Impact of GABA-Enhancing Agents on Cortical GABA Concentrations Across the Menstrual Cycle in Women

The Impact of GABA-Enhancing Agents on Cortical GABA Concentrations Across the Menstrual Cycle in Women

The goal of this series of challenge studies is to examine the impact of menstrual cycle phase on cortical GABA response to administration of agents with either direct (benzodiazepines) or indirect (progesterone, fluoxetine) GABA modulating properties. While the impact of these agents on cortical GABA levels in women with premenstrual dysphoric disorder (PMDD) is of interest, this study is designed primarily for those women without a psychiatric illness.

Inclusion Criteria:

• Women ages 18-45 and able to give voluntary written informed consent;
• Regular menstrual periods of 24-35 days in length;
• Body mass index 18.5 to 30 kg/m2;
• No past or present DSM-IV psychiatric or substance dependence diagnosis by structured diagnostic interview (SCID-NP); no substance abuse history within the previous 2 years;
• Absence of mood symptoms across the menstrual cycle during one month of prospective daily ratings with the Daily Record of Severity of Problems (DRSP); the DRSP is based on the DSM-IV research criteria for premenstrual dysphoric disorder (PMDD) and has been used in numerous studies to confirm the presence or absence of significant premenstrual mood and behavioral difficulties;
• Must be willing and able to participate in at least three of the four challenge paradigms.

Exclusion Criteria:

• Medical, neurologic or cerebrovascular disorder (CVA, seizure disorder, etc.);
• Family history of first degree relative with an Axis I psychiatric or substance dependence disorder (excepting alcohol and nicotine) (per subject report);
• Current treatment with psychoactive medication;
• Diabetes controlled by means other than diet;
• Use of steroid contraceptives (any method involving hormones) within the previous 4 months;
• Habitual consumption of more than 7 alcoholic drinks per week or more than 2 drinks on any particular occasion; must be willing to abstain from alcohol consumption for 48 hours prior to each 1H-MRS scan;
• Implanted metallic devices.