The purpose of this study is to find out what parts of the brain have increased or decreased activity when people are depressed and how antidepressant medicine changes this activity in depressed patients. The genetic samples collected are to look at variation in a gene (serotonin transporter gene), which affects the functioning of the chemical serotonin in the brain

This study will measure the activity in different parts of the brain, while the patients are seeing some pictures, using Magnetic Resonance Imaging (MRI) scan. For this study three MRI scans will be conducted. One before the patient begins on any medication, one during the study after 3 weeks of treatment and one after six more weeks of treatment with a standard antidepressant called duloxetine.

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.

8 weeks

Small numbers of subjects analyzed.