Depression and Dopamine Transporter Function Study Using C-11 Altropane

Criteria for All Subjects

Inclusion Criteria:

1. Written informed consent;

2. Both genders and all ethnic origins, age between 18 and 45;

3. Right-handed (Chapman and Chapman 1987);

4. Absence of any medications for at least 3 weeks;

5. Absence of pregnancy;

6. Absence of current drug use (cocaine, cannabinoids, opiates, amphetamines,
benzodiazepines and barbiturates) as assessed by urinary drug test.

7. For women, completion of a negative urine pregnancy test prior to the MRI scan, as
well as a negative STAT quantitative serum hCG test immediately prior to
radiopharmaceutical exposure;

8. Normal or corrected-to-normal vision and hearing.

Exclusion Criteria

1. Pregnant or currently breast-feeding women or any woman of childbearing potential who
is seeking to become pregnant or suspects that she may be pregnant.

2. History or current serious or unstable medical illness, including cancer,
cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic
disease;

3. History of seizure disorder;

4. Failure to meet standard PET safety requirements;

5. Failure to meet standard fMRI safety requirements;

6. Students and employees supervised by the Investigators at MGH, McLean Hospital and
Harvard University;

7. Absence of fluency in written and spoken English;

8. History of head injury;

9. History or current use of cocaine, stimulants, or other dopaminergic drugs.

10. Diabetes with poor glucose control;

11. History or current diagnosis of dementia, or a score of < 26 on the Mini Mental Status
Examination (Folstein, 1975) at the screening visit;

12. Clinical or laboratory evidence of hypothyroidism or currently taking thyroid
medication;

13. Currently taking medication that affects blood flow, e.g. certain blood pressure
medications

14. Evidence of significant inconsistencies in self-report.

Criteria Specific to MDD subjects

Inclusion Criteria:

1. DSM-IV diagnostic criteria for MDD (diagnosed with the use of the SCID);

2. A baseline HRSD score (Hamilton 1960) greater than or equal to 16 (17-item version);

Exclusion Criteria:

1. Subjects with suicidal ideation where outpatient treatment is determined unsafe by the
study clinician. These patients will be immediately referred to appropriate clinical
treatment;

2. History or current diagnosis of: learning and developmental disorders (including ADHD
and autism spectrum disorders), anorexia nervosa, cognitive disorders, somatoform and
factitious disorders, dissociative disorders, personality disorders, organic mental
disorders, schizophrenia or other psychotic disorder, bipolar disorder, obsessive
compulsive disorder; simple phobia, social anxiety disorder and generalized anxiety
disorder are allowed if secondary to MDD.

3. History of substance dependence lifetime or substance abuse within the last 12 months;

4. History of bulimia nervosa or PTSD within the past 2 years;

5. History or current diagnosis of dementia, or a score of < 26 on the Mini Mental Status
Examination (Folstein, 1975) at the screening visit;

6. Current use of other psychotropic drugs;

7. Patients with lifetime electroconvulsive therapy (ECT);

8. Presence of any psychotropic medications for at least 2 weeks:

- 6 months for dopaminergic drugs (including methylphenidate),

- 6 weeks for fluoxetine,

- 6 months for neuroleptics,

- 2 weeks for benzodiazepines,

- 2 weeks for any other antidepressants.

Criteria Specific to Control subjects

Inclusion Criteria:

1. Absence of medical, neurological, and psychiatric illness (including alcohol and
substance abuse), as assessed by subject history and a structured clinical interview
(SCID-I/NP);

2. Absence of any medications for at least 3 weeks;

Exclusion Criteria:

1. History or current diagnosis of any of DSM-IV psychiatric illness;

2. First degree relative with mood disorder or psychosis;

3. History or current use of any psychiatric medication.