The Role of GABA and Neurosteroids in Premenstrual Dysphoric Disorder

The Role of GABA and Neurosteroids in Premenstrual Dysphoric Disorder

The purpose of the study proposed is to investigate the role of neurosteroids and GABA in the pathophysiology and treatment of premenstrual dysphoric disorder (PMDD) by 1) measuring cortical gama-aminobutyric acid levels (GABA levels) using nuclear magnetic resonance spectroscopy (MRS) during the follicular and mid-luteal phases of the menstrual cycle pre and post treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac®, Sarafem®), and 2) correlating cerebrospinal fluid (CSF) and plasma GABA and neurosteroid levels with cortical GABA levels at these same time points. Neurosteroids to be measured include allopregnanolone, pregnenolone, and pregnenolone sulfate. Findings from women with PMDD will be compared to those of healthy subjects.

Inclusion Criteria:

• Aged 18 - 45 years old and able to give voluntary written informed consent.
• Willing to complete a daily log of mood symptoms for 7 consecutive menstrual cycles: two menstrual cycles during the Screening Phase (Phase 1), one menstrual cycle during the Testing Phase (Phase 2), and four menstrual cycles during the Medication Treatment Phase and Post-Treatment Phase (Phase 3). All subjects who successfully complete Phases 1 and 2, and the Medication Treatment Phase, will be invited to participate in Phase 3 approximately three months later. Phase 3 will involve repeating all procedures conducted in Phase 2, including the daily log of mood symptoms.
• Meet DSM-IV criteria for premenstrual dysphoric disorder, confirmed by the Daily Record of Severity of Problems (DRSP; Endicott & Harrison) for 2 consecutive menstrual cycles (Phase 1). The DRSP is a self-rated symptom checklist, which requires individuals to rate their symptoms of PMDD according to the DSM-IV research criteria scale on a scale from 1 (symptom not present) to 6 (symptom extreme). During the last 7 days of the menstrual cycle compared to days 5-11, patients must have a 30% increase in their average (over 2 menstrual cycles) score for 5 of these 10 symptoms. Symptoms must be "not present" or "minimal" during the postmenstrual week.
• Average 19-item Hamilton Depression Rating Scale (HAM-D) scores < 5 during the follicular phase and > 16 during the luteal phase.
• Have regular menstrual cycles 28 to 32 days in length. Each of the screening cycles must be ovulatory as confirmed by plasma progesterone levels of >5 ng/ml during the luteal phase.

Exclusion Criteria:

• Presence of any other comorbid DSM-IV Axis I disorder.
• Meeting DSM-IV criteria for psychoactive substance (excluding nicotine) dependence within the preceding 4 months.
• A history of serious medical or neurological illness, including (but not limited to) major cardiovascular disease, severe hypertension, intracranial mass lesions, seizure disorder, severe hepatic or renal disease, unstable endocrine or metabolic disease, and unstable hematologic disease.
• Use of anticonvulsant or benzodiazepines within the last month.
• Use of psychotropic medication in last week (except as stated above).
• Use of steroid contraceptives within the previous 4 months, including birth control pill, birth control patch, birth control ring, and Depo-Provera®. Subjects will be asked to use abstinence or the barrier method (condoms) as forms of contraception in this study.
• Alcohol consumption greater than 7 drinks/week.
• Current pregnancy.
• Metallic implants.