Characterizing the Neural Substrates of Irritability in Women: an Experimental Neuroendocrine Model

Inclusion Criteria

Participants will include healthy, euthymic 22-45 year old women with a history of postpartum depression (n=15) and women without such a history (n=15). Thus, only participants capable of giving informed consent will be enrolled. Participants will be compensated upon completion of the study.

Inclusion Criteria. Group 1: Women with a history of perinatal depression

• A history of a the Diagnostic Statistic Manual of Mental Disorders - fifth edition (DSM-V) major depression episode that occurred within 6 weeks of childbirth (as determined by a SCID interview) and remitted at least one year prior to enrollment in the study;
• has been well for a minimum of one year;
• a regular menstrual cycle for at least three months;
• age 22-45;
• medication free (including birth control pills);.

Group 2: Healthy Controls

• Controls will meet all inclusion criteria specified above except they must not have any past or present Axis I diagnosis or evidence of menstrually related mood disorders.

A structured clinical interview for DSM-V (SCID) will be administered to all women prior to study entry. Any woman with a current axis I psychiatric diagnosis will be excluded from participating in this protocol.

Exclusion Criteria

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

• current axis I psychiatric diagnosis (based on a structured clinical interview for DSM-V (SCID);
• 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 with aura;
• pregnancy-related medical conditions such as hyperemesis gravidarum, preeclampsia 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 perimenopause will be excluded from participation. Specifically, the investigators will exclude any woman with an elevated plasma follicle stimulating hormone (FSH) level (> 14 IU/L) and with menstrual cycle variability of > 7 days different from their normal cycle length.

Pregnant women will be excluded from participation (patients will be warned not to become pregnant during the study and will be advised to employ barrier contraceptive methods), and women who become pregnant (although unlikely because of the hormone manipulation) will be withdrawn. The use of leuprolide acetate is not recommended during pregnancy. Prior to treatment, a complete physical, including a serum β-human chorionic gonadotropin (HCG) test for pregnancy. Participants will be seen at the outpatient clinic on a regular biweekly basis. All participants will be required to use non-hormonal forms of birth control (e.g., barrier methods) to avoid pregnancy during this study. Participants will also undergo urine toxicology and pregnancy tests on the day of each of the two fMRI scans. If a woman becomes pregnant during the study, she will not complete the fMRI scan, and the hormone protocol will be discontinued.