Perimenopause-Related Mood and Behavioral Disorders

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.

- 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 40-60;

- 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 (> 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.