• PATIENT/VOLUNTEER INCLUSION CRITERIA:

Cross-sectional Screening: The perimenopausal subjects of this protocol will be women who meet the following inclusion criteria:

History within the last one year of at least one month with perimenopause-related mood or behavioral disturbances of at least moderate severity - that is, disturbances that are distinct in appearance and associated with a notable degree of functional impairment;

Age 40-60;

History of the onset of menstrual irregularity during the past six months but not greater than one year of amenorrhea (i.e., not postmenopausal);

Biological evidence of a deterioration of normal ovarian activity, specifically, plasma FSH levels persistently elevated (greater than 14 IU/L) drawn at two week intervals over a period of eight weeks;

No prior estrogen replacement therapy for treatment of perimenopausal physical or emotional symptoms within the last six months; and.

In good medical health

Subjects must be competent to comprehend the purpose of the screening process and to provide written informed consent and be willing to participate in NIMH IRB approved research protocols.

CONTROL GROUP INCLUSION CRITERIA:

A control group of age-matched perimenopausal women who meet patient selection criteria with the exception of the presence of mood or behavioral disorders will also be sought.

CONTROL GROUP EXCLUSION CRITERIA:

Subjects should have no general medical illness that is primary (i.e., appears to be causing the mood disorder);

Current alcohol or substance use or dependence (excluding nicotine) of sufficient magnitude to require independent, concurrent treatment intervention (e.g., antabuse or opiate treatment, but not including self-help groups)

LONGITUDINAL SCREENING INCLUSION CRITERIA:

Pre-perimenopausal women will be women who meet the following inclusion criteria:

Regular menstrual cycle function (21-34 days);

Absence of current mood or behavioral disturbance as determined by a structured diagnostic interview;

Plasma gonadotropin levels in pre-perimenopausal range (less than 14 IU/L);

In good medical health; and

Medication free.

GENETIC STUDIES INCLUSION CRITERIA:

Unaffected family members of women with perimenopausal depression will be admitted for genetic studies only.

First degree relatives of women with confirmed perimenopausal depression, who do not have perimenopausal depression as defined in this protocol.