fMRI Study of Treatment Changes in Major Depression

The overall purposes of this research are to determine if Cognitive Behavioral Therapy (CBT)
has the same healing effect on the brain for people with depression as traditional
antidepressants do, to find out more about the causes of depression and why people differ in
the extent of problems caused by depression, and to determine if certain differences in genes
within populations are related to clinical symptoms.Genes we are examining for this study are
COMT, BDNF, and 5-HTT long arm and short arm, as well as future genes that may be discovered
to play a role in depression at a later time, and will be determined by examining saliva and
blood samples. We are primarily studying depression by functional Magnetic Resonance Imaging
(fMRI) which allows us to identify certain parts of the brain that show how the brain works
in controlling negative feelings. Participants will be imaged while performing different
tasks that are believed to activate emotional circuitry of the brain. Comparisons of
activation patterns across these tasks will be used to characterize the cognitive mechanisms
supported by different cortical regions, and to determine patterns of functional brain
deficits in subjects with depression. Comparisons will also be made between changes that
occur after treatment with an approved antidepressant and treatment with CBT.

DEPRESSED GROUP:

Inclusion criteria:

1. Age 18-50

2. DSM-IV criteria for major depressive disorder (MDD)

3. Minimum Hamilton Rating Scale for Depression (HAMD) score > 18

4. Right handed

5. Capacity to give informed consent and follow study procedures

6. English speaking

Exclusion criteria:

1. Cannot give informed consent

2. Significant handicaps (e.g. visual or hearing loss, mental retardation) that would
interfere with testing procedures

3. Does not speak English

4. Known primary neurological disorders

5. Any other factor that in the investigators judgment may affect patient safety or
compliance (e.g. distance greater than 100 miles from clinic)

6. MRI contraindications e.g. foreign metallic implants, pacemaker

7. Known allergy or hypersensitivity to sertraline

8. Active suicidality

9. Severe or unstable medical illness or conditions or drugs that may cause depression

10. Any of the following diagnosed by DSM-IV: alcohol or substance abuse disorder,
schizophrenia or other psychotic disorder, bipolar disorder, psychotic features of
depression, current obsessive compulsive disorder (OCD) or panic disorder. In general,
subjects with a history of other Axis I disorders prior to their depression will be
excluded.

11. Current episode has failed to respond to adequate trials of two prior antidepressants
for at least 6 weeks at therapeutic doses.

12. Treatment with sertraline for at least one month in past 3 months.

13. Current use of psychotropic prescription or nonprescription drugs or herbals (e.g.
hypericum) except for limited use of certain hypnotics.

14. Current psychotherapy

15. Treatment with psychotropic drugs or drugs that affect the CNS such as beta-blockers
or mood stabilizers.

CONTROL GROUP:

Inclusion criteria:

1. Age 18-50

2. No history of MDD

3. HAMD score < 7

4. Right handed

5. Capacity to give informed consent and follow study procedures

6. English speaking

Exclusion criteria:

1. Cannot give informed consent

2. Significant handicaps (e.g. visual or hearing loss, mental retardation) that would
interfere with testing procedures

3. Does not speak English

4. Known primary neurological disorders

5. Any other factor that in the investigators judgment may affect patient safety or
compliance (e.g. distance greater than 100 miles from clinic)

6. MRI contraindications e.g. foreign metallic implants, pacemaker

7. Severe or unstable medical illness or conditions or drugs that may cause depression

8. Any of the following diagnosed by DSM-IV: alcohol or substance abuse disorder,
schizophrenia or other psychotic disorder, bipolar disorder, major depression, OCD or
panic disorder.

9. Current use of psychotropic prescription or nonprescription drugs or herbals (e.g.
hypericum) except for limited use of certain hypnotics.

10. Treatment with psychotropic drugs or drugs that affect the CNS such as beta-blockers
or mood stabilizers.