescent and parent/guardian (if under age 18);
• English as a first language or English fluency;
• Right handed111;
• 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

• Meet Diagnostic Statistical Manual-5th edition (DSM-5) diagnostic criteria for major depressive disorder (as diagnosed with the KSADS)
• 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

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

Exclusion criteria

• Exclusion Criteria: All Participants

• History of head trauma with loss of consciousness;
• History of seizure disorder;
• Serious or unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease;
• History of cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine);
• History of use of dopaminergic drugs (including methylphenidate);
• Use of hormonal replacement therapy, anabolic steroids, or hormonal contraception;
• Clinical or laboratory evidence of hypothyroidism;
• Systemic medical or neurological illness that could impact fMRI measures of cerebral blood flow;
• 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);
• Pregnancy
• 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;
• History of electroconvulsive therapy
• 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 1 center

• McLean Hospital — Belmont

Identifiers

NCT: NCT04788524 · K23MH122668

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗