Premenstrual Dysphoric Disorder
Conditions
Keywords
Premenstrual Dysphoric Disorder, Premenstrual Syndrome, PMS, PMDD
Brief summary
This research study will look at brain and symptom differences among women with severe premenstrual mood symptoms. One goal of this study is to look at the effects of taking a nasal spray containing oxytocin (a hormone made in the brain) on brain areas involved in emotion regulation while viewing pictures during a neuroimaging (fMRI) session. The investigators will also look at whether oxytocin improves premenstrual mood symptoms.
Detailed description
Purpose: The primary objective of this pilot study is to use functional neuroimaging techniques to begin to identify the central brain networks that may contribute to impairment in emotion regulation, interpersonal relationships, and marital and family function in women with premenstrual dysphoric disorder (PMDD), particularly for those women who also have a history of early life abuse (ELA). Based on the evidence that the mammalian neuropeptide oxytocin (OT), best known for its role in lactation and parturition, plays a seminal role in social affiliation, emotion regulation, attachment, maternal behavior, trust, and protection against stress; and because OT neural pathways and receptors are prominently expressed in brain regions involved in emotion regulation and maternal/affiliative behavior; the study will: 1) use intranasal OT administration as a probe to assess whether it modifies activation of brain regions involved in emotion regulation in response to an emotional processing task; and 2) whether daily intranasal OT administration during the premenstrual phase improves symptoms in women with PMDD with or without a history of ELA.
Interventions
DRUGOxytocin
Intranasal Oxytocin spray (40 IU, 3x/day) self-administered during laboratory testing session and then for 4-5 days until menses begins
DRUGPlacebo
Intranasal Placebo spray (3x/day) self-administered during laboratory testing session and then for 4-5 days until menses begins
Sponsors
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 52 Years
Healthy volunteers
Yes
Inclusion criteria
* In order to be eligible to enter this study, subjects will have met PMDD Study Entry Criteria in the diagnostic feeder study (IRB# 05-3000) * 18 to 52 years of age * Regular menstrual cycles * Ability to give informed consent
Exclusion criteria
* current psychiatric diagnosis of substance abuse or claustrophobia (fear of closed places) * pregnancy (based on urine pregnancy test) or breastfeeding * use of psychiatric medication (e.g. for depression, anxiety), hormonal medication, other agents that alter mood or thinking, or street drugs * any foreign iron or steel metal objects in the body, such as a pacemaker, shrapnel, metal plate, certain types of tattoos, or metal debris
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Premenstrual Symptom Severity | During the late luteal phase of two consecutive menstrual cycles (an average of 3-5 days of treatment) | The investigators will analyze premenstrual symptom severity ratings during the late luteal phase of two consecutive menstrual cycles to assess the effects of intranasal oxytocin (vs. placebo) on premenstrual symptom severity. Daily premenstrual symptoms were measured using the Daily Record of Severity of Problems (DRSP; Endicott et al., 2006). Across 24 items representing emotional, physical, and behavioral symptoms, participants indicated the degree to which the problems have been experienced today: 1-Not at all, 2-Minimal, 3-Mild, 4-Moderate, 5-Severe, or 6-Extreme. For each participant, we calculated a total score by summing all 24 items. We then calculated a mean total score for each condition by averaging all participants total scores in a given condition. Higher scores represent greater symptoms. Range of total score is 24 to 144. |
| Amygdala Response to Cognitive-emotional Processing Task During Functional Magnetic Resonance Imaging (fMRI) | 1 hour of scanning during the late luteal phase of two consecutive menstrual cycles | During fMRI scanning, the investigators will assess the effects of intranasal oxytocin (vs. placebo) on amygdala response to cognitive-emotional processing task (Hariri et al., 2006) during the late luteal phase of two consecutive menstrual cycles. Amygdala reactivity was assessed by extracting a contrast of parameter estimate (COPE) for each region (left and right amygdala). Regions were defined using binarized Harvard-Oxford Subcortical Atlas masks. The parameter estimate was the average estimate of all voxels in each region for the task contrast of viewing Faces vs. Shapes. We used neuroimaging software package FSL to calculate and extract these parameter estimates. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oxytocin, Then Placebo Participants were randomized to receive Intransal Oxytocin for late luteal phase administration during one menstrual cycle, then received Intranasal Placebo for late luteal phase administration of a subsequent menstrual cycle.
Intranasal Oxytocin spray (40 IU, 3x/day) for 4-5 days; Intranasal Placebo spray (3x/day) for 4-5 days | 5 |
| Placebo, Then Oxytocin Participants were randomized to receive Intransal Placebo for late luteal phase administration during one menstrual cycle, then received Intranasal Oxytocin for late luteal phase administration of a subsequent menstrual cycle.
Intranasal Oxytocin spray (40 IU, 3x/day) for 4-5 days; Intranasal Placebo spray (3x/day) for 4-5 days | 5 |
| Total | 10 |
Baseline characteristics
| Characteristic | Oxytocin, Then Placebo | Placebo, Then Oxytocin | 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 | 5 Participants | 5 Participants | 10 Participants |
| Age, Continuous | 36.4 years | 36.8 years | 36.6 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 4 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 2 Participants | 7 Participants |
| Region of Enrollment United States | 5 participants | 5 participants | 10 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 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 / 10 | 0 / 10 |
| other Total, other adverse events | 4 / 10 | 1 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Amygdala Response to Cognitive-emotional Processing Task During Functional Magnetic Resonance Imaging (fMRI)
During fMRI scanning, the investigators will assess the effects of intranasal oxytocin (vs. placebo) on amygdala response to cognitive-emotional processing task (Hariri et al., 2006) during the late luteal phase of two consecutive menstrual cycles. Amygdala reactivity was assessed by extracting a contrast of parameter estimate (COPE) for each region (left and right amygdala). Regions were defined using binarized Harvard-Oxford Subcortical Atlas masks. The parameter estimate was the average estimate of all voxels in each region for the task contrast of viewing Faces vs. Shapes. We used neuroimaging software package FSL to calculate and extract these parameter estimates.
Time frame: 1 hour of scanning during the late luteal phase of two consecutive menstrual cycles
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin | Amygdala Response to Cognitive-emotional Processing Task During Functional Magnetic Resonance Imaging (fMRI) | Left Amygdala | 0.89 parameter estimate | Standard Deviation 0.48 |
| Oxytocin | Amygdala Response to Cognitive-emotional Processing Task During Functional Magnetic Resonance Imaging (fMRI) | Right Amygdala | 1.14 parameter estimate | Standard Deviation 0.57 |
| Placebo | Amygdala Response to Cognitive-emotional Processing Task During Functional Magnetic Resonance Imaging (fMRI) | Left Amygdala | 0.95 parameter estimate | Standard Deviation 0.81 |
| Placebo | Amygdala Response to Cognitive-emotional Processing Task During Functional Magnetic Resonance Imaging (fMRI) | Right Amygdala | 1.22 parameter estimate | Standard Deviation 1.25 |
Primary
Change in Premenstrual Symptom Severity
The investigators will analyze premenstrual symptom severity ratings during the late luteal phase of two consecutive menstrual cycles to assess the effects of intranasal oxytocin (vs. placebo) on premenstrual symptom severity. Daily premenstrual symptoms were measured using the Daily Record of Severity of Problems (DRSP; Endicott et al., 2006). Across 24 items representing emotional, physical, and behavioral symptoms, participants indicated the degree to which the problems have been experienced today: 1-Not at all, 2-Minimal, 3-Mild, 4-Moderate, 5-Severe, or 6-Extreme. For each participant, we calculated a total score by summing all 24 items. We then calculated a mean total score for each condition by averaging all participants total scores in a given condition. Higher scores represent greater symptoms. Range of total score is 24 to 144.
Time frame: During the late luteal phase of two consecutive menstrual cycles (an average of 3-5 days of treatment)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Change in Premenstrual Symptom Severity | 25.05 units on a scale | Standard Deviation 16.74 |
| Placebo | Change in Premenstrual Symptom Severity | 27.36 units on a scale | Standard Deviation 13.8 |