An Investigation of Early Life Stress and Depression
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|ClinicalTrials.gov Identifier: NCT01701258|
Recruitment Status : Recruiting
First Posted : October 5, 2012
Last Update Posted : December 29, 2016
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 or disease||Intervention/treatment||Phase|
|Major Depressive Disorder (MDD) History of Childhood Sexual Abuse (CSA)||Drug: Amisulpride Drug: Placebo||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||92 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Primary Purpose:||Basic Science|
|Official Title:||Early Life Stress and Depression: Molecular and Functional Imaging Approaches|
|Study Start Date :||November 2012|
|Estimated Primary Completion Date :||March 2017|
|Estimated Study Completion Date :||March 2017|
Active Comparator: Amisulpride
single low-dose pharmacological challenge, 50 mg amisulpride tablet
single low-dose pharmacological challenge, 50 mg amisulpride
Other Name: Solian
Placebo Comparator: Placebo
single-dose placebo tablet
single-dose placebo capsule
- Event-related potentials (ERPs) [ Time Frame: ERPs are measured for 30 minutes during session 2 ]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 ]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 ]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 ]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 ]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 ]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 ]Utilizing 11C-altropane during positron emission tomography (PET) scanning allows us to measure dopamine transporter levels.
- 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 ]Self-report questionnaires are administered at all sessions.
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): NCT01701258
|Contact: Rachel Cleggemail@example.com|
|United States, Massachusetts|
|Belmont, Massachusetts, United States, 02478|
|Contact: Rachel Clegg 617-855-4236 firstname.lastname@example.org|
|Principal Investigator: Diego Pizzagalli, PhD|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Georges El Fakhri, PhD 617-726-9640 email@example.com|
|Principal Investigator: Georges El Fakhri, PhD|
|Principal Investigator:||Diego Pizzagalli, PhD||Mclean Hospital|