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
Intervention: Amisulpride; Placebo
Intervention description: single low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only; single-dose placebo capsule during the fMRI session only
Intervention MeSH terms: Amisulpride
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
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)
Enrollment: 153.0
Sex: Female
Minimum age: 20 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Depression; Childhood Sexual Abuse; Dopamine; MRI; PET; ERP; Stress; Reward; Childhood trauma; Amisulpride

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.
    

Eligibility 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 one incident of contact sexual abuse1 between the ages 5-14 years;

          -  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 one incident of contact sexual abuse1 between the ages 5-14 years;

          -  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)

        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: 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].