After a year and a half on the faculty in the Departments of Psychiatry and Obstetrics and Gynecology, I find myself at a crossroads in my career development. I have been involved primarily in clinical postpartum mood disorders and obsessive compulsive disorders research. However, my clinical and scientific interests have shifted. During my tenure as the Director of the Yale Behavioral Gynecology Program, I have developed an appreciation for the complex interplay between neuroactive steroids and the neurochemistry involved in regulation of mood and cognition. In addition, I have developed basic skills in proton-magnetic resonance spectroscopy (1H-MRS), a novel, non-invasive method to quantify in vivo amino acid neurotransmitters. I have designed the K23 award to enable me to pursue a five-year comprehensive research-training plan. This plan will provide me with the skills necessary to become an independent investigator who can apply MRS techniques to determine the impact of neurosteroids on GABA and glutamate neurotransmission as they reltate to the pathophysiology and treatment of premenstrual dysphoric disorder (PMDD). Without support from a K23 award, I would be required to continue my significant administrative and clinical duties as the director of a busy clinical program and would not be afforded the opportunity to make this shift in my scientific career. We have obtained exciting pilot data using 1H-MRS demonstrating fluctuations in cortical GABA levels across the menstrual cycle of women with PMDD and health menstruating controls with between group differences in the fluctuation pattern. I propose to continue these investigations with three goals. 1) To conduct the first longitudinal (across the menstrual cycle) characterization of both frontal and occipital cortex GABAergic and glutamatergic systems in healthy menstruating women and those with PMDD. 2) To determine the relationship between neuroactive steroids and amino acid neurotransmitter levels across the menstrual cycle. Amd 3) To determine whether the selective serotonin reuptake inhibitor fluoxetine exert its therapeutic effect in the treatment of PMDD via modulation of neuroactive steroids and/or GABAergic and/or glutamateric function. I have identified several key areas where I will require additional training in order to advance the use of 1H-MRS techniques to the study of PMDD. These areas include; 1) nuclear magnetic resonance application of reproductive endocrinology to PMDD research, 3) neurochemistry and kinetic modeling, and 4) neuropharmacology and clinical trials methodologies. Under the mentorship of my Yale mentors Drs. Krystal, Rothman, and Naftolin and my extra-mural mentors Drs. Rubinow and Schmidt, the career development program outlined in this program is certain to prepare me for a career as an neuroendocrinologist who can utilize MRS technology to study the impact of neuroactive steroids on brain neurochemistry.
| Hantsoo, Liisa; Czarkowski, Kathryn A; Child, Josiah et al. (2014) Selective serotonin reuptake inhibitors and endothelial function in women. J Womens Health (Larchmt) 23:613-8 |
| Hantsoo, Liisa; Ward-O'Brien, Deborah; Czarkowski, Kathryn A et al. (2014) A randomized, placebo-controlled, double-blind trial of sertraline for postpartum depression. Psychopharmacology (Berl) 231:939-48 |
| Roomruangwong, Chutima; Tangwongchai, Sookjaroen; Pittman, Brian P et al. (2009) Predictors of anxiety symptoms in the gynecological outpatient setting: The Thai experience. Int J Psychiatry Clin Pract 13:91-9 |
| Epperson, Cynthia Neill; Pittman, Brian; Czarkowski, Kathryn Ann et al. (2007) Luteal-phase accentuation of acoustic startle response in women with premenstrual dysphoric disorder. Neuropsychopharmacology 32:2190-8 |
| Epperson, C Neill; Amin, Zenab; Naftolin, Frederick et al. (2007) The resistance to depressive relapse in menopausal women undergoing tryptophan depletion: preliminary findings. J Psychopharmacol 21:414-20 |
| Epperson, C Neill; Gueorguieva, Ralitza; Czarkowski, Kathryn A et al. (2006) Preliminary evidence of reduced occipital GABA concentrations in puerperal women: a 1H-MRS study. Psychopharmacology (Berl) 186:425-33 |
| Amin, Zenab; Gueorguieva, Ralitza; Cappiello, Angela et al. (2006) Estradiol and tryptophan depletion interact to modulate cognition in menopausal women. Neuropsychopharmacology 31:2489-97 |
| Epperson, C Neill; O'Malley, Stephanie; Czarkowski, Kathryn A et al. (2005) Sex, GABA, and nicotine: the impact of smoking on cortical GABA levels across the menstrual cycle as measured with proton magnetic resonance spectroscopy. Biol Psychiatry 57:44-8 |
| Sanacora, Gerard; Gueorguieva, Ralitza; Epperson, C Neill et al. (2004) Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry 61:705-13 |
| Epperson, C Neill; Terman, Michael; Terman, Jiuan Su et al. (2004) Randomized clinical trial of bright light therapy for antepartum depression: preliminary findings. J Clin Psychiatry 65:421-5 |
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