Mood, PMDD, Stress
Conditions
Keywords
Zoloft, premenstrual syndrome (PMS), Menses
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.
Interventions
DRUGSertraline
Sertraline will be provided at a dose of 50 mg daily for up to 3 weeks, depending on the length of a woman's luteal phase. Medication will be taken only during the luteal phase. Women will initiate sertraline treatment upon determining that they have ovulated (using a urine luteinizing hormone (LH) Kit) and remain on sertraline until onset of their next menstrual period at which time they will stop taking the medication.
Sponsors
National Institute of Mental Health (NIMH)
Johns Hopkins University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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 Structured Clinical Interview for Diagnostic and Statistical Manual (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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Controls do not receive sertraline. | 43 |
| Sertraline To determine the impact of short term luteal phase treatment with Sertraline 50mg tablets (PMD group only) on arousal regulation across the menstrual cycle.
Sertraline: Sertraline will be provided at a dose of 50 mg daily for up to 3 weeks, depending on the length of a woman's luteal phase. Medication will be taken only during the luteal phase. Women will initiate sertraline treatment upon determining that they have ovulated (using a urine LH Kit) and remain on sertraline until onset of their next menstrual period at which time they will stop taking the medication. | 41 |
| Total | 84 |
Baseline characteristics
| Characteristic | Control | Sertraline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants | 41 Participants | 84 Participants |
| Age, Continuous | 28.4 years STANDARD_DEVIATION 6.3 | 33.6 years STANDARD_DEVIATION 7.7 | 30.8 years STANDARD_DEVIATION 7.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 41 Participants | 84 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 10 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) White | 20 Participants | 23 Participants | 43 Participants |
| Region of Enrollment United States | 43 Participants | 41 Participants | 84 Participants |
| Sex: Female, Male Female | 43 Participants | 41 Participants | 84 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 23 |
| other Total, other adverse events | 0 / 0 | 0 / 23 |
| serious Total, serious adverse events | 0 / 0 | 0 / 23 |
Outcome results
Primary
Acoustic Startle Response (ASR) Magnitude Based on Menstrual Cycle Phase
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.
Time frame: Month 1 (Follicular), Month 2 (Luteal)
Population: 33 Controls and 24 PMDD (Sertraline) completed the Month 1 (Follicular) visit, and 27 Controls and 23 premenstrual mood dysphoric disorder (PMDD) completed the Month 2 (Luteal) visit. Assessments were done on 1 day of the Follicular phase and 1 day of the Luteal phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Acoustic Startle Response (ASR) Magnitude Based on Menstrual Cycle Phase | Month 1 (Follicular) | 54.2 t score | Standard Deviation 4.4 |
| Control | Acoustic Startle Response (ASR) Magnitude Based on Menstrual Cycle Phase | Month 2 (Luteal) | 56.4 t score | Standard Deviation 4.8 |
| Sertraline | Acoustic Startle Response (ASR) Magnitude Based on Menstrual Cycle Phase | Month 1 (Follicular) | 53.7 t score | Standard Deviation 4.7 |
| Sertraline | Acoustic Startle Response (ASR) Magnitude Based on Menstrual Cycle Phase | Month 2 (Luteal) | 53.3 t score | Standard Deviation 4.8 |
Comparison: Effect of group on differences in ASR t scores from follicular to luteal.p-value: 0.139Regression, Linear
Primary
Impact of Sertraline on ASR Magnitude
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.
Time frame: Month 2 (Luteal), Month 3 (Luteal)
Population: 27 Controls and 23 PMDD (Sertraline) completed Luteal Month 2, and 24 Controls and 23 PMDD completed Luteal Month 3. Assessments were done on 1 day of the Luteal phase in Month 2 and 1 day of the Luteal phase in Month 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Impact of Sertraline on ASR Magnitude | Month 2 (Luteal) | 56.4 t score | Standard Deviation 4.8 |
| Control | Impact of Sertraline on ASR Magnitude | Month 3 (Luteal) | 51.8 t score | Standard Deviation 4.6 |
| Sertraline | Impact of Sertraline on ASR Magnitude | Month 2 (Luteal) | 53.3 t score | Standard Deviation 4.8 |
| Sertraline | Impact of Sertraline on ASR Magnitude | Month 3 (Luteal) | 52.2 t score | Standard Deviation 5 |
p-value: 0.843Regression, Linear
Secondary
Interleukin 6 (IL-6) Level
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).
Time frame: Month 1 (Follicular ), Month 2 (Luteal )
Population: 38 participants in the Control group and 32 participants in the PMDD group had blood available for IL-6 measurement in the Follicular phase. 36 Controls and 32 PMDD had blood available for IL-6 in the Luteal 1 phase. Assessments were done on 1 day of the Follicular phase and 1 day of the Luteal phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Interleukin 6 (IL-6) Level | Month 1 (Follicular) | 0.4 picogram/milliliter (pg/mL) | Standard Deviation 0.19 |
| Control | Interleukin 6 (IL-6) Level | Month 2 (Luteal) | .59 picogram/milliliter (pg/mL) | Standard Deviation 0.46 |
| Sertraline | Interleukin 6 (IL-6) Level | Month 2 (Luteal) | .4 picogram/milliliter (pg/mL) | Standard Deviation 0.17 |
| Sertraline | Interleukin 6 (IL-6) Level | Month 1 (Follicular) | .34 picogram/milliliter (pg/mL) | Standard Deviation 0.15 |
p-value: 0.06t-test, 2 sided
Secondary
Tumor Necrosis Factor Alpha (TNF-alpha) Level
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).
Time frame: Month 1 (Follicular ), Month 2 (Luteal )
Population: 38 Controls and 32 PMDD had blood available to measure TNF-alpha in the Follicular phase. 36 Controls and 32 PMDD had blood available to measure TNF-alpha in the Luteal phase. Assessments were done on 1 day of the Follicular phase and 1 day of the Luteal phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Tumor Necrosis Factor Alpha (TNF-alpha) Level | Month 1 (Follicular ) | 1.27 pg/mL | Standard Deviation 0.32 |
| Control | Tumor Necrosis Factor Alpha (TNF-alpha) Level | Month 2 (Luteal ) | 1.27 pg/mL | Standard Deviation 0.36 |
| Sertraline | Tumor Necrosis Factor Alpha (TNF-alpha) Level | Month 1 (Follicular ) | 1.63 pg/mL | Standard Deviation 0.52 |
| Sertraline | Tumor Necrosis Factor Alpha (TNF-alpha) Level | Month 2 (Luteal ) | 1.54 pg/mL | Standard Deviation 0.31 |