An Investigation of Early Life Stress and Depression

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Mclean Hospital
Sponsor:
Collaborators:
Massachusetts General Hospital
Information provided by (Responsible Party):
Diego A. Pizzagalli, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT01701258
First received: October 2, 2012
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

Severe childhood adversity, including childhood sexual abuse (CSA) explains 32-44% of psychiatric disorders and is associated with substantially increased risks for depression and substance abuse later in life. However, 20-40% of adults with a history of CSA report little to no consequences. The neurobiological underpinnings associated with adaptive (resilience) and maladaptive consequences of CSA remain largely unknown. The goal of this study is to investigate brain pathways within adult females (with a history of CSA that occurred between the ages of 5-9) with and without a current diagnosis of major depressive disorder (MDD). We hypothesize that the CSA/MDD participants will be characterized by (1) reduced reward responsiveness and prefrontal cortex activity, but increased cortisol levels, (2) reduced dopamine activity, and (3) reduced dopamine transporter binding. The over-arching purpose of the study is to (1) identify individuals at risk for psychopathology and maladaptive behavior, (2) prevent re-victimization, and (3) develop more targeted therapeutic interventions.

This study involves 4 sessions, described below.

Session 1 (SCID Session) The first session takes place at the Center for Depression, Anxiety, and Stress Research (CDASR) or Neuroimaging Center (both at McLean Hospital) and involves consenting, a clinical evaluation, a series of questionnaires, and a medical assessment.

Session 2 or 3 (fMRI Session) The third session takes place at the Neuroimaging Center. Using a double-blind design, participants will be administered either amisulpride (50 mg) or placebo. Participants will complete the Monetary Incentive Delay (MID) task during functional magnetic resonance imaging (fMRI) and the Probabilistic Stimulus Selection Task (PSST) afterwards.

Session 2 or 3 (PET Session) This session takes place at Massachusetts General Hospital. 9 mCi of [11C] altropane will be injected by a trained nuclear medicine technician and positron emission tomography (PET) scanning will begin. Prior to the PET scan, a blood serum pregnancy test will be administered for females.

Session 4 (ERP Session) The fourth session takes place at the CDASR and involves an electroencephalography (EEG) recording, the Probabilistic Reward Task (PRT), and collecting saliva samples to assess cortisol levels.


Condition Intervention
Major Depressive Disorder (MDD)
History of Childhood Sexual Abuse (CSA)
Drug: Amisulpride
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: Early Life Stress and Depression: Molecular and Functional Imaging Approaches

Resource links provided by NLM:


Further study details as provided by Mclean Hospital:

Primary Outcome Measures:
  • Event-related potentials (ERPs) [ Time Frame: ERPs are measured for 30 minutes during session 2 ] [ Designated as safety issue: No ]
    ERPs are a measure of brain activity and are measured while participants perform the Probabilistic Reward Task (PRT)

  • Behavioral Performance in Probabilistic Reward Task (PRT) [ Time Frame: 20 minute task administered during session 2 ] [ Designated as safety issue: No ]
    The Probabilistic Reward Task (PRT) operationalizes reward sensitivity and reward learning.

  • Cortisol levels [ Time Frame: Saliva samples for cortisol analysis are collected at 3 points during session 2: 20 minutes after subject arrival, 20 minutes after stress exposure, and 60 minutes after stress exposure ] [ Designated as safety issue: No ]
    Participants are exposed to stress, in the form of negative performance feedback, during session 2. Saliva is collected before and following stress exposure. Cortisol levels are measured giving a correlate of stress response.

  • Brain activity and structure (MRI Data) [ Time Frame: MRI scans totaling 90 minutes take place during session 3 ] [ Designated as safety issue: No ]
    Brain activity and structure is measured using various MRI techniques, including fMRI, DTI, and structural scans. Participants perform the Monetary Incentive Delay (MID) task during the fMRI. Resting-state fMRI data are also collected.

  • Behavioral Performance in Monetary Incentive Delay (MID) task [ Time Frame: 30 minute task administered during session 3 ] [ Designated as safety issue: No ]
    The MID task is designed to identify brain activity specific to anticipation or consumption of incentives.

  • Behavioral performance in the Probabilistic Stimulus Selection Task (PSST) [ Time Frame: 45 minute task administered during session 3 ] [ Designated as safety issue: No ]
    The PSST examines whether participants exhibit a bias for choosing frequently reinforced or avoiding frequently punished stimuli, and thus to assess positive and negative reinforcement learning.

  • Dopamine Transporter Levels [ Time Frame: 1 hour PET scan during session 4 ] [ Designated as safety issue: No ]
    Utilizing 11C-altropane during positron emission tomography (PET) scanning allows us to measure dopamine transporter levels.


Secondary Outcome Measures:
  • Ratings of Mood and Affect [ Time Frame: Self-report measures are administered at all 4 sessions which take place within an average of 3 weeks ] [ Designated as safety issue: No ]
    Self-report questionnaires are administered at all sessions.


Estimated Enrollment: 92
Study Start Date: November 2012
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Amisulpride
single low-dose pharmacological challenge, 50 mg amisulpride tablet
Drug: Amisulpride
single low-dose pharmacological challenge, 50 mg amisulpride
Other Name: Solian
Placebo Comparator: Placebo
single-dose placebo tablet
Drug: Placebo
single-dose placebo capsule
Other Name: placebo

  Eligibility

Ages Eligible for Study:   20 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

General Inclusion Criteria:

  • Females of all ethnic origins, age between 20 and 45; right-handed (Chapman & Chapman 1987);
  • 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 for Childhood Sexual Abuse/MDD (CSA/MDD) Group:

  • At least three incidents of contact sexual abuse1 between the ages 5-9 years;
  • No incidents of verbal or other abuse (ascertained using the Traumatic Antecedents Questionnaire);
  • Current DSM-IV diagnostic criteria for MDD (as diagnosed with the use of the SCID);

Inclusion Criteria for Childhood Sexual Abuse/Resilient (CSA/RES) Group:

  • At least three incidents of contact sexual abuse1 between the ages 5-9 years;
  • No incidents of verbal or other abuse (ascertained using the Traumatic Antecedents Questionnaire);
  • Absence of past or current DSM diagnosis, including MDD or alcohol/substance abuse;

Inclusion Criteria for Non-traumatized, MDD (MDD) Group:

  • No incidents of sexual, verbal, or physical abuse (ascertained using the Traumatic Antecedents Questionnaire);
  • Current DSM-IV diagnostic criteria for MDD (as diagnosed with the use of SCID);

Non-traumatized, healthy controls (controls):

  • No incidents of sexual, verbal, or physical abuse (ascertained using the Traumatic Antecedents Questionnaire);
  • Absence of any medical, neurological, and psychiatric illness (including alcohol/substance abuse) For the CSA/MDD and CSA/RES groups, concurrent physical abuse will be allowed if it (1) involved abuse below the shoulders (to minimize risk of traumatic brain injury) and (2) temporally overlapped with CSA.

Exclusion Criteria:

  • Participants with suicidal ideation where study participation is deemed unsafe by the study clinician;
  • Pregnant women or women of childbearing potential who are not compliant with the requirements of a urine and blood pregnancy test.
  • Failure to meet MRI or PET safety requirements.
  • Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine (hypothyroidism), neurologic or hematologic disease;
  • Past/current DSM diagnosis of: PTSD, OCD, ADHD, schizophrenia, schizoaffective disorder, delusional disorder, bipolar disorder, mood congruent/incongruent psychotic features, substance dependence, substance abuse within the last 12 months (with the exception of cocaine or stimulant abuse, which will lead to automatic exclusion);
  • Simple phobia, social anxiety disorder and generalized anxiety disorders will be allowed only if secondary to MDD and only in the CSA/MDD and MDD groups (which will be matched for comorbidities);
  • History of seizure disorder; renal insufficiency; history of adverse reactions to amisulpride;
  • History of cocaine, stimulant, and other DA drug use [e.g., (meth)amphetamine), methylphenidate].
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01701258

Contacts
Contact: Franziska Goer 617-855-4236 fgoer@mclean.harvard.edu

Locations
United States, Massachusetts
McLean Hospital Recruiting
Belmont, Massachusetts, United States, 02478
Contact: Andrew Cohen    617-855-4237    acohen@mclean.harvard.edu   
Principal Investigator: Diego Pizzagalli, PhD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Georges El Fakhri, PhD    617-726-9640    elfakhri@pet.mgh.harvard.edu   
Principal Investigator: Georges El Fakhri, PhD         
Sponsors and Collaborators
Mclean Hospital
Massachusetts General Hospital
Investigators
Principal Investigator: Diego Pizzagalli, PhD Mclean Hospital
  More Information

No publications provided

Responsible Party: Diego A. Pizzagalli, Associate Professor of Psychiatry, Harvard Medical School, Mclean Hospital
ClinicalTrials.gov Identifier: NCT01701258     History of Changes
Other Study ID Numbers: 2012P002593, 5R01MH095809
Study First Received: October 2, 2012
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Mclean Hospital:
Depression
Childhood Sexual Abuse
Dopamine
MRI
PET
ERP
Stress
Reward

Additional relevant MeSH terms:
Depression
Depressive Disorder
Stress, Psychological
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Sultopride
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014