Independent Scientist Award-KO2: As Co-Director of an Alcoholism Research Center, I have supported my salary since 1991. In July, 1998, the VA will terminate this national program. At that time, I will assume substantial clinical responsibilities unless I find an alternative mechanism to support my salary. This K02 Award would enable me to sustain my research and develop further expertise in areas critical to my research program. My research has focussed on characterizing the clinical significance of glutamate and GABA dysregulation in alcoholism. With NIAAA support, I conducted a study that indicated that the NMDA antagonist, ketamine, had ethanol-like effects and altered reward valence in alcoholic patients. These patients showed blunted dysphoric responses and increased euphoric responses. Thus, NMDA receptor dysregulation may alter the NMDA antagonist component of ethanol response in patients in a manner that promotes relapse. To build towards pharmacotherapy, I have proposed to compare responses to a partial agonist of the strychnine-insensitive glycine (SIGLY) site of the NMDA receptor in recently detoxified alcoholics and controls (Years 1-3) and to determine whether drugs acting at this site modulate ethanol cue-induced craving in patients (Years 4-5). To facilitate these objectives, I will pursue additional training in multivariate statistics and I will work collaboratively to develop methods for assessing craving that are independent of self-report and would be applied to studies in Years 4-5. My other major research focus has been the study of reductions in GABA function in alcoholics using 133I iomazenil single photon emission computerized tomography (SPECT) and magnetic resonance spectroscopy (lH-NMR). Respectively, these techniques measure benzodiazepine/GABA-A receptor density and GABA levels. I have proposed a study that employs both SPECT and 1H-NMR in a longitudinal assessment of the recovery of GABA systems with sobriety. If funded, this study would cover years 1-4 of this K02 period. In year 5, I propose to characterize the activity of the GABA synthetic enzyme, glutamic acid decarboxylase, in alcoholic patients using a 13C-glucose infusion technique. In this work, I focus my career development on gaining further expertise in 1H- and 13C-NMR. As a result, I have developed an educational program designed to facilitate my development in these areas. In summary, this K02 award would foster my academic development and enable me to better contribute to the building of pathophysiologic models of alcoholism that can guide medications development for this disorder.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Scientist Development Award - Research (K02)
Project #
Application #
Study Section
Special Emphasis Panel (ZAA1-FF (02))
Program Officer
Witt, Ellen
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Yale University
Schools of Medicine
New Haven
United States
Zip Code
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
D'Souza, Deepak Cyril; Gil, Roberto B; Zuzarte, Edward et al. (2006) gamma-Aminobutyric acid-serotonin interactions in healthy men: implications for network models of psychosis and dissociation. Biol Psychiatry 59:128-37
Morgan, Celia J A; Perry, Edward B; Cho, Hyung-Sang et al. (2006) Greater vulnerability to the amnestic effects of ketamine in males. Psychopharmacology (Berl) 187:405-14
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
Hoffman, Ralph E; Gueorguieva, Ralitza; Hawkins, Keith A et al. (2005) Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and moderators in a fifty patient sample. Biol Psychiatry 58:97-104
D'Souza, Deepak Cyril; Abi-Saab, Walid Michel; Madonick, Steven et al. (2005) Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biol Psychiatry 57:594-608
Gueorguieva, Ralitza; Krystal, John H (2004) Move over ANOVA: progress in analyzing repeated-measures data and its reflection in papers published in the Archives of General Psychiatry. Arch Gen Psychiatry 61:310-7
D'Souza, Deepak Cyril; Perry, Edward; MacDougall, Lisa et al. (2004) The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology 29:1558-72
Lappalainen, J; Kranzler, H R; Petrakis, I et al. (2004) Confirmation and fine mapping of the chromosome 1 alcohol dependence risk locus. Mol Psychiatry 9:312-9
Petrakis, Ismene L; Limoncelli, Diana; Gueorguieva, Ralitza et al. (2004) Altered NMDA glutamate receptor antagonist response in individuals with a family vulnerability to alcoholism. Am J Psychiatry 161:1776-82

Showing the most recent 10 out of 39 publications