Stress & Premenstrual Symptoms Study

Phase 4

Completed

Conditions: PMDD
Stress
Mood

Interventions: Drug: Sertraline

Registration Number: NCT02777372

Lead Sponsor: Johns Hopkins University

Brief Summary: This study that aims to evaluate the psychophysiology of premenstrual mood disorders (PMDs) at baseline and after treatment with sertraline. Participants will include women with PMDs and healthy female controls. Participation involves a baseline visit to determine eligibility and three study visits that include questionnaires and stress reactivity assessment via an acoustic startle paradigm. Female participants with PMDs will receive sertraline during the premenstrual phase.

Detailed Description: Among women with premenstrual mood dysphoric disorder (PMDD), 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 Gamma-aminobutyric acid (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. The primary aim of this study is to examine differences in ASR by menstrual cycle phase (follicular, luteal) and group (control, PMDD). Secondary aim is to examine the impact of luteal phase treatment with a selective serotonin reuptake inhibitor (SSRI) on psychophysiology in women with PMDs. An exploratory aim is to examine immune function among these women.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 84

Inclusion Criteria

Participants must be:

Aged 18 - 50 years, per self-report
Able to give written informed consent, per self-report
Fluent in written and spoken English
Have normal or corrected to normal hearing and vision, per self-report
Female participants must be experiencing regular menstrual cycles (24-39 days), per self-report
Have a negative urine drug screen.

Exclusion Criteria

Participants cannot have:

Use of an psychotropic medication anytime in the past 2 months, per self-report
Drug or alcohol abuse history within previous 2 years
Lifetime history of psychotic disorder including, schizophrenia, schizoaffective disorder, major depression with psychotic features and bipolar disorder, per self-report
Currently homeless, per self-report
History of any Axis I disorder other then specific phobia within the past 12 months, per Structured Clinical Interview for Diagnostic and Statistical Manual (SCID) interview
Active suicidal ideation (suicide plan or suicide attempt) within the previous 6 months, per self-report
Steroid hormone or hormonal contraceptive use in the past 6 months, per self-report, except emergency contraceptive use
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.
Sensitive hearing, per self-report.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sertraline	Sertraline	To determine the impact of short term luteal phase treatment with Sertraline 50mg tablets (PMDD group only) on acoustic startle response across the menstrual cycle. Sertraline 50 mg tablets are administered daily from ovulation until menses onset.

Primary Outcome Measures

Name	Time	Method
Acoustic Startle Response (ASR) Magnitude Based on Menstrual Cycle Phase	Month 1 (Follicular), Month 2 (Luteal)	Acoustic startle response (ASR) is measured during the follicular and luteal phase of the menstrual cycle in controls and those with PMDD. Magnitude of ASR is measured using the eyeblink reflex, by recording activity from the orbicularis oculi muscle. Recording is performed via two surface disk electrodes (Ag-AgCl) applied underneath the left eye; one in line with the pupil and one 1-2 cm lateral to the first one. For the primary outcome of baseline ASR magnitude over the menstrual cycle, peak amplitude of the blink reflex was determined in the 20-120-ms time frame following stimulus onset relative to baseline (baseline is the average baseline electromyography (EMG) level for the 50 ms immediately preceding auditory stimulus onset). ASR is measured in microvolts, and raw ASR results are standardized to t-scores. Higher ASR t-score indicates greater contraction of the the orbicularis oculi muscle. A t-score of 50 indicates the population mean with a standard deviation of 10.
Impact of Sertraline on ASR Magnitude	Month 2 (Luteal), Month 3 (Luteal)	This outcome examines the impact of luteal phase treatment with a selective serotonin reuptake inhibitor (SSRI) (PMDD group only) on acoustic startle response (ASR). ASR is measured using the eyeblink reflex, measured by recording activity from the orbicularis oculi muscle. Recording is performed via two surface disk electrodes (Ag-AgCl) applied underneath the left eye; one in line with the pupil and one 1-2 cm lateral to the first one. Peak amplitude of the blink reflex is determined in the 20-120-ms time frame following stimulus onset. PMDD participants complete test day 3 (Luteal Month 3) while on sertraline and their ASR magnitude will be compared to their previous luteal test day (Luteal Month 2). ASR is measured in microvolts, and raw ASR results are standardized to t-scores. Higher ASR t-score indicates greater contraction of the the orbicularis oculi muscle. A t-score of 50 indicates the population mean with a standard deviation of 10.

Secondary Outcome Measures

Name	Time	Method
Interleukin 6 (IL-6) Level	Month 1 (Follicular ), Month 2 (Luteal )	Blood samples were collected to measure serum interleukin-6 (IL-6). IL-6 levels were compared in the follicular and luteal phases, between Control and PMDD groups. Levels are measured in picogram/milliliter (pg/mL).
Tumor Necrosis Factor Alpha (TNF-alpha) Level	Month 1 (Follicular ), Month 2 (Luteal )	Blood samples were collected to measure serum TNF-alpha levels in the Follicular and Luteal 1 phases. Levels are measured in picogram/milliliter (pg/mL).