Inclusion Criteria for Depressed Patients:

• Ages 18 - 60 years and able to give voluntary informed consent.
• Satisfy criteria for Major Depressive Disorder (MDD) and current depressed episode using the Structured Clinical Interview for DSM-IV (SCID-IV).
• 17-item Hamilton Depression Rating Scale (HDRS) score > 18.
• Satisfy criteria to undergo an MRI scan based on MRI screening questionnaire.

• Able to be managed as outpatients for initial assessment and during treatment as ascertained by the following:

  • Symptoms not worsening by more than 10 points on the HDRS during the course of the study.
  • No danger to self or others.

Exclusion criteria for patients:

• Meeting DSM-IV criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, bipolar disorder, atypical psychosis, mental retardation, or organic mental (including organic mood) disorder.
• Known hypersensitivity to duloxetine or any of the inactive ingredients.
• On monoamine oxidase inhibitors in the past 2 weeks.
• History of narrow angle glaucoma
• Lack of response of the current episode of depression to two or more adequate courses of antidepressant therapy at a clinically appropriate dose for a minimum of 4 weeks or, in the judgment of the investigator, the patient meets criteria for treatment-resistant depression.
• Use of neuroleptic in the past 2 weeks.
• Use of antidepressants in the past 2 weeks. If on fluoxetine in the past, then should not have been on this medication for 4 weeks.
• History of lack of response to duloxetine.
• Use of mood stabilizers in the past 2 weeks.
• Use of benzodiazepines in the past 2 weeks.
• Acutely suicidal or homicidal or requiring inpatient treatment.
• Meeting DSM-IV criteria for other substance dependence within the past year, except caffeine or nicotine. The criteria will be evaluated by interview and urinary toxicology screening initially and on test days.
• Use of alcohol in the past 1 week.
• No serious medical or neurological illness as assessed by physical examination and laboratory examination including CBC and blood chemistry.
• Current pregnancy or breast-feeding.
• Metallic implants.
• Previously known positive HIV blood test as reported by the subject.