DepressionELSNCT04713722
Early Life Stress and Depression: Molecular and Functional Imaging
An observational study of Depression and Trauma, Psychological, run by Mclean Hospital at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 to 32 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Depression, Trauma, Psychological
- How many people
- 160 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2021to 30 Apr 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 32 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: Healthy controls, those with depression (current or remitted), and those with depression and history of childhood adversity
Who may be able to join
- 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, and subjects will be informed that they can continue to be in the study if they begin a new 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 or psychotic symptoms; (adopted individuals are eligible to participate but we will probe about family history in case such information is available to the adopted subject)
Who cannot join
- Participants with suicidal ideation where continued study participation is deemed unsafe by the study clinician (these participants will be immediately referred to appropriate clinical treatment)
- Pregnant women, or women of childbearing potential who have a positive result on a urine pregnancy test
- Failure to meet MRI safety requirements including but not limited to any metal implants 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 (covering cocaine, cannabinoids, opiates, amphetamines, methamphetamines, phencyclidine, MDMA, benzodiazepines, methadone, oxycodone, tricyclic antidepressants, and barbiturates)
Show all 20Show fewer
- Use of drug or herbal supplement for depression (e.g., St. John's Wort or SAMe) of those that could affect stress response
- Use of any medication in the 24 hours prior to the Scanning procedure (including antibiotics, asthma inhalants, pain relievers, antihistamines, or over-the-counter medications).
- Recent use (within 3 weeks) or any medication that affects blood flow or blood pressure, 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 as Lyme, Crohn's), or hematologic disease
- Current infectious illness (either transient or chronic); Current episode of allergic reaction or asthma
- Hemophilia; Diabetes with poor glucose control; History of chronic migraine (> 15 days/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 mood congruent or mood incongruent psychotic features, autism or any other pervasive developmental disorder, organic mental disorder, anorexia, binge eating disorder or bulimia (however a history of bulimia or binge eating disorder is allowable if it has been in remission for at least two years)
- History of moderate or severe substance or alcohol use disorder; or, mild substance or alcohol use disorder within the last 12 months (with the exception of cocaine or stimulant abuse, which will lead to automatic exclusion).
- History of ECT
- Patient is clinically unstable, in the judgment of the clinician
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
McLean Hospital
Belmont, Massachusetts, 02478
David Crowley, 617-855-4432, djcrowley@mclean.harvard.edu
Diego Pizzagalli, PhD
About this study
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.
Read the detailed 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.
- Conditions
- Depression, Trauma, Psychological
- Medical subject headings
- Depression, Psychological Trauma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| MDD/childhood adversity group | subjects with current MDD who experienced childhood adversity | |
| rMDD/ childhood adversity | subjects with a history of MDD who experienced childhood adversity | |
| MDD | subjects in a current episode of MDD, with no history of childhood adversity | |
| Healthy Control | healthy control subjects, with no history of childhood adversity |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immuno-oxidative abnormalities
Redox ratio and glutamate metabolites in the prefrontal cortex
Measured: Baseline
Secondary outcomes (3)
Blood oxygen level dependent (BOLD) activation
Prefrontal cortex activation during a reward task
Measured: Baseline
Blood oxygen level dependent (BOLD) activation in emotional processing
Prefrontal cortex activation during an emotional processing task
Measured: Baseline
Peripheral inflammation
Stress-related pro-inflammatory transcription control pathways
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2021
- Study start1 Feb 2021
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mclean Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Diego Pizzagalli, Mclean Hospital
- Investigators
- Diego Pizzagalli, PhD, Principal investigator, Mclean Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04713722
- Sponsor's protocol ID
- 2020P001470
- Acronym
- ELS
- Status last verified
- Oct 2026
- First submitted
- 14 Jan 2021
- Last updated
- 2 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Life Stress and Depression: Molecular and Functional Imaging
- ClinicalTrials.gov ID
- NCT04713722
- Acronym / sponsor ID
- ELS / 2020P001470
- Conditions
- Depression, Trauma, Psychological
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Mclean HospitalUniversity, hospital or other
- Study start
- 1 Feb 2021 (actual)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 19 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MDD/childhood adversity group | – | –subjects with current MDD who experienced childhood adversity |
| rMDD/ childhood adversity | – | –subjects with a history of MDD who experienced childhood adversity |
| MDD | – | –subjects in a current episode of MDD, with no history of childhood adversity |
| Healthy Control | – | –healthy control subjects, with no history of childhood adversity |
Who may qualify
- Ages
- 20 to 32 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Healthy controls, those with depression (current or remitted), and those with depression and history of childhood adversity
Key inclusion criteria (8 listed)
- 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, and subjects will be informed that they can continue to be in the study if they begin a new medication after enrollment.
Key exclusion criteria (20 listed)
- Participants with suicidal ideation where continued study participation is deemed unsafe by the study clinician (these participants will be immediately referred to appropriate clinical treatment)
- Pregnant women, or women of childbearing potential who have a positive result on a urine pregnancy test
- Failure to meet MRI safety requirements including but not limited to any metal implants 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Immuno-oxidative abnormalities
Time frame: Baseline
Redox ratio and glutamate metabolites in the prefrontal cortex
3 secondary outcomes
Blood oxygen level dependent (BOLD) activation
Time frame: Baseline
Blood oxygen level dependent (BOLD) activation in emotional processing
Time frame: Baseline
Peripheral inflammation
Time frame: Baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
Related trials for Depression
Recruiting
Unified Protocol in Penitentiary Facilities
Depression Disorders, Anxiety
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
Not yet recruitingObservational study
Functional Impact of Psychological Symptoms in Patients With Superior Semicircular Canal Dehiscence Syndrome (SSCD): a National Cross-sectional Study
Superior Semicircular Canal Dehiscence
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Recruiting
Cultural Adaptation of an Online Parenting Intervention to Reduce the Risk of Depression and Anxiety in Adolescents
Risk of Depression and Anxiety
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Diego Pizzagalli, PhD principal investigator
Mclean Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Depression and Trauma, Psychological, run by Mclean Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Aliza Brown (617-855-2589, abrown98@mclean.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immuno-oxidative abnormalities (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.