This study will evaluate changes in brain gamma-aminobutyric acid (GABA) levels due to treatment with escitalopram in people with major depressive disorder.

Major depressive disorder (MDD) is a severe form of depression. MDD can significantly interfere with an individual's thoughts, behavior, mood, and physical health. People who suffer from MDD often experience feelings of worthlessness; they may feel hopeless and may be unable to cope with problems in their life. In addition, they often experience sleep disruption, loss of appetite, and chronic pain.

The purpose of the study is to compare images taken of the brains of people who are depressed and the brains of healthy volunteers. Specifically, we want to see if symptoms of depression are related to a decrease in a brain chemical called GABA. We measure the concentration of GABA using a brain-scanning device called "magnetic resonance spectroscopy" (or "MRS"), which is a type of MRI.

The study lasts for 14 weeks and involves 8 visits to our MGH clinic in Boston. The first visit is the screening visit, which can last up to 3 hours. The rest of the visits are about a half hour long and take place every other week. In addition to these 8 visits, there are also 2 visits to McLean Hospital Brain Imaging Center for the MRS scans. The first scan takes place within a few days after the screening visit, and the second scan will be at the end of the 14 weeks. Each scan visit lasts between an hour and a half and two hours. Subjects are reimbursed $50 per MRS scan and $25 per visit to McLean to cover travel costs.

All subjects in this study will receive escitalopram (or Lexapro), which is an antidepressant medication approved by the Food and Drug Administration. Subjects start at 10 mg daily of the escitalopram, but may be increased up to 30 mg if the study doctor thinks it is appropriate.

Inclusion Criteria:

• Meet diagnostic criteria for current Major Depressive Disorder
• Men or women aged 18-65
• Medication-free for one week prior to the start of the study
• Agrees to use an effective form of contraception throughout the study

Exclusion Criteria:

• Anyone who is suicidal
• Pregnant or breastfeeding women
• Anyone with a serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
• Anyone with a history of seizure disorder or hypothyroidism
• Anyone with a history of psychiatric disorders including bipolar disorder, schizophrenia, psychoses, or substance abuse (including alcohol abuse active within the last 12 months)
• Anyone with a history of intolerance or multiple adverse drug reactions or allergy to (es)citalopram.
• Patients who are currently taking medications active on GABA, including benzodiazepines.

Adverse events were collected over 12 weeks of treatment.