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

Phase 2

Completed

Conditions: Premenstrual Dysphoric Disorder

Interventions: Drug: Oxytocin
Drug: Placebo

Registration Number: NCT02508103

Lead Sponsor: University of North Carolina, Chapel Hill

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 10

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Oxytocin, then Placebo	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
Placebo, then Oxytocin	Placebo	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
Oxytocin, then Placebo	Oxytocin	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
Placebo, then Oxytocin	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

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures