Neurobiology of Treatment Responses in MDD

• Meet DSM V criteria for Major Depressive Episode, single episode or recurrent, for at least a month;
• Unmedicated for at least 10 half-lives of the previous AD used;
• Willing to limit the introduction of any new treatments during the study;
• 18 - 55 years of age;
• Right handed;
• Capable of giving written informed consent;
• Hamilton Depression Rating Scale (17-item HDRS, not including atypical features) >15 at screening and randomization;

Exclusion Criteria:

• Major medical illness (e.g., cancer, HIV, Hepatitis C, etc.) or concurrent, untreated, or symptomatic medical illnesses, including acute or ongoing pain, autoimmune or inflammatory disease;
• Use of narcotic analgesics within the last 6 months or regular use of sleeping aids (including benzodiazepines and related compounds), more than twice a week;
• Recent history of substance abuse (within the last 6 months) or history of substance dependence (lifetime);
• Other comorbid psychiatric illnesses, such as Bipolar Disorder, Obsessive Compulsive Disorder, Panic Disorder, any psychosis, or Axis II diagnoses. Generalized Anxiety and Social Anxiety Disorders will NOT be considered exclusionary given their common association with MDD
• Concurrent participation in other therapeutic trials;
• Pregnancy/nursing;
• Ongoing treatment with medications with psychotropic properties;
• Contraindications to PET or MRI methods;
• Impairments, activities or situations that would prevent completion of the study protocol;
• Prior non-response to duloxetine;
• Active suicidal ideation.
• Urine screens positive for opioids or any substances of abuse.
• Allergy to fentanyl (because of structural similarity to the radiotracer [11C]carfentanil to be employed in the study).