This study may help identify how abnormalities in brain systems that control the ability to ignore irrelevant information may contribute to the development of depression in older adults.

Approximately half of those who develop depression in late life never had depression before. The classic view is that changes taking place in our brains as we age contribute to the development of late-onset depression. This view is supported by the relative absence of family history for those with late onset depression. This research study will recruit 70 older adults with late life depression and 70 older adults without depression. All participants will receive a sub-clinical, non-contrast (magnetic resonance imaging (MRI) scan at the beginning of the study and then again 12 weeks later at the completion of the study. The depressed older participants will also receive a Food and Drug Administration (FDA)-approved antidepressant, escitalopram (Lexapro), as treatment for their depressive symptoms over 12 weeks. This MRI study may help the researchers identify how abnormalities in brain systems that control our ability to ignore distractions, control our emotions, and anticipate reward may contribute to the development of depression in older adults. The investigators hope that the findings promote the development of tests that may improve the detection of older adults at risk for poor treatment outcomes and eventually guide the development of novel treatments for depression.

Inclusion Criteria:

• Age: 60-85 years, right-handed;
• Diagnosis: Major depression, unipolar (by Structured Clinical Interview for Diagnostic and Statistical Manual (DSM)IV (SCID-R) and DSM-IV criteria);
• Age of onset of first episode ≥ 50 years with up to three depressive episodes;
• Severity of depression: A 24-Item Hamilton Depression Rating Scale (HDRS) ≥ 20.

Exclusion Criteria:

• Psychotic depression by DSM-IV, i.e., presence of delusions with a SCID-R score higher than 2;
• High suicide risk, i.e. intent or plan to attempt suicide in near future;
• Presence of any Axis I psychiatric disorder (other than unipolar major depression) or substance abuse;
• History of psychiatric disorders other than unipolar major depression or generalized anxiety disorder (bipolar disorder, hypomania, and dysthymia are exclusion criteria);
• Dementia: Diagnosis of dementia by DSM-IV;
• Mild Cognitive Impairment (MCI);
• Acute or severe medical illness, i.e., delirium, metastatic cancer, decompensated cardiac, liver or kidney failure, major surgery, stroke or myocardial infarction during the three months prior to entry; or use of drugs known to cause depression, e.g., reserpine, alpha-methyl-dopa, steroids, sympathomimetics withdrawal;
• Neurological brain disease and/or history of electroconvulsive therapy;
• History of any use of citalopram or escitalopram during the current episode or need for drugs that may interact with these agents, i.e. drug metabolized by the 2D6 P450 isoenzyme system;
• Current involvement in psychotherapy;
• Contraindications to MRI scanning including cardiac pacemaker, metallic objects and metallic implants contraindicating MRI, cardiac stent, claustrophobia;
• Inability to speak English;
• Corrected visual acuity < 20/70; Color blindness.

Baseline (Study Entry) through 12 Weeks of Treatment/Participation