Perimenopause-Related Mood and Behavioral Disorders

The purpose of this study is to investigate mood and behavior changes in the time period surrounding and including menopause. This is an observational study; volunteers who participate will not receive any new or experimental therapies.

Controversy exists regarding the relationship between estrogen and progesterone (gonadal steroid) changes and midlife-onset depression. This study will examine the role of gonadal steroids in perimenopausal mood and behavioral disorders.

Perimenopausal women with depression symptoms and a control group of healthy perimenopausal volunteers will be compared to identify correlates of the occurrence of depression. Participants with depressive symptoms may also participate in companion studies that will test the antidepressant efficacy of phytoestrogens and selective estrogen receptor modulators (SERMS).

A group of younger pre-perimenopausal women with normal menstrual cycle functioning will be followed through menopause in an effort to confirm the association of depression onset with changes in reproductive endocrine functioning.

Controversy exists regarding the relevance of changes in gonadal steroids for midlife onset depressions. The purpose of this protocol is to allow for the careful screening of patients and healthy volunteers for participation in research protocols that examine the role of gonadal steroids in depressions occurring during the perimenopause and for the collection of natural history data. Women in this protocol will undergo an evaluation which may include: a psychiatric diagnostic interview; rating scales; a medical history; a physical exam; blood and urine laboratory evaluation; and a request for medical records. The data collected may also be linked with data from other perimenopausal depression protocols (e.g., DNA, psychophysiology tests, treatment studies, etc.) for the purposes of better understanding the diagnosis, pathophysiology, and treatment response of women with depression during the perimenopause.Upon conclusion of the screening process, participants will either be offered entry into a research protocol and will sign the appropriate informed consent, or will be considered not appropriate for participation in research and will be referred back into the community. The second purpose of this protocol is to permit the identification of premenopausal women who are followed longitudinally through the menopause transition in an effort to confirm the association of depression onset with change in reproductive endocrine function. This protocol, then, serves as a screening and evaluation protocol to recruit subjects who are characterized with standard measures in this protocol and then offered participation in related studies.

Eligibility Criteria:
* INCLUSION CRITERIA:
* Perimenopausal Subjects:

  * 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 40-65;
  * 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 (\> 14IU/L) (as recommended by the Stages of Reproductive Aging Workshop criteria (106)) 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.
* 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.
* Premenopausal women will be women who meet the following inclusion criteria for the longitudinal study participants:

  * 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 (\<14 IU/L);
  * In good medical health; and
  * Medication free.

EXCLUSION CRITERIA:

* Primary general medical illness (i.e., appears to be causing the mood disorder);
* Current antidepressant therapy (since this is a screening protocol for subsequent treatment studies in which participants must be untreated). Antidepressants will not be withheld from participants who need or want them;
* Current alcohol or substance abuse 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);
* Pregnant or lactating women;
* Subjects who are unable to provide informed consent.
* NIMH employees, staff and their immediate family members will be excluded from the study per NIMH policy.