An Investigation of Early Life Stress and Depression
Condition: Major Depressive Disorder (MDD); History of Childhood Sexual Abuse (CSA)
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major; Stress, Psychological
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to investigate brain pathways within adult females (with a
      history of CSA that occurred between the ages of 5-14) with and without a current diagnosis
      of major depressive disorder (MDD).

      Hypotheses:

      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.
    

Detailed description: 
      This study will include four sessions:

      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.
    

Intervention name(s): Amisulpride; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): single low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only; single-dose placebo capsule during the fMRI session only
Other intervention name(s): Solian
Intervention MeSH terms: Amisulpride
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: There were four groups of subjects: those with a history of child sexual abuse that are currently experiencing a major depressive episode, those with a history of child sexual abuse without a current or past diagnosis of major depressive disorder, those without a history of child sexual abuse that are currently experiencing a major depressive episode, and those with without a history of child sexual abuse and without a current or past diagnosis of major depressive disorder. Within each group, half of the subjects were assigned to receive the study drug (amisulpride) and half to receive a placebo for the fMRI session (session 2 or 3).
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: Depression; Childhood Sexual Abuse; Dopamine; MRI; PET; ERP; Stress; Reward; Childhood trauma; Amisulpride