The proposed work aims to examine the neural changes associated with fast-acting antidepressant treatments in order to develop imaging-based biomarkers of treatment response for depression.

Over the past decade, neuroimaging tools have rapidly advanced the field of neural biomarkers of treatment response in depression. Still, despite obvious scientific progress in this field, the ability to implement neuroimaging biomarkers of antidepressant treatment response in clinical trial settings is lacking. In order to objectively assess the neural bases of treatment response in depression, the investigators will use a "Real-time Neurofeedback fMRI task", specifically designed to record and modulate mood improvement by providing neurofeedback in the context of the administration of an antidepressant treatment. In a pilot study, positive neurofeedback during the administration of the drug was associated with significant acute mood improvement and increased blood oxygen level dependent (BOLD) responses in the rostral anterior cingulate cortex (rACC), a common neural target of antidepressant treatments. The central hypothesis is that antidepressant effects in depression are mediated by increased neural activity in the rACC (AIM1), which can be used in clinical trials of antidepressant treatment to predict antidepressant effects (AIM 2) and assess the effect of antidepressant treatment on antidepressant-induced rACC neural responses (AIM 3). The results obtained from this project are expected to have an important impact on our ability to understand the cognitive and neural mechanisms implicated in antidepressant treatment responses in patients with depression, as well as on the ability to implement neuroimaging biomarkers of treatment response in the clinical trial settings.

Inclusion Criteria:

• A man or woman age of 18 or older.
• Currently experiencing a depressive episode as part of Major Depressive Disorder.
• Able to tolerate lying still on your back for 60 minutes at a time.
• Have had no more than one failed antidepressant trial of adequate dose and duration.
• Have been antidepressant medication-free for at least 21 days prior to collection of imaging data (5 weeks for fluoxetine)

Exclusion Criteria:

• Are currently taking any psychiatric medication, or any potentially augmenting or sedative drugs.
• Have a history of inadequate response/tolerability to escitalopram; or history of resistant depression
• Pregnant or breastfeeding or plan to become pregnant over the duration of the study.
• Have a history (lifetime) of psychotic depressive, schizophrenic, bipolar, schizoaffective, or other Axis I psychotic disorders.
• Meet criteria for substance dependence in the last 6 months, except nicotine, or substance abuse in the last 2 months.
• Have a medical condition that contradicts treatment with escitalopram.
• Are currently receiving psychotherapy or any other treatment for your depression.

The study will follow NIMH schedule for data sharing for clinical trials. The schedule allows for descriptive data to be submitted - but not shared - ongoing and results associated with a finding - both positive and negative - to be submitted prior to the communication of a result. Once a result is communicated, either through publication and/or on the NDCT website the data specifically defined to the clinical trial will then be shared.

Eight weeks.