This study will examine brain responses associated with reinforcement and reward tasks in individuals with major depressive disorder (MDD).

Major depressive disorder (MDD) is a severe form of depression that can significantly interfere with an individual's thoughts, behavior, mood, and physical health. People who suffer from MDD may experience anhedonia, or the inability to gain pleasure from normally pleasurable experiences. Such individuals do not respond to motivational rewards in the same way as do individuals who are not depressed. Anhedonia has been recognized as a core symptom of depression and it is not always remedied with antidepressant medication. Abnormal brain activity and processing may be the underlying cause of depression and specifically anhedonia. A better understanding of the brain mechanisms of depression may lead to the development of new effective medications or psychological treatments.

Event-related potential (ERP), which measures electrical activity in the brain, and functional magnetic resonance imaging (fMRI), which uses scanned images to illustrate changes in brain activity, are two techniques that can identify abnormal areas of brain processing. The purpose of this study is to use ERP and fMRI to compare brain activity that is related to reward processing in individuals with MDD versus individuals without MDD.

This study will consist of 3 study visits; visits will be scheduled as close together as possible. At the first study visit, potential participants will be assessed with the SCID (Structured Clinical Interview for DSM-IV), which will identify individuals with the diagnostic criteria for MDD. A control group of non-depressed individuals will also be enrolled in the study. During the second and third study visits, participants will take part in a monetary reinforcement reward task followed by a signal detection reward task. Brain activity of all participants will be monitored during both tasks. During the second study visit, ERP will be used; during the third study visit, fMRI will be used. Demographic information will also be collected, and participants will complete several standardized questionnaires to assess mood. Some participants will be asked to return after eight weeks to complete the fMRI and EEG sessions again. Those who do complete all five sessions will be awarded a bonus.

Overall Inclusion Criteria:

• Right-handed
• Agrees to use an effective form of contraception throughout the study

Inclusion Criteria for Depressed Participants:

• Meets overall inclusion criteria
• Meets DSM-IV diagnosis criteria for major depressive disorder
• Score of at least 16 on the 21-item HAM-D scale

Overall Exclusion Criteria:

• Left-handed or ambidextrous
• Claustrophobic
• Neurological or medical illness (e.g., attention deficit hyperactivity disorder, head injury, loss of consciousness, seizures)
• Pregnant

Exclusion Criteria for Depressed Participants:

• Meets any of the overall exclusion criteria
• Has been treated with electroconvulsive therapy within 6 months of study entry
• Has taken any benzodiazepine medications for at least 2 weeks prior to study entry and discontinued use of the medication for reasons other than participating in the study
• Has taken any dopaminergic medications (including methylphenidate) or neuroleptics for at least 6 months prior to study entry and discontinued use of the medication for reasons other than participating in the study
• Has taken any fluoxetine medications for at least 6 weeks prior to study entry and discontinued use of the medication for reasons other than participating in the study
• Has taken any medications that may have antidepressant properties (including some herbal supplements) within 2 weeks of study entry
• Has taken any medications that may affect blood flow (including some blood pressure medications) within 2 weeks of study entry
• Current or past history of MDD with psychotic features
• Meets DSM-IV diagnosis criteria for organic mental disorder; substance use disorder (within 1 year of study entry); lifetime substance dependence; schizophrenia; delusional disorder; bipolar disorder; post-traumatic stress disorder; eating disorder; acute bereavement; severe borderline or antisocial personality disorder; or any psychotic disorder not otherwise specified
• Current primary diagnosis of panic disorder, social phobia, generalized anxiety disorder, obsessive-compulsive disorder, or somatoform disorder

Exclusion Criteria for Control Participants

• Meets any of the overall exclusion criteria
• Diagnosed with any medical or neurological illness
• Diagnosed with any current or past psychiatric illness, as assessed by the SCID-I, including substance abuse or dependence (e.g., alcohol)
• Has taken any medications that may have antidepressant properties (including some herbal supplements) within 2 weeks of study entry
• Has taken any psychotropic medications within 2 weeks of study entry
• Has taken any medications that may affect blood flow (including some blood pressure medications) within 2 weeks of study entry

Exclusion Criteria for fMRI Studies:

• Meets any of the overall exclusion criteria
• Fails to meet safety standards for fMRI
• Current back problems
• Has strongly corrected vision, but does not wear contact lenses
• Weighs more than 250 pounds or exceeds the limit of height-to-weight ratio for a comfortable fit in the scanner
• Pregnant
• Current alcohol or substance abuse
• At risk for suicide or homicide