This KO2 application seeks support that is essential for Dr. Sanacora's continued career development as a newly-independent clinical researcher. Funded by a NIMH K08 mentored career award (K08-MH-01715) Dr. Sanacora has attained considerable expertise in the use of magnetic resonance spectroscopy as a tool to investigate the role of amino acid neurotransmitter systems in the pathophysiology and treatment of mood disorders over the past 5 years. Thanks to the mentorship Dr. Sanacora received and the excellent environment provided to him through the Magnetic Resonance Center and the Department of Psychiatry at Yale he demonstrated considerable research productivity during this time as evidenced by his peer-reviewed publications and a recently-awarded RO1 (MH071676-01, G. Sanacora, P.I.). However, this K08 expired 6/31/04. This KO2 award is vital for sustaining Dr. Sanacora's current full-time research focus and for assuring his successful matriculation into a fully independent investigator. Justification for the award is provided by a comprehensive 5-year Career Development Plan that builds on his current expertise in the study of amino acid neurotransmitter contributions to mood disorders and the MRS methodologies used to investigate this area. Specifically, his goals are to acquire specialized skills in several additional areas that will make it possible for him to extend this work into areas of more direct scientific and clinical significance: 1) 13C-glucose MRS methods to measure rates of synthesis and cycling, 2) 13C-acetate studies to probe glial cell involvement in mood disorder pathology, 3) clinical trial experience to allow him to address the potential clinical usefulness of drugs targeting the amino acid neurotransmitter systems, and 4) basic molecular neurobiology related to amino acid neurotransmission that will enable him to continue to conduct relevant translational research in mood disorders. Intensive training is provided by an integrated curriculum of intramural coursework, extramural didactics, individualized preceptorships, interactive symposia, and research-related organizational meetings. Three representative studies are included to illustrate how the development of these skills will be used to advance the line of research that was initiated in his previous K08 award into the realms of pathophysiology and clinical practice. Thus, receiving this award would allow him the opportunity to improve the basic understanding of how the amino acid neurotransmitter systems and glial cell pathology contribute to the neurobiology of mood disorders. This work has direct clinical relevance since it is likely to lead to the development of novel diagnostic methods and treatment modalities for these disorders. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
1K02MH076222-01A1
Application #
7148950
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Meinecke, Douglas L
Project Start
2006-08-01
Project End
2011-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
1
Fiscal Year
2006
Total Cost
$126,846
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Niciu, Mark J; Abdallah, Chadi G; Fenton, Lisa R et al. (2015) A history of early life parental loss or separation is associated with successful cognitive-behavioral therapy in major depressive disorder. J Affect Disord 187:241-4
Abdallah, Chadi G; Jiang, Lihong; De Feyter, Henk M et al. (2014) Glutamate metabolism in major depressive disorder. Am J Psychiatry 171:1320-7
Abdallah, Chadi G; Niciu, Mark J; Fenton, Lisa R et al. (2014) Decreased occipital cortical glutamate levels in response to successful cognitive-behavioral therapy and pharmacotherapy for major depressive disorder. Psychother Psychosom 83:298-307
Krystal, John H; Sanacora, Gerard; Duman, Ronald S (2013) Rapid-acting glutamatergic antidepressants: the path to ketamine and beyond. Biol Psychiatry 73:1133-41
Abdallah, Chadi G; Fasula, Madonna; Kelmendi, Ben et al. (2012) Rapid antidepressant effect of ketamine in the electroconvulsive therapy setting. J ECT 28:157-61
Sanacora, Gerard; Treccani, Giulia; Popoli, Maurizio (2012) Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders. Neuropharmacology 62:63-77
Gomez, Rosane; Behar, Kevin L; Watzl, June et al. (2012) Intravenous ethanol infusion decreases human cortical ?-aminobutyric acid and N-acetylaspartate as measured with proton magnetic resonance spectroscopy at 4 tesla. Biol Psychiatry 71:239-46
Valentine, Gerald W; Mason, Graeme F; Gomez, Rosane et al. (2011) The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [(1)H]-MRS. Psychiatry Res 191:122-7
Banasr, M; Chowdhury, G M I; Terwilliger, R et al. (2010) Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole. Mol Psychiatry 15:501-11
Sanacora, Gerard (2010) Cortical inhibition, gamma-aminobutyric acid, and major depression: there is plenty of smoke but is there fire? Biol Psychiatry 67:397-8

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