Department of Psychiatry Faculty

Graeme F. Mason, Ph.D. Associate Professor of Psychiatry and Diagnostic Radiology Yale Magnetic Resonance Research Center N-141 TAC-MRRC Yale University, School of Medicine 300 Cedar St. New Haven, CT 06520-8043 Tel: 203-737-1478 Fax: 203-785-6643 Email: graeme.mason@yale.edu

Education

1986, B. S., Nuclear Engineering, The Pennsylvania State University
1991, Ph.D., Molecular Biophysics & Biochemistry, Yale University

Research Interest

This group is comprised of biochemists, psychiatrists, and MR physicists working together to study neurotransmitter and energy metabolism in healthy and pathological states. My goal is to understand the relationships between function and neurochemistry in the healthy brain and in neuropsychiatric disorders. To this end, I use non-invasive quantitative magnetic resonance spectroscopy (MRS) and mathematical modeling analyses to measure the concentrations and rates of synthesis of glutamate, glutamine, aspartate, GABA, and other chemicals in the brain. Generally, we apply 1H MRS to measure chemical concentrations under different conditions and develop hypotheses that explain the observations. Those hypotheses are then tested using 13C MRS to measure the rates of synthesis and neurotransmitter release of those compounds in vivo. Recently, using 1H MRS we have discovered that GABA concentrations are reduced by 30-50% in depressed subjects, and our 13C MRS studies show that the reductions are related to lower rates of GABA synthesis and reductions in excitatory glutamate release. Another recent finding is that GABA levels are reduced in the weeks following alcohol detoxification, and we are applying 13C MRS to determine why. We are also applying these techniques to studies of depression, substance abuse, and hormonal effects on the brain. We hope that these approaches will lead to rational selections of pharmacological interventions for a variety of disorders.

Publications of Note

Epperson CN, O'Malley S, Czarkowski KA, Gueorguieva R, Jatlow P, Sanacora G, Rothman DL, Krystal JH, Mason GF (2005) Sex, GABA, and nicotine: the impact of smoking on cortical GABA levels across the menstrual cycle as measured with proton magnetic resonance spectroscopy. Biological Psychiatry 57: 44-48

Mason GF, Petersen KF, de Graaf RA, Kanamatsu T, Otsuki T, Shulman GI, Rothman DL (2003) A comparison of 13C NMR measurements of the rates of glutamine synthesis and the tricarboxylic acid cycle during oral and intravenous administration of [1-13C]glucose. Brain Research Protocols 10: 181-190

Sanacora G, Gueorguieva R, Epperson CN, Wu YT, Appel M, Rothman DL, Krystal JH, Mason GF (2004) Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Archives of General Psychiatry 61: 705-713

Mason GF, Rothman DL (2004) Basic principles of metabolic modeling of NMR (13)C isotopic turnover to determine rates of brain metabolism in vivo. Metabolic Engineering 6: 75-84

Patel AB, de Graaf RA, Mason GF, Rothman DL, Shulman RG, Behar KL (2003) Coupling of glutamatergic neurotransmission and neuronal glucose oxidation over the entire range of cerebral cortex activity. Annals of the New York Academy of Sciences 1003: 452-453

de Graaf RA, Mason GF, Patel AB, Behar KL, Rothman DL (2003) In vivo 1H-[13C]-NMR spectroscopy of cerebral metabolism. NMR in Biomedicine 16: 339-357

Mason GF, Martin DL, Martin SB, Manor D, Sibson NR, Patel A, Rothman DL, Behar KL (2001) Decrease in GABA synthesis rate in rat cortex following vigabatrin administration correlates with the decrease in GAD67 protein. Brain Research 914: 81-91

Sanacora G, Mason GF, Rothman DL, Behar KL, Petroff OAC, Berman RM, Krystal JH (1999) Preliminary evidence of reduced cortical GABA levels in depressed patients assessed using 1H-magnetic resonance spectroscopy. Archives of General Psychiatry 56: 1043-1047

Links

Center for the Translational Neuroscience of Alcoholism

Yale Magnetic Resonance Center for Research in Metabolism & Physiology

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