Early Life Stress and Depression: Molecular and Functional Imaging

Last updated: October 28, 2024
Sponsor: Mclean Hospital
Overall Status: Active - Recruiting

Phase

N/A

Condition

Depression

Treatment

N/A

Clinical Study ID

NCT04713722
2020P001470
  • Ages 20-32
  • Female
  • Accepts Healthy Volunteers

Study Summary

Severe childhood adversity accounts for a large portion of psychiatric illness, and an increased risk for major depressive disorder (MDD). For some individuals, childhood adversity has negative psychological and medical consequences; others preserve mental and physical health despite such experiences (they are resilient). In spite of this, little is known about the neurobiological mechanisms related to childhood adversity, especially oxidative stress abnormalities in the brain. To fill this gap, this study combines functional, structural, and molecular imaging approaches to examine the role of oxidative stress abnormalities related to childhood adversity.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Females of all races and ethnic origins

  • Ages from 20 to 32

  • Right-handed

  • Capable of providing written informed consent

  • Currently unmedicated. Note that this criterion applies at enrollment only, andsubjects will be informed that they can continue to be in the study if they begin anew medication after enrollment.

  • Normal or corrected-to-normal vision and hearing

  • Fluency in written and spoken English

  • Absence of first-degree relatives with a history of a psychotic disorder orpsychotic symptoms; (adopted individuals are eligible to participate but we willprobe about family history in case such information is available to the adoptedsubject)

Exclusion

Exclusion Criteria:

  • Participants with suicidal ideation where continued study participation is deemedunsafe by the study clinician (these participants will be immediately referred toappropriate clinical treatment)

  • Pregnant women, or women of childbearing potential who have a positive result on aurine pregnancy test

  • Failure to meet MRI safety requirements including but not limited to any metalimplants or prostheses that cannot be removed, or exposure to shrapnel

  • Claustrophobia or severe anxiety that might impact participation in neuroimaging

  • Injury or movement disorder that may make it difficult to lie still in the scanner

  • Any current recreational/illicit drug use as assessed by a urine drug test (coveringcocaine, cannabinoids, opiates, amphetamines, methamphetamines, phencyclidine, MDMA,benzodiazepines, methadone, oxycodone, tricyclic antidepressants, and barbiturates)

  • Use of drug or herbal supplement for depression (e.g., St. John's Wort or SAMe) ofthose that could affect stress response

  • Use of any medication in the 24 hours prior to the Scanning procedure (includingantibiotics, asthma inhalants, pain relievers, antihistamines, or over-the-countermedications).

  • Recent use (within 3 weeks) or any medication that affects blood flow or bloodpressure, or which is vasodilating/vasoconstricting

  • Use of Melatonin within 5 days of the Scanning procedure

  • Metformin use in the past 6 months (for either clinical care or as part of research)

  • Serious or unstable medical illness, including cardiovascular, hepatic, renal,respiratory, endocrine (hypothyroidism), neurologic, autoimmune disease (such asLyme, Crohn's), or hematologic disease

  • Current infectious illness (either transient or chronic); Current episode ofallergic reaction or asthma

  • Hemophilia; Diabetes with poor glucose control; History of chronic migraine (> 15days/mo.); History or current diagnosis of dementia

  • History of seizure disorder

  • Any history of significant head injury or concussion

  • Past/current DSM-5 diagnosis of: OCD, ADHD, schizophrenia, schizoaffective disorder,delusional disorder, psychotic disorders NOS, bipolar disorder, patients with moodcongruent or mood incongruent psychotic features, autism or any other pervasivedevelopmental disorder, organic mental disorder, anorexia, binge eating disorder orbulimia (however a history of bulimia or binge eating disorder is allowable if ithas been in remission for at least two years)

  • History of moderate or severe substance or alcohol use disorder; or, mild substanceor alcohol use disorder within the last 12 months (with the exception of cocaine orstimulant abuse, which will lead to automatic exclusion).

  • History of ECT

  • Patient is clinically unstable, in the judgment of the clinician

Study Design

Total Participants: 160
Study Start date:
February 01, 2021
Estimated Completion Date:
April 01, 2025

Study Description

Epidemiological studies have shown that severe childhood adversity explains 32-44% of psychiatric disorders, and is associated with 4.6-fold risk for MDD later in life. In spite of these epidemiological data, the neurobiological underpinnings associated with maladaptive sequelae of severe childhood adversity as well as resilience remain largely unknown.

Preclinical research suggests that early adversity leads to (1) structural abnormalities in brain regions critically implicated in stress regulation; (2) increased oxidative stress; and (3) glutamatergic abnormalities. The current research protocol is designed to prospectively test the contributions of these abnormalities in individuals exposed to severe childhood adversity.

Improving our understanding of neurobiological mechanisms associated with different childhood adversity outcomes is of paramount importance in order to (1) identify individuals at risk for psychopathology and maladaptive behavior, (2) prevent re-victimization, and (3) develop more targeted therapeutic interventions.

Connect with a study center

  • McLean Hospital

    Belmont, Massachusetts 02478
    United States

    Active - Recruiting

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