Patient description: A 46-year-old Asian woman with MDD complains of persistent feelings of sadness and loss of interest in daily activities. She states that her mood is still depressed most of the days. She complains of loss of energy and feelings of worthlessness nearly every day. She is on anti-depressants for the past 6 months, but the symptoms are still present. She does not drink alcohol or smoke. She used to exercise every day for at least 30 min., but she doesn't have enough energy to do so for the past 3 weeks. She also has some digestive issues recently. She is married and has 4 children. She is menopausal. Her husband was diagnosed with colon cancer a year ago and is undergoing chemotherapy. Her past medical history is unremarkable. Her family history is negative for any psychologic problems. Her HAM-D score is 20.

Clinical trial eligibility criteria: eligible ages (years): 18.0-50.0,  Major Depression Treatment GROUP: 1. Age 18-50 2. DSM-IV 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  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. GROUP: 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 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