Stress & Premenstrual Symptoms Study

Among women with PMDD (premenstrual mood dysphoric disorder), baseline arousal is heightened
during the luteal phase of the menstrual cycle compared to the follicular phase, as measured
by acoustic startle response (ASR). Healthy female controls do not show cyclic changes in
this measure of physiologic arousal. It has been suggested that such heightened physiologic
arousal during the luteal phase may be due to differences in neurosteroid modulation of
GABA-A receptor function. Research indicates that women with premenstrual mood disorders
(PMDs) may have sub-optimal sensitivity to the progesterone metabolite allopregnanolone
(ALLO), a GABA-A receptor modulator. In animal models, intracerebroventricular injection of
corticotrophin releasing factor (CRF) increases amplitude of the acoustic startle response,
while ALLO administration attenuates this CRF-enhanced startle. CRF-enhanced startle is
mediated by the bed nucleus of the stria terminalis (BNST). Thus, ALLO appears to impact the
BNST and anxiety, versus the amygdala and acute fear. The proposed study will examine both
anticipatory anxiety and cued fear at baseline and with SSRI treatment. The magnitude of the
ASR with the former manipulation would reflect BNST activity which we hypothesize is
dysregulated in women with PMDD. Secondary aims are to examine the impact of luteal phase
treatment with a selective serotonin reuptake inhibitor (SSRI) on psychophysiology in women
with PMDs and to examine the relationship between affective symptoms, stress regulation and
immune function among these women, as well as associations with hormone levels and genetic
markers.

Inclusion Criteria:

Participants must be:

1. Aged 18 - 50 years, per self-report

2. Able to give written informed consent, per self-report

3. Fluent in written and spoken English

4. Have normal or corrected to normal hearing and vision, per self-report

5. Female participants must be experiencing regular menstrual cycles (24-39 days), per
self-report

6. Have a negative urine drug screen.

Exclusion Criteria:

Participants cannot have:

1. Use of an psychotropic medication anytime in the past 2 months, per self-report

2. Drug or alcohol abuse history within previous 2 years

3. Lifetime history of psychotic disorder including, schizophrenia, schizoaffective
disorder, major depression with psychotic features and bipolar disorder, per
self-report

4. Currently homeless, per self-report

5. History of any Axis I disorder other then specific phobia within the past 12 months,
per SCID interview

6. Active suicidal ideation (suicide plan or suicide attempt) within the previous 6
months, per self-report

7. Steroid hormone or hormonal contraceptive use in the past 6 months, per self-report,
except emergency contraceptive use

8. Pregnancy in the past year, per self-report. Pregnancy during the study is also
exclusionary. Participants must use a reliable, nonhormonal form of birth control
during the study. If a participant becomes pregnant, she must inform study staff.

9. Sensitive hearing, per self-report.