Alcoholic Intoxication; Alcoholism; Amino Acids; Carbohydrates; Central Nervous System Diseases; Fatty Acids; Mathematical Computing; Substance Withdrawal Syndrome; Tobacco Use Disorder; Mood Disorders; Cocaine-Related Disorders; Alcohol-Induced Disorders, Nervous System; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Neuroimaging
Public Health Interests
Alcoholism/Alcohol; Depression; Metabolism; Modeling
Psychiatry: Center for Nicotine and Tobacco Use Research at Yale (CENTURY) | Center for the Translational Neuroscience of Alcoholism | Neurocognition, Neurocomputation, and Neurogenetics, Division of | Neuroscience Research Training Program (NRTP) | Obsessive Compulsive Disorder Research Clinic
Dr. Mason's research program is focused on the development and evaluation of quantitative hypotheses of brain energy utilization, neurotransmitter metabolism, and function, as well as their application to neuropsychiatric disorders. Dr. Mason's primary methodologies are 1H and 13C magnetic resonance spectroscopy and mathematical modeling of metabolism and enzyme kinetics, and the effects of nicotine and ethanol on GABA, glutamate, and energy metabolism form a primary research focus for his program.
MRS uses technology that is similar to that of standard MRI, but the results are measurements of chemicals instead of images. The chemical measurements are used to measure the effects of variability in function, disease, and pharmacology on the concentrations of brain glutamate, glutamine, GABA and other compounds that are important for brain activity.
Among the most unique capacities of this laboratory is the ability to use MRS to measure metabolic rates with the stable isotope 13C. It is possible to observe the synthesis of glutamate, glutamine, GABA, and other compounds in the intact brain, with collaborative studies to examine other systems. Measurements of the synthesis of these compounds provide an assessment of neurotransmission and energetics in the brain. To plan experiments and evaluate data, mathematical simulations of brain metabolism are used with a user-friendly package called CWave. As theories are developed, new experiments planned, and new data obtained, the models are constantly under revision and expansion.
The goals of the laboratory are to acquire the necessary data and create concrete mathematical expressions of the metabolic regulation of brain metabolism. Such expressions will help understand basic biochemical regulation, aid the development and evaluation of pharmacologic agents, and predict the effects of functional perturbations on the health and activity of the human brain.
Extensive Research Description
Dr. Mason's research integrates quantitative approaches to measure functional brain chemistry and the study of neuropsychiatric disorders. The primary methods used are 1H and 13C magnetic resonance spectroscopy, with some studies using mass spectrometry, as well as the mathematical assessment of metabolism. Current areas of research include alcohol effects, depression, manic-depressive disorder, alcoholism, panic disorder, premenstrual syndrome, and obsessive-compulsive disorder. His primary areas of interest are the effects of alcohol on the brain, and to that end, his research evaluates acute and chronic effects of alcohol on the brain, from the perspectives of neurotransmission, metabolism, adaptation, and vulnerability to dependence.
Integrated, step-wise, mass-isotopomeric flux analysis of the TCA Cycle.
Alves TC, Pongratz RL, Zhao X, Yarborough O, Sereda S, Shirihai O, Cline GW, Mason GF, Kibbey RG (2015) Integrated, step-wise, mass-isotopomeric flux analysis of the TCA Cycle. Cell Metab (in press)
Glutamate metabolism in major depressive disorder.
Abdallah CG, Jiang L, De Feyter HM, Fasula MK, Krystal JH, Rothman DL, Mason GF, Sanacora G (2014) Glutamate Metabolism in Major Depressive Disorder. Amer J Psychiatry 171:1320-1327
Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure.
Wang J, Du H, Jiang L, Ma X, de Graaf R, Behar K, Mason GF (2013) Oxidation and Effects of Ethanol in the Rat Brain after Chronic Ethanol Exposure. Proc Natl Acad Sci USA 110: 14444-14449
- Exposure to antecedent recurrent hypoglycemia increases lactate uptake under hypoglycemia, supporting TCA cycle activity and neuronal function. Jiang L, Herzog RI, Herman P, Ganganna B, Mason GF, Hyder F, Rothman D, Sherwin R, Behar KL (2013) J Clin Inv 123: 1605-1614
Intravenous ethanol infusion decreases human cortical GABA and NAA as measured with 1H-MRS at 4T
Gomez R, Behar KL, Watzl J, Weinzimer SA, Gulanski B, Sanacora G, Koretski J, Guidone E, Jiang L, Petrakis IL, Pittman B3, Krystal JH, Mason GF (2012) Intravenous ethanol infusion decreases human cortical GABA and NAA as measured with 1H-MRS at 4T. Biol
Evaluation of cerebral acetate transport and utilization rates in the anesthetized rat in vivo using 1H-[13C]NMR and [2-13C]acetate.
Patel AB, de Graaf RA, Rothman DL, Behar KL, Mason GF (2010) Evaluation of cerebral acetate transport and utilization rates in the anesthetized rat in vivo using 1H-[13C]NMR and [2-13C]acetate. J Cereb Blood Flow Metab 30: 1200-1213
Regional metabolite levels and turnover in the awake rat brain under the influence of nicotine.
Wang J, Jiang L, Jiang F, Ma X, Chowdhury GMI, Mason G (2010) Regional metabolite levels and turnover in the awake rat brain under the influence of nicotine. J Neurochem 113: 1447-1458
- Boumezbeur F, Mason GF, de Graaf RA, Behar KL, Cline GW, Shulman GI, Rothman DL, Petersen DL (2010) Alterations in brain mitochondrial metabolism associated with aging in humans. J Cereb Blood Flow Metab 30: 211-221
Measurements of the anaplerotic rate in the human cerebral cortex using 13C MRS and [1-13C] and [2-13C]glucose.
Mason GF, Petersen KF, de Graaf RA, Shulman GI, Rothman DL (2007) Measurements of the anaplerotic rate in the human cerebral cortex using 13C MRS and [1-13C] and [2-13C]glucose. J Neurochem 100: 73-86.
Increased Brain Monocarboxylic Acid Transport and Utilization in Type 1 Diabetes.
Mason GF, Petersen KF, Lebon V, Rothman DL, Shulman GI (2006) Increased Brain Monocarboxylic Acid Transport and Utilization in Type 1 Diabetes. Diabetes 55: 929-934.
Full List of PubMed Publications
- Prinsen H, de Graaf RA, Mason GF, Pelletier D, Juchem C: Reproducibility measurement of glutathione, GABA, and glutamate: Towards in vivo neurochemical profiling of multiple sclerosis with MR spectroscopy at 7T. J Magn Reson Imaging. 2017 Jan; 2016 Jun 28. PMID: 27351712
- Krystal JH, Abi-Dargham A, Akbarian S, Arnsten AFT, Barch DM, Bearden CE, Braff DL, Brown ES, Bullmore ET, Carlezon WA Jr, Carter CS, Cook EH Jr, Daskalakis ZJ, DiLeone RJ, Duman RS, Grace AA, Hariri AR, Harrison PJ, Hiroi N, Kenny PJ, Kleinman JE, Krystal AD, Lewis DA, Lipska BK, Marder SR, Mason GF, Mathalon DH, McClung CA, McDougle CJ, McIntosh AM, McMahon FJ, Mirnics K, Monteggia LM, Narendran R, Nestler EJ, Neumeister A, O'Donovan MC, Öngür D, Pariante CM, Paulus MP, Pearlson G, Phillips ML, Pine DS, Pizzagalli DA, Pletnikov MV, Ragland JD, Rapoport JL, Ressler KJ, Russo SJ, Sanacora G, Sawa A, Schatzberg AF, Shaham Y, Shamay-Tsoory SG, Sklar P, State MW, Stein MB, Strakowski SM, Taylor SF, Turecki G, Turetsky BI, Weissman MM, Zachariou V, Zarate CA Jr, Zubieta JK: Constance E. Lieber, Theodore R. Stanley, and the Enduring Impact of Philanthropy on Psychiatry Research. Biol Psychiatry. 2016 Jul 15. PMID: 27346079
- Hillmer AT, Mason GF, Fucito LM, O'Malley SS, Cosgrove KP: How Imaging Glutamate, γ-Aminobutyric Acid, and Dopamine Can Inform the Clinical Treatment of Alcohol Dependence and Withdrawal. Alcohol Clin Exp Res. 2015 Dec; 2015 Oct 28. PMID: 26510169
- Abdallah CG, Jiang L, De Feyter HM, Fasula M, Krystal JH, Rothman DL, Mason GF, Sanacora G: Glutamate metabolism in major depressive disorder. Am J Psychiatry. 2014 Dec 1; 2014 Oct 31. PMID: 25073688
- Bagga P, Behar KL, Mason GF, De Feyter HM, Rothman DL, Patel AB: Characterization of cerebral glutamine uptake from blood in the mouse brain: implications for metabolic modeling of 13C NMR data. J Cereb Blood Flow Metab. 2014 Oct; 2014 Jul 30. PMID: 25074745
- Pugh KR, Frost SJ, Rothman DL, Hoeft F, Del Tufo SN, Mason GF, Molfese PJ, Mencl WE, Grigorenko EL, Landi N, Preston JL, Jacobsen L, Seidenberg MS, Fulbright RK: Glutamate and choline levels predict individual differences in reading ability in emergent readers. J Neurosci. 2014 Mar 12. PMID: 24623786
- Niciu MJ, Mason GF: Neuroimaging in Alcohol and Drug Dependence. Curr Behav Neurosci Rep. 2014 Mar 1. PMID: 24678450
- Abdallah CG, Niciu MJ, Fenton LR, Fasula MK, Jiang L, Black A, Rothman DL, Mason GF, Sanacora G: Decreased occipital cortical glutamate levels in response to successful cognitive-behavioral therapy and pharmacotherapy for major depressive disorder. Psychother Psychosom. 2014; 2014 Aug 6. PMID: 25116726
- Solecki W, Wickham RJ, Behrens S, Wang J, Zwerling B, Mason GF, Addy NA: Differential role of ventral tegmental area acetylcholine and N-methyl-D-aspartate receptors in cocaine-seeking. Neuropharmacology. 2013 Dec; 2013 Jul 11. PMID: 23850572
- Wang J, Du H, Ma X, Pittman B, Castracane L, Li TK, Behar KL, Mason GF: Metabolic products of [2-(13) C]ethanol in the rat brain after chronic ethanol exposure. J Neurochem. 2013 Nov; 2013 Sep 23. PMID: 24033360
- De Feyter HM, Mason GF, Shulman GI, Rothman DL, Petersen KF: Increased brain lactate concentrations without increased lactate oxidation during hypoglycemia in type 1 diabetic individuals. Diabetes. 2013 Sep; 2013 May 28. PMID: 23715622
- Gulanski BI, De Feyter HM, Page KA, Belfort-DeAguiar R, Mason GF, Rothman DL, Sherwin RS: Increased brain transport and metabolism of acetate in hypoglycemia unawareness. J Clin Endocrinol Metab. 2013 Sep; 2013 Jun 24. PMID: 23796565
- Herzog RI, Jiang L, Herman P, Zhao C, Sanganahalli BG, Mason GF, Hyder F, Rothman DL, Sherwin RS, Behar KL: Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia. J Clin Invest. 2013 May; 2013 Apr 1. PMID: 23543056
- Jiang L, Gulanski BI, De Feyter HM, Weinzimer SA, Pittman B, Guidone E, Koretski J, Harman S, Petrakis IL, Krystal JH, Mason GF: Increased brain uptake and oxidation of acetate in heavy drinkers. J Clin Invest. 2013 Apr; 2013 Mar 8. PMID: 23478412
- Morgan PT, Pace-Schott EF, Mason GF, Forselius E, Fasula M, Valentine GW, Sanacora G: Cortical GABA levels in primary insomnia. Sleep. 2012 Jun 1; 2012 Jun 1. PMID: 22654200
- Jiang L, Mason GF, Rothman DL, de Graaf RA, Behar KL: Cortical substrate oxidation during hyperketonemia in the fasted anesthetized rat in vivo. J Cereb Blood Flow Metab. 2011 Dec; 2011 Jul 6. PMID: 21731032
- Rothman DL, De Feyter HM, de Graaf RA, Mason GF, Behar KL: 13C MRS studies of neuroenergetics and neurotransmitter cycling in humans. NMR Biomed. 2011 Oct; 2011 Aug 31. PMID: 21882281
- Cosgrove KP, Esterlis I, Mason GF, Bois F, O'Malley SS, Krystal JH: Neuroimaging insights into the role of cortical GABA systems and the influence of nicotine on the recovery from alcohol dependence. Neuropharmacology. 2011 Jun; 2011 Jan 27. PMID: 21276806
- Valentine GW, Mason GF, Gomez R, Fasula M, Watzl J, Pittman B, Krystal JH, Sanacora G: The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [(1)H]-MRS. Psychiatry Res. 2011 Feb 28; 2011 Jan 12. PMID: 21232924
- Palejev D, Hwang W, Landi N, Eastman M, Frost SJ, Fulbright RK, Kidd JR, Kidd KK, Mason GF, Mencl WE, Yrigollen C, Pugh KR, Grigorenko EL: An application of the elastic net for an endophenotype analysis. Behav Genet. 2011 Jan; 2011 Jan 13. PMID: 21229297
- Boumezbeur F, Petersen KF, Cline GW, Mason GF, Behar KL, Shulman GI, Rothman DL: The contribution of blood lactate to brain energy metabolism in humans measured by dynamic 13C nuclear magnetic resonance spectroscopy. J Neurosci. 2010 Oct 20. PMID: 20962220
- Patel AB, de Graaf RA, Rothman DL, Behar KL, Mason GF: Evaluation of cerebral acetate transport and metabolic rates in the rat brain in vivo using 1H-[13C]-NMR. J Cereb Blood Flow Metab. 2010 Jun; 2010 Feb 3. PMID: 20125180
- Wang J, Jiang L, Jiang Y, Ma X, Chowdhury GM, Mason GF: Regional metabolite levels and turnover in the awake rat brain under the influence of nicotine. J Neurochem. 2010 Jun; 2010 Mar 14. PMID: 20345764
- Boumezbeur F, Mason GF, de Graaf RA, Behar KL, Cline GW, Shulman GI, Rothman DL, Petersen KF: Altered brain mitochondrial metabolism in healthy aging as assessed by in vivo magnetic resonance spectroscopy. J Cereb Blood Flow Metab. 2010 Jan; 2009 Sep 30. PMID: 19794401
- Jiang L, Herzog RI, Mason GF, de Graaf RA, Rothman DL, Sherwin RS, Behar KL: Recurrent antecedent hypoglycemia alters neuronal oxidative metabolism in vivo. Diabetes. 2009 Jun; 2009 Mar 10. PMID: 19276443
- Befroy DE, Petersen KF, Dufour S, Mason GF, Rothman DL, Shulman GI: Increased substrate oxidation and mitochondrial uncoupling in skeletal muscle of endurance-trained individuals. Proc Natl Acad Sci U S A. 2008 Oct 28; 2008 Oct 20. PMID: 18936488
- Krystal JH, Carter CS, Geschwind D, Manji HK, March JS, Nestler EJ, Zubieta JK, Charney DS, Goldman D, Gur RE, Lieberman JA, Roy-Byrne P, Rubinow DR, Anderson SA, Barondes S, Berman KF, Blair J, Braff DL, Brown ES, Calabrese JR, Carlezon WA Jr, Cook EH Jr, Davidson RJ, Davis M, Desimone R, Drevets WC, Duman RS, Essock SM, Faraone SV, Freedman R, Friston KJ, Gelernter J, Geller B, Gill M, Gould E, Grace AA, Grillon C, Gueorguieva R, Hariri AR, Innis RB, Jones EG, Kleinman JE, Koob GF, Krystal AD, Leibenluft E, Levinson DF, Levitt PR, Lewis DA, Liberzon I, Lipska BK, Marder SR, Markou A, Mason GF, McDougle CJ, McEwen BS, McMahon FJ, Meaney MJ, Meltzer HY, Merikangas KR, Meyer-Lindenberg A, Mirnics K, Monteggia LM, Neumeister A, O'Brien CP, Owen MJ, Pine DS, Rapoport JL, Rauch SL, Robbins TW, Rosenbaum JF, Rosenberg DR, Ross CA, Rush AJ, Sackeim HA, Sanacora G, Schatzberg AF, Shaham Y, Siever LJ, Sunderland T, Tecott LH, Thase ME, Todd RD, Weissman MM, Yehuda R, Yoshikawa T, Young EA, McCandless R: It is time to take a stand for medical research and against terrorism targeting medical scientists. Biol Psychiatry. 2008 Apr 15. PMID: 18371494
- Chowdhury GM, Patel AB, Mason GF, Rothman DL, Behar KL: Glutamatergic and GABAergic neurotransmitter cycling and energy metabolism in rat cerebral cortex during postnatal development. J Cereb Blood Flow Metab. 2007 Dec; 2007 Apr 18. PMID: 17440492
- Befroy DE, Petersen KF, Dufour S, Mason GF, de Graaf RA, Rothman DL, Shulman GI: Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients. Diabetes. 2007 May; 2007 Feb 7. PMID: 17287462
- Mason GF: Get sober; stay sober. Brain. 2007 Jan. PMID: 17178741
- Mason GF, Petersen KF, de Graaf RA, Shulman GI, Rothman DL: Measurements of the anaplerotic rate in the human cerebral cortex using 13C magnetic resonance spectroscopy and [1-13C] and [2-13C] glucose. J Neurochem. 2007 Jan; 2006 Oct 31. PMID: 17076763
- Mason GF, Krystal JH: MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases. NMR Biomed. 2006 Oct. PMID: 16986118
- Amin Z, Mason GF, Cavus I, Krystal JH, Rothman DL, Epperson CN: The interaction of neuroactive steroids and GABA in the development of neuropsychiatric disorders in women. Pharmacol Biochem Behav. 2006 Aug; 2006 Jul 24. PMID: 16860856
- Epperson CN, Gueorguieva R, Czarkowski KA, Stiklus S, Sellers E, Krystal JH, Rothman DL, Mason GF: Preliminary evidence of reduced occipital GABA concentrations in puerperal women: a 1H-MRS study. Psychopharmacology (Berl). 2006 Jun; 2006 May 3. PMID: 16724188
- Mason GF, Petersen KF, Lebon V, Rothman DL, Shulman GI: Increased brain monocarboxylic acid transport and utilization in type 1 diabetes. Diabetes. 2006 Apr. PMID: 16567513
- Sanacora G, Fenton LR, Fasula MK, Rothman DL, Levin Y, Krystal JH, Mason GF: Cortical gamma-aminobutyric acid concentrations in depressed patients receiving cognitive behavioral therapy. Biol Psychiatry. 2006 Feb 1; 2005 Sep 1. PMID: 16139814
- Mason GF, Petrakis IL, de Graaf RA, Gueorguieva R, Guidone E, Coric V, Epperson CN, Rothman DL, Krystal JH: Cortical gamma-aminobutyric acid levels and the recovery from ethanol dependence: preliminary evidence of modification by cigarette smoking. Biol Psychiatry. 2006 Jan 1; 2005 Nov 14. PMID: 16289397
- Patel AB, de Graaf RA, Mason GF, Rothman DL, Shulman RG, Behar KL: The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo. Proc Natl Acad Sci U S A. 2005 Apr 12; 2005 Apr 4. PMID: 15809416
- Epperson CN, O'Malley S, Czarkowski KA, Gueorguieva R, Jatlow P, Sanacora G, Rothman DL, Krystal JH, Mason GF: 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. 2005 Jan 1. PMID: 15607299
- Patel AB, de Graaf RA, Mason GF, Kanamatsu T, Rothman DL, Shulman RG, Behar KL: Glutamatergic neurotransmission and neuronal glucose oxidation are coupled during intense neuronal activation. J Cereb Blood Flow Metab. 2004 Sep. PMID: 15356418
- de Graaf RA, Mason GF, Patel AB, Rothman DL, Behar KL: Regional glucose metabolism and glutamatergic neurotransmission in rat brain in vivo. Proc Natl Acad Sci U S A. 2004 Aug 24; 2004 Aug 13. PMID: 15310848
- Sanacora G, Gueorguieva R, Epperson CN, Wu YT, Appel M, Rothman DL, Krystal JH, Mason GF: Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry. 2004 Jul. PMID: 15237082
- Mason GF, Rothman DL: Basic principles of metabolic modeling of NMR (13)C isotopic turnover to determine rates of brain metabolism in vivo. Metab Eng. 2004 Jan. PMID: 14734257
- Patel AB, De Graaf RA, Mason GF, Rothman DL, Shulman RG, Behar KL: Coupling of glutamatergic neurotransmission and neuronal glucose oxidation over the entire range of cerebral cortex activity. Ann N Y Acad Sci. 2003 Nov. PMID: 14684486
- Kugaya A, Sanacora G, Verhoeff NP, Fujita M, Mason GF, Seneca NM, Bozkurt A, Khan SA, Anand A, Degen K, Charney DS, Zoghbi SS, Baldwin RM, Seibyl JP, Innis RB: Cerebral benzodiazepine receptors in depressed patients measured with [123I]iomazenil SPECT. Biol Psychiatry. 2003 Oct 15. PMID: 14550678
- de Graaf RA, Mason GF, Patel AB, Behar KL, Rothman DL: In vivo 1H-[13C]-NMR spectroscopy of cerebral metabolism. NMR Biomed. 2003 Oct-Nov. PMID: 14679499
- Mason GF: Magnetic resonance spectroscopy for studies of neurotransmission in vivo. Psychopharmacol Bull. 2003 Spring. PMID: 14566212
- Sanacora G, Mason GF, Rothman DL, Hyder F, Ciarcia JJ, Ostroff RB, Berman RM, Krystal JH: Increased cortical GABA concentrations in depressed patients receiving ECT. Am J Psychiatry. 2003 Mar. PMID: 12611844
- Mason GF, Falk Petersen K, de Graaf RA, Kanamatsu T, Otsuki T, Shulman GI, Rothman DL: A comparison of (13)C NMR measurements of the rates of glutamine synthesis and the tricarboxylic acid cycle during oral and intravenous administration of [1-(13)C]glucose. Brain Res Brain Res Protoc. 2003 Feb. PMID: 12565689
- de Graaf RA, Brown PB, Mason GF, Rothman DL, Behar KL: Detection of [1,6-13C2]-glucose metabolism in rat brain by in vivo 1H-[13C]-NMR spectroscopy. Magn Reson Med. 2003 Jan. PMID: 12509818
- Epperson CN, Haga K, Mason GF, Sellers E, Gueorguieva R, Zhang W, Weiss E, Rothman DL, Krystal JH: Cortical gamma-aminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder: a proton magnetic resonance spectroscopy study. Arch Gen Psychiatry. 2002 Sep. PMID: 12215085
- Mason GF, Rothman DL: Graded image segmentation of brain tissue in the presence of inhomogeneous radio frequency fields. Magn Reson Imaging. 2002 Jun. PMID: 12206869
- Sanacora G, Mason GF, Rothman DL, Krystal JH: Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. Am J Psychiatry. 2002 Apr. PMID: 11925309
- Lebon V, Petersen KF, Cline GW, Shen J, Mason GF, Dufour S, Behar KL, Shulman GI, Rothman DL: Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. J Neurosci. 2002 Mar 1. PMID: 11880482