Emotional Processing and Oxytocin Mechanisms in Premenstrual Dysphoric Disorder: A Pilot Study

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.

Study Overview

• Status: Completed
• Conditions: Premenstrual Dysphoric Disorder
• Intervention / Treatment: Drug: Oxytocin; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • University of North Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Oxytocin; Intranasal Oxytocin spray (40 IU, 3x/day) self-administered during laboratory testing session and then for 4-5 days until menses begins; Drug: Placebo; Intranasal Placebo spray (3x/day) self-administered during laboratory testing session and then for 4-5 days until menses begins
Experimental: Placebo, then Oxytocin; Participants were randomized to receive Intranasal Placebo for late luteal phase administration during one menstrual cycle, then received Intransal 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	Drug: Oxytocin; Intranasal Oxytocin spray (40 IU, 3x/day) self-administered during laboratory testing session and then for 4-5 days until menses begins; Drug: Placebo; Intranasal Placebo spray (3x/day) self-administered during laboratory testing session and then for 4-5 days until menses begins

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	During the late luteal phase of two consecutive menstrual cycles (an average of 3-5 days of treatment)
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.	1 hour of scanning during the late luteal phase of two consecutive menstrual cycles

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Investigators: Principal Investigator: Susan Girdler, PH.D., UNC-Chapel Hill

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: July 22, 2015
• First Submitted That Met QC Criteria: July 22, 2015
• First Posted (Estimate): July 24, 2015

Study Record Updates

• Last Update Posted (Actual): June 27, 2017
• Last Update Submitted That Met QC Criteria: May 23, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: PMS; PMDD; Premenstrual Syndrome; Premenstrual Dysphoric Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Mood Disorders; Depressive Disorder; Menstruation Disturbances; Premenstrual Syndrome; Disease; Premenstrual Dysphoric Disorder; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: 14-1153