• INCLUSION CRITERIA:

CRITERIA FOR INCLUSION OF DEPRESSED PATIENTS:

• age 18-65 years
• written informed consent completed (consent-incapacitated subjects will not be eligible)
• score 20 or higher on the Montgomery-Asberg Depression Rating Scale (MADRS)
• meets DSM-IV criteria for chronic or recurrent nonpsychotic MDD
• patients who are on non-excluded concomitant medications.
• no more than 3 failed antidepressant treatments within the current major depressive episode
• no alcohol use (last 7 days)

CRITERIA FOR INCLUSION OF HEALTHY CONTROL SUBJECTS:

• age 18-65 years
• written informed consent completed
• no current or past diagnosis of axis I psychiatric disorder (DSM-IVTR)
• no alcohol use (last 7 days)
• physically healthy

EXCLUSION CRITERIA:

CRITERIA FOR EXCLUSION OF DEPRESSED PATIENTS:

• history of bipolar disorder (I, II, or NOS) (lifetime)
• history of schizophrenia
• history of schizoaffective disorder or
• psychosis NOS (lifetime)
• history of anorexia nervosa or bulimia nervosa (lifetime)
• current primary obsessive-compulsive disorder (OCD)
• history of clear-cut intolerability to the study medication
• lack of response to an adequate trial of the study medication (citalopram) in the current or past episodes of MDD
• did not respond to 7 or more sessions of ECT in the current episode of MDD
• Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
• has general medical condition which contraindicates the use of the study medication
• is on concomitant medication which contraindicates the use of the study medication
• requires immediate hospitalization for psychiatric disorder
• requires antipsychotic medications or mood stabilizers
• Non-postmenopausal (less than 2 years since last period) females of childbearing potential who are sexually active and who are not using adequate (hormonal, double barrier, surgical) contraception, or who are pregnant or breast feeding
• patients currently taking any of the exclusionary medications detailed in protocol (including antipsychotic medications, anticonvulsant medications, antidepressant medications, mood stabilizers, central nervous system stimulants) in the 2 weeks prior to Study Period II.
• patients taking thyroid medication for hypothyroidism may be included if they have been stable on the medication for greater than 3 months
• patients can participate in a modality of psychotherapy that is not targeting the symptoms of depression (e.g., supportive therapy, marital therapy)
• therapy that is depression specific, such as Cognitive Therapy (CT) or Interpersonal Psychotherapy of Depression (IPT) is not allowed during participation
• subjects must be fluent in English and have the capacity to understand the nature of the study and sign the written informed consent.
• current alcohol dependence or abuse (last 3 months)

CRITERIA FOR EXCLUSION OF HEALTHY CONTROL SUBJECTS:

• subjects currently taking any of the exclusionary medications detailed in protocol in the 2 weeks prior to evaluation
• current alcohol dependence or abuse (last 3 months)
• history of major depression or bipolar disorder in any first degree relative