• INCLUSION CRITERIA:

A. Group 1: Women with a history of postpartum depression:

1. A history of Diagnostic and Statistical Manual (DSM)-IV major depression or hypomanic/manic episode that occurred within three months of childbirth (as determined by a Structured Clinical Interview for the DSM (SCID) interview));
2. has been well for a minimum of one year;
3. a regular menstrual cycle for at least three months;
4. age 18-50;
5. not pregnant, not lactating and in good medical health;
6. medication free (including birth control pills);
7. no history of puerperal suicide attempts or psychotic episodes requiring hospitalization.

B. Group 2: Women with a history of Major Depressive Disorder

1. A history of DSM-IV major depression episode(s) occurring outside of pregnancy and not within three months postpartum;
2. has been well for a minimum of one year;
3. a regular menstrual cycle for at least three months;
4. age 18-50;
5. not pregnant, not lactating and in good medical health;
6. medication free (including birth control pills);
7. no history of suicide attempts or psychotic episodes requiring hospitalization.

C. Group 3: Normal Controls

1) Controls will meet all criteria specified except they must not have any past or present Axis I diagnosis or evidence of menstrual related mood disorders.

EXCLUSION CRITERIA:

Patients will not be permitted to enter this protocol if they have important clinical or laboratory abnormalities including any history of the following:

• endometriosis;
• undiagnosed enlargement of the ovaries;
• liver disease;
• breast cancer;
• a history of blood clots in the legs or lungs;
• undiagnosed vaginal bleeding;
• porphyria;
• diabetes mellitus;
• malignant melanoma;
• gallbladder or pancreatic disease;
• heart or kidney disease;
• cerebrovascular disease (stroke);
• cigarette smoking;
• a history of suicide attempts or psychotic episodes requiring hospitalization;
• recurrent migraine headaches;
• pregnancy (patients will be warned not to become pregnant during the study and will be advised to employ barrier contraceptive methods;
• pregnancy-related medical conditions such as hyperemesis gravidarum, pretoxemia and toxemia, deep vein thrombosis (DVT) and bleeding diathesis;
• Any woman with a first degree relative (immediate family) with premenopausal breast cancer or breast cancer presenting in both breasts or any woman who has multiple family members (greater than three relatives) with postmenopausal breast cancer will also be excluded from participating in this protocol;
• Any woman meeting the Stages of Reproductive Aging Workshop Criteria (STRAW) for the perimenopause will be excluded from participation. Specifically, we will exclude any woman with an elevated plasma follicle stimulating hormone (FSH) level (greater than or equal to 14 IU/L) and with menstrual cycle variability of > 7 days different from their normal cycle length;
• Subjects who are unable to provide informed consent;
• National Institute of Mental Health (NIMH) employees and staff and their immediate family members will be excluded from the study per NIMH policy.