The overarching objective that has guided my research endeavors, collaborations and training opportunities has been to determine the mechanism by which sex hormones and neurosteroids interact with neurotransmitters to modulate behavior, mood and cognition in women. With my mentored K award, I have developed a unique program of clinical research that relies heavily on knowledge gained from molecular and basic neuroscience to inform our investigations of the pathogenesis of premenstrual dysphoric disorder (PMDD), postnatal depression (PPD) and perimenopausal mood and cognitive changes. To this end, I have employed proton magnetic resonance spectroscopy (1H-MRS) to obtain in vivo measures of amino acid neurotransmitter (AANt) concentrations under various hormonal conditions and pathologic states. Our 1H-MRS findings confirm that AANt levels are altered by changes in the neuroendocrine milieu. The research plan that I proposes herein will take full advantage of information obtained from our previous H-MRS studies to begin to tease apart the effects of individual neuroactive steroids on AANts and to inform our application of more dynamic MRS techniques to examine AANt synthesis and cycling in healthy menstruating women and those with PMDD.
My aims during K02 funding are to (1) pursue studies of the biochemistry of AANt, (2) become proficient in MRS theory, data acquisition and analysis, (3) develop expertise in neurosteroid biosynthesis and measurement, and (4) advance my understanding of statistical models which are frequently applied to longitudinal samples (random effects). In addition, two projects are proposed (1) """"""""The Impact of Fluoxetine Treatment on Neurosteroidogenesis and Cortical GABA and Glutamate Concentrations in Women with PMDD,"""""""" funded by my recent R01 and (2) H-MRS and C-MRS Investigation of the Differential Effects of Estradiol, Progesterone and AIIopregnanolone on Cortical AANt Concentrations, Glutamate-Glutamine Cycling and GABA Synthesis in Women With & Without PMDD. As my K23 funding is drawing to an end (12/01/04), timely funding of this K02 grant will insure that I can focus on the career development plan and projects outlined herein. Without K02 funding, I will have to assume additional, non-research related activities. My translational research and educational endeavors over the past 4 years have insured that I am uniquely poised to advance our understanding of the neuroendocrine contribution to mood and behavior in women. With the full support of our Departments of Psychiatry and Obstetrics/Gynecology for my promotion to Associate Professor in July 2004, I am situated in an intellectually rich and supportive academic community that is certain to further my career development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02MH073090-04
Application #
7334152
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Meinecke, Douglas L
Project Start
2005-01-14
Project End
2009-12-31
Budget Start
2008-01-01
Budget End
2008-12-31
Support Year
4
Fiscal Year
2008
Total Cost
$125,388
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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
Epperson, C Neill; Amin, Zenab; Ruparel, Kosha et al. (2012) Interactive effects of estrogen and serotonin on brain activation during working memory and affective processing in menopausal women. Psychoneuroendocrinology 37:372-82
Epperson, C Neill; Pittman, Brian; Czarkowski, Kathryn A et al. (2011) Impact of atomoxetine on subjective attention and memory difficulties in perimenopausal and postmenopausal women. Menopause 18:542-8
Epperson, C Neill; Toll, Benjamin; Wu, Ran et al. (2010) Exploring the impact of gender and reproductive status on outcomes in a randomized clinical trial of naltrexone augmentation of nicotine patch. Drug Alcohol Depend 112:1-8
Beech, Robert D; Lowthert, Lori; Leffert, Janine J et al. (2010) Increased peripheral blood expression of electron transport chain genes in bipolar depression. Bipolar Disord 12:813-24
Shahar, Golan; Porcerelli, John H; Kamoo, Ray et al. (2010) Defensive projection, superimposed on simplistic object relations, erodes patient-provider relationships in high-risk pregnancy: an empirical investigation. J Am Psychoanal Assoc 58:953-74
Forray, Ariadna; Focseneanu, Mariel; Pittman, Brian et al. (2010) Onset and exacerbation of obsessive-compulsive disorder in pregnancy and the postpartum period. J Clin Psychiatry 71:1061-8
Guille, Constance; Speller, Heather; Laff, Rachel et al. (2010) Utilization and barriers to mental health services among depressed medical interns: a prospective multisite study. J Grad Med Educ 2:210-4
Forray, Ariadna; Mayes, Linda C; Magriples, Urania et al. (2009) Prevalence of post-traumatic stress disorder in pregnant women with prior pregnancy complications. J Matern Fetal Neonatal Med 22:522-7
Wakil, Laura; Epperson, C Neill; Gonzalez, Juan et al. (2009) Neonatal outcomes with the use of lamotrigine for bipolar disorder in pregnancy and breastfeeding: a case series and review of the literature. Psychopharmacol Bull 42:91-8

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