Imaging Serotonin 5HT1A Receptors in Patients With Major Depressive Disorder

* INCLUSION CRITERIA: Patients with MDD (Inclusion criteria): 1. Subjects must be between 18-55 years old. 2. Subjects must be able and willing to give written informed consent. 3. Subjects must have a DSMIV diagnosis of Major Depressive Disorder (MDD). 4. Subjects must at the time of study enrollment be experiencing an episode of Major Depression per DSMIV criteria, and as demonstrated by a Hamilton Depression Rating Scale (HDRS; 17 item) greater than 18 (Williams, 1988). Healthy Volunteers (Inclusion criteria): 1. Subjects must be adults between 18-55 years old. 2. Subjects must be able and willing to give written informed consent. 3. Hamilton Depression Rating Scale (HDRS-17 item) less than 8. EXCLUSION CRITERIA: Patients with MDD (Exclusion criteria): 1. With the exception of substance abuse and anxiety disorders, any past or current Axis I diagnosis other than Major Depressive Disorder. With regard to substance abuse disorders, we will allow past diagnoses so long as there is no question of substance or alcohol dependence, the patient has not had substance abuse patterns in the year prior to enrollment, and other criteria regarding LSD and ecstasy use are met (see below). We will screen for substance abuse patterns in the year prior to enrollment by excluding heavy alcohol use, as defined as greater than 14 drinks per week for men and greater than 7 drinks per week for women. With regard to anxiety disorders, we will allow past or present diagnoses of Generalized Anxiety Disorder, social phobia and panic disorder, so long as the anxiety disorder is not felt to outweigh the magnitude of the diagnosis of Major Depressive Disorder. This will be determined by clinical investigators in this protocol. Particular attention will be made to ensure that the patient does not have a diagnosis of Bipolar disorder, Schizoaffective disorder or Premenstrual dysphoric disorder (PMDD). 2. Any history of Lysergic acid diethylamide (LSD) use, because it may alter serotonin receptor properties. 3. History of ecstasy use more than 3 times in life, because it may alter serotonin receptor properties. 4. Current suicidality or serious depressive symptoms warranting more intensive management than weekly visits in our psychiatric outpatient clinic 5. Psychiatric symptoms warranting psychotropic medications other than the selected SSRI study drug. The exception to this is infrequent use of benzodiazepine (e.g. lorazepam (Ativan), 0.5-1.0 mg for anxiety). Infrequent is defined here as less often than 3 times per week. 6. In women, irregular menses such that it will not be possible to determine the phase of the cycle. This is because previous data show that the phases of the menstrual cycle may affect 5-HT1A binding by radioligand. 7. Clinically significant laboratory abnormalities. 8. Psychotropic medication use (including benzodiazepines and illicit drugs) during the 21 days (42 days for fluoxetine) prior to the PET scan. The exception would be 1-5 doses of 0.5-1.0mg of benzodiazepine (lorazepam (Ativan)) by mouth, separated by at least 24 hours between doses, for anxiety related to study procedures. 9. Serious medical problems including but not limited to chronic neurological disease such as multiple sclerosis, autoimmune diseases, brain masses or lesions \> 1cm in diameter. 10. Positive HIV status. 11. Metallic foreign bodies that would be affected by the MRI magnet, or fear of enclosed spaces likely to make the subject unable to undergo an MRI scan. 12. Head trauma resulting in a period of unconsciousness lasting longer than 10 minutes. 13. History of fetal alcohol syndrome or other neurodevelopmental disorder. 14. Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits. 15. Positive urine drug screen. 16. Inability to lie flat on camera bed for about 2.5 h 17. History of adverse reaction to the medication that we plan to use in the patient, which will be selected among sertraline (Zoloft), citalopram (Celexa) or escitalopram (Lexapro) 18. Pregnancy at time of scan (BetaHCG will be measured in all female patients within 24 hours of scan and must be negative) Healthy Volunteers (Exclusion criteria): 1. With the exception of substance abuse, any past or current Axis I diagnosis. With regard to substance abuse disorders, we will allow past diagnoses so long as there is no question of substance or alcohol dependence, the patient has not had substance abuse patterns in the year prior to enrollment, and other criteria regarding LSD and ecstasy use are met (see below). 2. Any history of psychotic symptoms 3. If female, any history of Premenstrual Dysphoric Disorder (PMDD), because PMDD has been shown to correlate with changes in 5-HT1A distribution in brain. 4. Any history of Lysergic acid diethylamide (LSD) use, because it may alter serotonin receptor properties. 5. History of ecstasy use more than 3 times in life, because it may alter serotonin receptor properties. 6. In women, irregular menses such that it will not be possible to determine the phase of the cycle. This is because previous data show that the phases of the menstrual cycle may affect 5-HT1A binding by radioligand. 7. Clinically significant laboratory abnormalities. 8. Psychotropic medication use (including benzodiazepines and illicit drugs) during the 21 days (42 days for fluoxetine/ Prozac, which has a longer half-life) prior to the PET scan. 9. Serious medical problems including but not limited to chronic neurological disease such as multiple sclerosis, autoimmune diseases or any cardiopulmonary disease that would increase risks associated with sedation. 10. Positive HIV status. 11. Metallic foreign bodies that would be affected by the MRI magnet, or fear of enclosed spaces likely to make the subject unable to undergo an MRI scan. 12. Head trauma resulting in a period of unconsciousness lasting longer than 10 minutes. 13. History of fetal alcohol syndrome or other neurodevelopmental disorder. 14. Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits. 15. Positive urine drug screen. 16. Inability to lie flat on camera bed for about 2.5 h 17. Pregnancy at time of scan (BetaHCG will be measured in all female patients within 24 hours of scan and must be negative)