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Depression, Adversity, and Stress Hormones (DASH) Study (DASH)

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ClinicalTrials.gov Identifier: NCT03195933
Recruitment Status : Completed
First Posted : June 22, 2017
Last Update Posted : June 22, 2017
Sponsor:
Collaborators:
National Institute of Mental Health (NIMH)
Brain & Behavior Research Foundation
Information provided by (Responsible Party):
University of Wisconsin, Madison

Brief Summary:

The stress-related hormone cortisol has been studied in depression for decades. However, relatively little is known about the role of cortisol in psychological features of depression. Basic research shows that cortisol modulates brain processes that are highly relevant to depression (especially the neural substrates of negative biases in learning and memory formation). However, very few studies have directly examined the effects of cortisol on neural circuitry of learning in depressed humans. In addition, the effects of cortisol on the neural substrates of learning differ for males and females. The toll of depression is especially high in women, who are roughly twice as likely as men to suffer from depression. Thus, the primary goal of this project is to investigate the effects of cortisol on the neural circuitry of learning in depressed women.

A secondary goal is to investigate whether early life adversity moderates cortisol's effects on the neural circuitry of learning. Animal data suggests that early life adversity causes life-long biases toward learning in threatening conditions associated with elevated cortisol. In addition, new data from humans suggests that alterations in cortisol traditionally ascribed to depression may stem in part from early adversity rather than depression per se. Thus, this study will examine effects of cortisol on the neural circuitry of learning in depressed and healthy women with and without history of early life adversity.

The study will use pharmacological manipulation of cortisol levels (compared to placebo) during measurement of brain activity at rest and during memory encoding of emotional and neutral stimuli. The study will also measure whether cortisol alters the negative biases in emotional memory often seen in depression. In doing so, the study will examine the role of cortisol in neural networks associated with emotional learning that are often implicated in depression.

Medications that target cortisol receptors in the brain may be beneficial in the treatment of depression. However, this knowledge has yet to inform clinical practice, and mechanisms of action of these medications are not well understood. This project is significant because it provides the prerequisite knowledge (and develops a paradigm) that can be used in the future in the development of more effective targeted intervention strategies.


Condition or disease Intervention/treatment Phase
Depression Other: Cortisol Other: Placebo Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 85 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Learning, Neural Signaling of Cortisol, and Early Adversity in Depression
Actual Study Start Date : July 31, 2013
Actual Primary Completion Date : May 19, 2016
Actual Study Completion Date : May 19, 2016


Arm Intervention/treatment
Experimental: Cortisol first, Placebo second
Single oral administration of 20 mg cortisol capsule to pharmacologically elevate cortisol levels during first functional magnetic resonance imaging (fMRI) session; Identically appearing placebo capsule during second fMRI session.
Other: Cortisol
We compared placebo vs. 20 mg oral dose of cortisol, which pharmacologically elevated cortisol levels.

Other: Placebo
We compared placebo vs. 20 mg oral dose of cortisol, which pharmacologically elevated cortisol levels.

Experimental: Placebo first, Cortisol second
Placebo capsule during first fMRI session; Single oral administration of 20 mg cortisol capsule to pharmacologically elevate cortisol levels during second fMRI session.
Other: Cortisol
We compared placebo vs. 20 mg oral dose of cortisol, which pharmacologically elevated cortisol levels.

Other: Placebo
We compared placebo vs. 20 mg oral dose of cortisol, which pharmacologically elevated cortisol levels.




Primary Outcome Measures :
  1. Emotional Memory after Cortisol Administration [ Time Frame: 15 minute memory assessment that takes place 2 days after cortisol administration MRI scan visit ]
    Memory for emotional pictures encoded during the cortisol administration MRI scan


Secondary Outcome Measures :
  1. Neural Function [ Time Frame: 90 minute scan session ]
    MRI



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Female
  • 18 to 45 years of age
  • English fluency
  • Able to lie still on their back for up to 90 minutes
  • Willing and able to return for all visits
  • Able to provide written informed consent prior to participation
  • In good physical health as determined on basis of medical history
  • If a nicotine user, able to refrain from nicotine use for 2 hours prior to fMRI scanning and throughout the scan visits
  • Additional criteria for never-depressed participants: Free of current or past Diagnostic and Statistical Manual (DSM) IV diagnoses of Major Depressive Disorder (MDD), Dysthymia, or other Depressive Disorder. Never-depressed participants may have past or current psychopathology other than depressive disorders that does not cause significant impairment in functioning and that would not interfere with study participation, be exacerbated by study participation, or introduce scientific difficulties, for example, history of complicated bereavement or history of time-limited alcohol abuse that does not represent a lasting substance use disorder
  • Additional criteria for participants with MDD: Meet DSM-IV criteria for MDD (single or recurrent) as determined by a Structured Clinical Interview for DSM-IV (SCID)
  • Additional criteria for depression-prone participants: Does not meet criteria for current MDD, but meets at least one of the following requirements:

    1. Meets DSM-IV criteria for past MDD (single or recurrent) as determined by a SCID interview
    2. Meets DSM-IV criteria for Depressive Disorder Not Otherwise Specified (NOS)
    3. Meets DSM-IV criteria for Dysthymia
    4. Has a Beck Depression Inventory (BDI) score of 14 or higher

Exclusion Criteria:

  • Current use of any anti-depressant or psychotropic medication while participating in Visits 1-6 and Home Saliva Collection; treatment with electroconvulsive therapy (ECT) within the past 3 months; use of any anti-depressant within 14 days of participation, fluoxetine within 30 days of participation, or any other psychotropic drug within a timeframe based on the half-life of the particular drug
  • Using hormonal contraceptives while participating in Visits 1-6 and Home Saliva Collection
  • Using any medication that affects central nervous system (CNS) function for 2-4 weeks prior to testing and during participation in Visits 1-6 and Home Saliva Collection
  • Using any illicit drug for 4 weeks prior to testing and during participation in Visits 1-6 and Home Saliva Collection
  • Using any steroid, anti-histamine, nasal spray (which includes corticosteroids), or topical hydrocortisone cream/gel that affects the hypothalamic-pituitary-adrenal (HPA) axis for 2-4 weeks prior to testing and throughout the duration of the study
  • History of seizures, diabetes, hypertension, neurological problems, and/or cardiac problems
  • Metallic implants (i.e., prostheses, shrapnel, or aneurysm clips) or electronic implants (i.e., cardiac pacemakers) that are contraindicated for MRI
  • Any clinically significant abnormalities on medical history or physical exam
  • Currently pregnant, trying to become pregnant, breastfeeding, within a six-month window following pregnancy or breastfeeding, sexually active without an acceptable method of birth control (e.g., abstinence, male vasectomy, female sterilization, condom)
  • Post-menopausal and peri-menopausal women
  • Women with highly irregular menstrual cycles (e.g., more than 60 days between periods or less than 14 days between periods)
  • Individuals who work the "night shift" (e.g., between the hours of 11 pm and 7 am) will be excluded due to potential variability in cortisol levels determined by sleep schedule
  • Heavy nicotine user (e.g., smokes more than a pack/day)
  • Unable to fit comfortably in the MRI simulator and/or scanner (e.g., BMI greater than approx. 38)
  • Weight greater than approx. 250 lbs
  • Lifetime history of mania or psychosis
  • At risk for suicide as determined by a clinical interview
  • Gross impairment in functioning
  • Claustrophobia
  • Frank Axis I or Axis II psychopathology that would interfere with study participation, become exacerbated by study participation, or introduce scientific difficulties

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03195933


Sponsors and Collaborators
University of Wisconsin, Madison
National Institute of Mental Health (NIMH)
Brain & Behavior Research Foundation
Investigators
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Principal Investigator: Heather C. Abercrombie, Ph.D. University of Wisconsin School of Medicine & Public Health

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT03195933     History of Changes
Other Study ID Numbers: 2011-0897
R01MH094478 ( U.S. NIH Grant/Contract )
First Posted: June 22, 2017    Key Record Dates
Last Update Posted: June 22, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: We will make our data publicly available on a password protected website after the data are collected and analyzed, and manuscripts presenting data testing our hypotheses are accepted for publication. These data will be thoroughly de-identified. Several classes of data will be made available, including self-report, behavioral, diagnostic, hormonal, and summary data from our physiological and imaging datasets.

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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
Keywords provided by University of Wisconsin, Madison:
Depression
Childhood Adversity
Childhood Abuse
Cortisol
Emotional Memory
Magnetic Resonance Imaging (MRI)
Additional relevant MeSH terms:
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Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Anti-Inflammatory Agents