An Investigation of Early Life Stress and Depression

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.

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].