To determine the psychobehavioral and neurohormonal mechanisms of effective treatment, we will conduct a randomized, double-blind, placebo-controlled trial in patients with major depression, who will receive either: (i) computer-based cognitive behavioral therapy (CBT) program entitled “Beating the Blues” + placebo, or (ii) computer-based cognitive behavioral therapy (CBT) program entitled “Beating the Blues” + the SSRI antidepressant escitalopram. We will assess (a) glycemic control (levels of HbA1c), in relation to (b) adherence (keeping scheduled return appointments, diet, exercise, and glucose monitoring), (c) depressive symptoms (neurocognitive and neurobehavioral symptoms determined by self- and observer-rated scales), and (d) the four pathways of neurometabolic function.

Study visits will occur once a month for 6 months. Should patients report severe environmental stressors (such as marital conflict, loss of family member or job, being exposed to trauma), patients will be offered an intensification of their contact with study personnel, e.g. weekly contact by phone or “in-person” visits to see study personnel at the Grady Diabetes Clinic.

After completion of 6 months, patients may enter an open-label treatment with escitalopram or be tapered off their study medication. If patients develop worsening depressed mood, at any time during the study they will be offered treatment with open-label escitalopram or an alternative antidepressant for the remainder of the 52 weeks of the study.

Inclusion Criteria:

• Subjects must be English-speaking

• African American

• Have type 2 diabetes per American Diabetes Association criteria

• Patient’s receiving care at Grady Hospital

Exclusion Criteria:

• Severely depressed (Hamilton Depression Rating Scale (HAM-D) ≥ 34

• Non - English speaking

• Women who are pregnant, women who will be breastfeeding during the study, and women of childbearing potential who are not practicing a reliable method of birth control.

• currently meet DSM-IV criteria for:

• Bipolar Disorder

• Schizophrenia or any Psychotic Disorder

• Obsessive Compulsive Disorder

• Mental Retardation or any Pervasive Developmental Disorder or Cognitive Disorder.

• Personality Disorder of sufficient severity to interfere with their participation in the study

• Psychotic features or with history of Psychotic Disorder, as defined by DSM-IV

• Suicide risk, or have made serious suicide attempt in the past year

• Substance Abuse or Dependence (other than nicotine) during the six months preceding the first dose of double blind study medication

• Any malignancy (other than excised basal cell carcinoma), or any clinically significant hematological, endocrine, cardiovascular (including any rhythm disorder), renal, hepatic, gastrointestinal, or neurological disease. History of syndrome of inappropriate anti-diuretic hormone secretion.

• Diabetes due to: glucagonoma, pheochromocytoma or other endocrine neoplasm, drug induced diabetes, gestational diabetes, or those with established genetic defects of beta cell function.

• Medical conditions that will interfere with the HbA1c assay or if hospitalization is likely within two months (sickle cell anemia, hypersplenism)

• A history of diabetic ketoacidosis episode during the 6 months preceding the first dose of double-blind study medication.

• Uncontrolled diabetes as judged by the investigator defined as blood glucose greater than 400 on last two visits or patients whom suffered from diabetic ketoacidosis in the last month or have had 2 episodes in the last year.

• Autonomic or peripheral neuropathy that requires treatment

• At the first follow-up visit - Patients with systolic blood pressure greater than 180 mm Hg or less than 90 mm Hg or diastolic blood pressure greater than 105 mm Hg or less than 50 mm Hg

• Treatment with a depot neuroleptic during the last 6 months

• Patients who have been treated with any neuroleptic, antidepressant, or anxiolytic medication OR ANY OF THE MEDS BELOW during in the last 2 weeks (8 weeks for fluoxetine)

  1-(Aminomethyl)cyclohexaneacetic acid 5-Hydroxytryptamine Alprazolam Amitriptyline-doses greater than 50 mg/day Amoxapine-doses greater than 50 mg/day Aripiprazole Atomoxetine Beconase Benadryl Benztropine mesylate Bupropion Carbamazepine Citalopram Clozapine Coumadin Desipramine-doses greater than 50 mg/day Dextroamphetamine Escitalopram Felbamate Fluoxetine Flurazepam Guanethidine Guanethidine Haloperidol Hydrocortisone Imipramine-doses greater than 50 mg/day Isosorbide dinitrate Kava kava Lamotrigine Lithium Lorazepam Maprotiline-doses greater than 50 mg/day Methyldopa Methylphenidate Mifepristone Mirtazapine Modafinil Nefazodone Nitroglycerin Nitroprusside Nortriptyline-doses greater than 50 mg/day Olanzapine Paroxetine Pemoline Phenelzine Phenylephrine Phenylpropanolamine Pramipexole Prednisone Reserpine Risperidone S-adenosyl-methionine (SAME) Sinequan-doses greater than 50 mg/day St. John’s Wort Tempazepam Testosterone injections or patches Tetrahydrozoline Theophylline Tranylcypromine Trazodone Valerian Root Valproic acid Warfarin Zalpelon Ziprasidone Zonisamide Zolpidem

• Participation in an investigational drug study within 1 month prior to study entry or who have received treatment with an investigational drug within 1 month or five half-lives, whichever is longer.

• Previous investigational study of escitalopram or previously treated with escitalopram in a dose and duration sufficient for therapeutic trial.

• History of hypersensitivity reaction to escitalopram or citalopram.

• Electroconvulsive therapy during the past 3 months

• Initiation or termination of behavior therapy or psychotherapy in the 3 months.

• Positive urine screening for alcohol, illicit drugs, or any prohibited medication