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MR Spectroscopic Studies of the Brain in Psychiatric Disorders

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Brain Imaging in Behavioral Neuroscience

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 11))

Abstract

The measurement of brain metabolites with magnetic resonance spectroscopy (MRS) provides a unique perspective on the brain bases of neuropsychiatric disorders. As a context for interpreting MRS studies of neuropsychiatric disorders, we review the characteristic MRS signals, the metabolic dynamics, and the neurobiological significance of the major brain metabolites that can be measured using clinical MRS systems. These metabolites include N-acetylaspartate (NAA), creatine, choline-containing compounds, myo-inositol, glutamate and glutamine, lactate, and gamma-amino butyric acid (GABA). For the major adult neuropsychiatric disorders (schizophrenia, bipolar disorder, major depression, and the anxiety disorders), we highlight the most consistent MRS findings, with an emphasis on those with potential clinical or translational significance. Reduced NAA in specific brain regions in schizophrenia, bipolar disorder, post-traumatic stress disorder, and obsessive–compulsive disorder corroborate findings of reduced brain volumes in the same regions. Future MRS studies may help determine the extent to which the neuronal dysfunction suggested by these findings is reversible in these disorders. Elevated glutamate and glutamine (Glx) in patients with bipolar disorder and reduced Glx in patients with unipolar major depression support models of increased and decreased glutamatergic function, respectively, in those conditions. Reduced phosphomonoesters and intracellular pH in bipolar disorder and elevated dynamic lactate responses in panic disorder are consistent with metabolic models of pathogenesis in those disorders. Preliminary findings of an increased glutamine/glutamate ratio and decreased GABA in patients with schizophrenia are consistent with a model of NMDA hypofunction in that disorder. As MRS methods continue to improve, future studies may further advance our understanding of the natural history of psychiatric illnesses, improve our ability to test translational models of pathogenesis, clarify therapeutic mechanisms of action, and allow clinical monitoring of the effects of interventions on brain metabolic markers.

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Abbreviations

1H-MRS:

Proton magnetic resonance spectroscopy

2D:

Two dimensional

31P-MRS:

Phosphorous magnetic resonance spectroscopy

ADP:

Adenosine diphosphate

AGAT:

Arginine-glycine aminotransferase

ASICs:

Acid sensing ion channels

ASPA:

Aspartoacylase

Asp-NAT:

Aspartate N-acetyltransferase

ATP:

Adenosine triphosphate

CK:

Creatine kinase

CNS:

Central nervous system

CO2:

Carbon dioxide

CSF:

Cerebrospinal fluid

CSI:

Chemical shift imaging

EAAT1:

Excitatory amino acid transporter 1

EAAT2:

Excitatory amino acid transporter 2

ECF:

Extracellular fluid

EEG:

Electroencephalogram

GAA:

Guanidinoacetate

GABA:

Gamma aminobutyric acid

GABA-T:

Gamma aminobutyric acid transaminase

GAD:

Glutamic acid decarboxylase

GAD65:

65 kilodalton form of GAD

GAD67:

67 kilodalton form of GAD

GAMT:

Guanidinoacetate methyltransferase

GAT:

GABA transporter

Glx:

The combined signal from glutamate and glutamine

GPCho:

Glycerophosphorylcholine

H+:

Hydrogen ions

Hz:

Hertz, or cycles per second

Km:

Michaelis-Menten constant

MCT:

Monocarboxylate transporter

MEGA:

Mescher-Garwood

mM:

Millimoles

MR:

Magnetic resonance

MRI:

Magnetic resonance imaging

mRNA:

Messenger ribonucleic acid

MRS:

Magnetic resonance spectroscopy

MRSI:

Magnetic resonance spectroscopic imaging

MRUI:

Magnetic Resonance User Interface

ms:

Milliseconds

NAA:

N-acetylaspartate

NAAG:

N-acetylaspartylglutamate

NMDA:

N-methyl-D-aspartic acid

OCD:

Obsessive compulsive disorder

PCho:

Phosphorylcholine

PEPSI:

Proton echoplanar spectroscopic imaging

pH:

Negative logarithm of hydrogen ion concentration

PMEs:

Phosphomonoesters

ppm:

Parts per million

PRESS:

Point resolved spectroscopic sequence

PTSD:

Post traumatic stress disorder

SSRI:

Selective serotonin reuptake inhibitor

TCA:

Tricarboxylic acid

TE:

Echo time

VGluT:

Vesicular glutamate transporter

References

  • Abbott C, Bustillo J (2006) What have we learned from proton magnetic resonance spectroscopy about schizophrenia? A critical update. Curr Opin Psychiatry 19:135–139

    PubMed  Google Scholar 

  • Ajilore O, Haroon E, Kumaran S et al (2007) Measurement of brain metabolites in patients with type 2 diabetes and major depression using proton magnetic resonance spectroscopy. Neuropsychopharmacology 32:1224–1231

    CAS  PubMed  Google Scholar 

  • Albrecht J, Sonnewald U, Waagepetersen HS, Schousboe A (2007) Glutamine in the central nervous system: function and dysfunction. Front Biosci 12:332–343

    CAS  PubMed  Google Scholar 

  • Almeida LS, Salomons GS, Hogenboom F, Jakobs C, Schoffelmeer AN (2006) Exocytotic release of creatine in rat brain. Synapse 60:118–123

    CAS  PubMed  Google Scholar 

  • Andres RH, Ducray AD, Schlattner U, Wallimann T, Widmer HR (2008) Functions and effects of creatine in the central nervous system. Brain Res Bull 76:329–343

    CAS  PubMed  Google Scholar 

  • Arckens L, Schweigart G, Qu Y et al (2000) Cooperative changes in GABA, glutamate and activity levels: the missing link in cortical plasticity. Eur J Neurosci 12:4222–4232

    CAS  PubMed  Google Scholar 

  • Ariyannur PS, Moffett JR, Manickam P et al (2010) Methamphetamine-induced neuronal protein NAT8L is the NAA biosynthetic enzyme: implications for specialized acetyl coenzyme A metabolism in the CNS. Brain Res 1335:1–13

    CAS  PubMed  Google Scholar 

  • Arnone D, Cavanagh J, Gerber D, Lawrie SM, Ebmeier KP, McIntosh AM (2009) Magnetic resonance imaging studies in bipolar disorder and schizophrenia: meta-analysis. Br J Psychiatry 195:194–201

    PubMed  Google Scholar 

  • Atmaca M, Yildirim H, Ozdemir H, Ogur E, Tezcan E (2007) Hippocampal 1H MRS in patients with bipolar disorder taking valproate versus valproate plus quetiapine. Psychol Med 37:121–129

    PubMed  Google Scholar 

  • Baslow MH (2007) N-acetylaspartate and N-acetylaspartylglutamate. In: Lajtha A, Oja S, Schousboe A, Saransaari P (eds) Handbook of neurochemistry and molecular neurobiology: amino acids and peptides in the nervous system. Springer, New York, pp 305–346

    Google Scholar 

  • Bates TE, Strangward M, Keelan J, Davey GP, Munro PM, Clark JB (1996) Inhibition of N-acetylaspartate production: implications for 1H MRS studies in vivo. Neuroreport 7:1397–1400

    CAS  PubMed  Google Scholar 

  • Beard E, Braissant O (2010) Synthesis and transport of creatine in the CNS: importance for cerebral functions. J Neurochem 115:297–313

    CAS  PubMed  Google Scholar 

  • Bergersen LH (2007) Is lactate food for neurons? Comparison of monocarboxylate transporter subtypes in brain and muscle. Neuroscience 145:11–19

    CAS  PubMed  Google Scholar 

  • Berridge MJ (1989) The Albert Lasker medical awards: inositol trisphosphate, calcium, lithium, and cell signaling. JAMA 262:1834–1841

    CAS  PubMed  Google Scholar 

  • Bertolino A, Callicott JH, Mattay VS, Weidenhammer KM, Rakow R, Egan MF, Weinberger DR (2001) The effect of treatment with antipsychotic drugs on brain N-acetylaspartate measures in patients with schizophrenia. Biol Psychiatry 49:39–46

    CAS  PubMed  Google Scholar 

  • Bertolino A, Frye M, Callicott JH et al (2003) Neuronal pathology in the hippocampal area of patients with bipolar disorder: a study with proton magnetic resonance spectroscopic imaging. Biol Psychiatry 53:906–913

    PubMed  Google Scholar 

  • Bhagwagar Z, Wylezinska M, Taylor M, Jezzard P, Matthews PM, Cowen PJ (2004) Increased brain GABA concentrations following acute administration of a selective serotonin reuptake inhibitor. Am J Psychiatry 161:368–370

    PubMed  Google Scholar 

  • Bhagwagar Z, Wylezinska M, Jezzard P et al (2007) Reduction in occipital cortex gamma-aminobutyric acid concentrations in medication-free recovered unipolar depressed and bipolar subjects. Biol Psychiatry 61:806–812

    CAS  PubMed  Google Scholar 

  • Bhakoo KK, Williams IT, Williams SR, Gadian DG, Noble MD (1996) Proton nuclear magnetic resonance spectroscopy of primary cells derived from nervous tissue. J Neurochem 66:1254–1263

    CAS  PubMed  Google Scholar 

  • Binesh N, Kumar A, Hwang S, Mintz J, Thomas MA (2004) Neurochemistry of late-life major depression: a pilot two-dimensional MR spectroscopic study. J Magn Reson Imaging 20:1039–1045

    PubMed  Google Scholar 

  • Bitsch A, Bruhn H, Vougioukas V, Stringaris A, Lassmann H, Frahm J, Bruck W (1999) Inflammatory CNS demyelination: histopathologic correlation with in vivo quantitative proton MR spectroscopy. Am J Neuroradiol 20:1619–1627

    CAS  PubMed  Google Scholar 

  • Bitto E, Bingman CA, Wesenberg GE, McCoy JG, Phillips GN Jr (2007) Structure of aspartoacylase, the brain enzyme impaired in Canavan disease. Proc Natl Acad Sci U S A 104:456–461

    CAS  PubMed  Google Scholar 

  • Bora E, Fornito A, Yucel M, Pantelis C (2010) Voxelwise meta-analysis of gray matter abnormalities in bipolar disorder. Biol Psychiatry 67:1097–1105

    PubMed  Google Scholar 

  • Boulanger Y, Labelle M, Khiat A (2000) Role of phospholipase A(2) on the variations of the choline signal intensity observed by 1H magnetic resonance spectroscopy in brain diseases. Brain Res Brain Res Rev 33:380–389

    CAS  PubMed  Google Scholar 

  • Braissant O, Beard E, Torrent C, Henry H (2010) Dissociation of AGAT, GAMT and SLC6A8 in CNS: relevance to creatine deficiency syndromes. Neurobiol Dis 37:423–433

    CAS  PubMed  Google Scholar 

  • Brambilla P, Stanley JA, Sassi RB, Nicoletti MA, Mallinger AG, Keshavan MS, Soares JC (2004) 1H MRS study of dorsolateral prefrontal cortex in healthy individuals before and after lithium administration. Neuropsychopharmacology 29:1918–1924

    CAS  PubMed  Google Scholar 

  • Brand A, Richter-Landsberg C, Leibfritz D (1993) Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci 15:289–298

    CAS  PubMed  Google Scholar 

  • Bremner JD (2006) Traumatic stress: effects on the brain. Dialogues Clin Neurosci 8:445–461

    PubMed  Google Scholar 

  • Brenner E, Kondziella D, Haberg A, Sonnewald U (2005) Impaired glutamine metabolism in NMDA receptor hypofunction induced by MK801. J Neurochem 94:1594–1603

    CAS  PubMed  Google Scholar 

  • Brooks GA (2002) Lactate shuttles in nature. Biochem Soc Trans 30:258–264

    CAS  PubMed  Google Scholar 

  • Brown AM (2004) Brain glycogen re-awakened. J Neurochem 89:537–552

    CAS  PubMed  Google Scholar 

  • Bustillo JR, Rowland LM, Jung R et al (2008) Proton magnetic resonance spectroscopy during initial treatment with antipsychotic medication in schizophrenia. Neuropsychopharmacology 33:2456–2466

    CAS  PubMed  Google Scholar 

  • Bustillo JR, Rowland LM, Mullins P et al (2010) 1H-MRS at 4 Tesla in minimally treated early schizophrenia. Mol Psychiatry 15:629–636

    CAS  PubMed  Google Scholar 

  • Capizzano AA, Jorge RE, Acion LC, Robinson RG (2007) In vivo proton magnetic resonance spectroscopy in patients with mood disorders: a technically oriented review. J Magn Reson Imaging 26:1378–1389

    PubMed  Google Scholar 

  • Caramanos Z, Narayanan S, Arnold DL (2005) 1H-MRS quantification of tNA and tCr in patients with multiple sclerosis: a meta-analytic review. Brain 128:2483–2506

    PubMed  Google Scholar 

  • Carder RK, Hendry SH (1994) Neuronal characterization, compartmental distribution, and activity-dependent regulation of glutamate immunoreactivity in adult monkey striate cortex. J Neurosci 14:242–262

    CAS  PubMed  Google Scholar 

  • Cecil KM, DelBello MP, Morey R, Strakowski SM (2002) Frontal lobe differences in bipolar disorder as determined by proton MR spectroscopy. Bipolar Disord 4:357–365

    CAS  PubMed  Google Scholar 

  • Chopra M, Yao Y, Blake TJ, Hampson DR, Johnson EC (2009) The neuroactive peptide N-acetylaspartylglutamate is not an agonist at the metabotropic glutamate receptor subtype 3 of metabotropic glutamate receptor. J Pharmacol Exp Ther 330:212–219

    CAS  PubMed  Google Scholar 

  • Choudary PV, Molnar M, Evans SJ et al (2005) Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc Natl Acad Sci U S A 102:15653–15658

    CAS  PubMed  Google Scholar 

  • Clark JB (1998) N-acetyl aspartate: a marker for neuronal loss or mitochondrial dysfunction. Dev Neurosci 20:271–276

    CAS  PubMed  Google Scholar 

  • Clark JF, Doepke A, Filosa JA, Wardle RL, Lu A, Meeker TJ, Pyne-Geithman GJ (2006) N-acetylaspartate as a reservoir for glutamate. Med Hypotheses 67:506–512

    CAS  PubMed  Google Scholar 

  • Colla M, Schubert F, Bubner M et al (2009) Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol. Mol Psychiatry 14:696–704, 647

    Google Scholar 

  • Coplan JD, Lydiard RB (1998) Brain circuits in panic disorder. Biol Psychiatry 44:1264–1276

    CAS  PubMed  Google Scholar 

  • Coryell MW, Ziemann AE, Westmoreland PJ et al (2007) Targeting ASIC1a reduces innate fear and alters neuronal activity in the fear circuit. Biol Psychiatry 62:1140–1148

    CAS  PubMed  Google Scholar 

  • Dager SR, Strauss WL, Marro KI, Richards TL, Metzger GD, Artru AA (1995) Proton magnetic resonance spectroscopy investigation of hyperventilation in subjects with panic disorder and comparison subjects. Am J Psychiatry 152:666–672

    Google Scholar 

  • Dager SR, Richards T, Strauss W, Artru A (1997) Single-voxel 1H-MRS investigation of brain metabolic changes during lactate-induced panic. Psychiatry Res 30:89–99

    Google Scholar 

  • Dager SR, Friedman SD, Heide A et al (1999) Two-dimensional proton echo-planar spectroscopic imaging of brain metabolic changes during lactate-induced panic. Arch Gen Psychiatry 56:70–77

    CAS  PubMed  Google Scholar 

  • Dager SR, Friedman SD, Parow A et al (2004) Brain metabolic alterations in medication-free patients with bipolar disorder. Arch Gen Psychiatry 61:450–458

    CAS  PubMed  Google Scholar 

  • De Stefano N, Matthews PM, Arnold DL (1995) Reversible decreases in N-acetylaspartate after acute brain injury. Magn Reson Med 34:721–727

    PubMed  Google Scholar 

  • Deicken RF, Johnson C, Pegues M (2000) Proton magnetic resonance spectroscopy of the human brain in schizophrenia. Rev Neurosci 11:147–158

    CAS  PubMed  Google Scholar 

  • Delp MD, Armstrong RB, Godfrey DA, Laughlin MH, Ross CD, Wilkerson MK (2001) Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine. J Physiol 533:849–859

    CAS  PubMed  Google Scholar 

  • Demougeot C, Marie C, Giroud M, Beley A (2004) N-acetylaspartate: a literature review of animal research on brain ischaemia. J Neurochem 90:776–783

    CAS  PubMed  Google Scholar 

  • Dericioglu N, Garganta CL, Petroff OA, Mendelsohn D, Williamson A (2008) Blockade of GABA synthesis only affects neural excitability under activated conditions in rat hippocampal slices. Neurochem Int 53:22–32

    CAS  PubMed  Google Scholar 

  • Dickstein DP, Towbin KE, Van Der Veen JW et al (2009) Randomized double-blind placebo-controlled trial of lithium in youths with severe mood dysregulation. J Child Adolesc Psychopharmacol 19:61–73

    PubMed  Google Scholar 

  • Dolder M, Walzel B, Speer O, Schlattner U, Wallimann T (2003) Inhibition of the mitochondrial permeability transition by creatine kinase substrates: requirement for microcompartmentation. J Biol Chem 278:17760–17766

    CAS  PubMed  Google Scholar 

  • Eastwood SL, Harrison PJ (2010) Markers of glutamate synaptic transmission and plasticity are increased in the anterior cingulate cortex in bipolar disorder. Biol Psychiatry 67:1010–1016

    CAS  PubMed  Google Scholar 

  • Edden RA, Pomper MG, Barker PB (2007) In vivo differentiation of N-acetyl aspartyl glutamate from N-acetyl aspartate at 3 Tesla. Magn Reson Med 57:977–982

    CAS  PubMed  Google Scholar 

  • Edden RA, Muthukumaraswamy SD, Freeman TC, Singh KD (2009) Orientation discrimination performance is predicted by GABA concentration and gamma oscillation frequency in human primary visual cortex. J Neurosci 29:15721–15726

    CAS  PubMed  Google Scholar 

  • Ellison-Wright I, Glahn DC, Laird AR, Thelen SM, Bullmore E (2008) The anatomy of first-episode and chronic schizophrenia: an anatomical likelihood estimation meta-analysis. Am J Psychiatry 165:1015–1023

    PubMed  Google Scholar 

  • Emsell L, McDonald C (2009) The structural neuroimaging of bipolar disorder. Int Rev Psychiatry 21:297–313

    PubMed  Google Scholar 

  • Epperson CN, Haga K, Mason GF et al (2002) 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 59:851–858

    CAS  PubMed  Google Scholar 

  • Erlichman JS, Hewitt A, Damon TL, Hart M, Kurascz J, Li A, Leiter JC (2008) Inhibition of monocarboxylate transporter 2 in the retrotrapezoid nucleus in rats: a test of the astrocyte-neuron lactate-shuttle hypothesis. J Neurosci 28:4888–4896

    CAS  PubMed  Google Scholar 

  • Esquivel G, Schruers KR, Maddock RJ, Colasanti A, Griez EJ (2010) Review: Acids in the brain: a factor in panic? J Psychopharmacol 24:639–647

    CAS  PubMed  Google Scholar 

  • Etkin A, Wager TD (2007) Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry 164:1476–1488

    PubMed  Google Scholar 

  • Fan Q, Tan L, You C et al (2010) Increased N-Acetylaspartate/creatine ratio in the medial prefrontal cortex among unmedicated obsessive-compulsive disorder patients. Psychiatry Clin Neurosci 64:483–490

    CAS  PubMed  Google Scholar 

  • Farrant M, Nusser Z (2005) Variations on an inhibitory theme: phasic and tonic activation of GABA(A) receptors. Nat Rev Neurosci 6:215–229

    CAS  PubMed  Google Scholar 

  • Ferrari MC, Busatto GF, McGuire PK, Crippa JA (2008) Structural magnetic resonance imaging in anxiety disorders: an update of research findings. Rev Bras Psiquiatr 30:251–264

    PubMed  Google Scholar 

  • Fisher SK, Novak JE, Agranoff BW (2002) Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance. J Neurochem 82:736–754

    CAS  PubMed  Google Scholar 

  • Friedman SD, Dager SR, Parow A et al (2004) Lithium and valproic acid treatment effects on brain chemistry in bipolar disorder. Biol Psychiatry 56:340–348

    CAS  PubMed  Google Scholar 

  • Friedman SD, Mathis CM, Hayes C, Renshaw P, Dager SR (2006) Brain pH response to hyperventilation in panic disorder: preliminary evidence for altered acid-base regulation. Am J Psychiatry 163:710–715

    PubMed  Google Scholar 

  • Frye MA, Watzl J, Banakar S et al (2007) Increased anterior cingulate/medial prefrontal cortical glutamate and creatine in bipolar depression. Neuropsychopharmacology 32:2490–2499

    CAS  PubMed  Google Scholar 

  • Fukuyama H, Ouchi Y, Matsuzaki S et al (1997) Brain functional activity during gait in normal subjects: a SPECT study. Neurosci Lett 228:183–186

    CAS  PubMed  Google Scholar 

  • Fukuzako H (2001) Neurochemical investigation of the schizophrenic brain by in vivo phosphorus magnetic resonance spectroscopy. World J Biol Psychiatry 2:70–82

    CAS  PubMed  Google Scholar 

  • Gaetz W, Edgar JC, Wang DJ, Roberts TP (2011) Relating MEG measured motor cortical oscillations to resting gamma-aminobutyric acid (GABA) concentration. Neuroimage 55:616–621. doi:10.1016/j.neuroimage.2010.12.077

    CAS  PubMed  Google Scholar 

  • Gasparovic C, Arfai N, Smid N, Feeney DM (2001) Decrease and recovery of N-acetylaspartate/creatine in rat brain remote from focal injury. J Neurotrauma 18:241–246

    CAS  PubMed  Google Scholar 

  • Geddes JW, Panchalingam K, Keller JN, Pettegrew JW (1997) Elevated phosphocholine and phosphatidylcholine following rat entorhinal cortex lesions. Neurobiol Aging 18:305–308

    CAS  PubMed  Google Scholar 

  • Gladden LB (2004) Lactate metabolism: a new paradigm for the third millennium. J Physiol 558:5–30

    CAS  PubMed  Google Scholar 

  • Goddard AW, Mason GF, Almai A et al (2001) Reductions in occipital cortex GABA levels in panic disorder detected with 1H-magnetic resonance spectroscopy. Arch Gen Psychiatry 58:556–561

    CAS  PubMed  Google Scholar 

  • Goddard AW, Mason GF, Appel M, Rothman DL, Gueorguieva R, Behar KL, Krystal JH (2004) Impaired GABA neuronal response to acute benzodiazepine administration in panic disorder. Am J Psychiatry 161:2186–2193

    PubMed  Google Scholar 

  • Gorman JM, Kent JM, Sullivan GM, Coplan JD (2000) Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry 157:493–505

    CAS  PubMed  Google Scholar 

  • Goto N, Yoshimura R, Moriya J et al (2009) Reduction of brain gamma-aminobutyric acid (GABA) concentrations in early-stage schizophrenia patients: 3T proton MRS study. Schizophr Res 112:192–193

    PubMed  Google Scholar 

  • Govindaraju V, Young K, Maudsley AA (2000) Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed 13:129–153

    CAS  PubMed  Google Scholar 

  • Griffin JL, Bollard M, Nicholson JK, Bhakoo K (2002) Spectral profiles of cultured neuronal and glial cells derived from HRMAS (1)H NMR spectroscopy. NMR Biomed 15:375–384

    CAS  PubMed  Google Scholar 

  • Gussew A, Rzanny R, Erdtel M, Scholle HC, Kaiser WA, Mentzel HJ, Reichenbach JR (2010) Time-resolved functional 1H MR spectroscopic detection of glutamate concentration changes in the brain during acute heat pain stimulation. Neuroimage 49:1895–1902

    CAS  PubMed  Google Scholar 

  • Hajek T, Kozeny J, Kopecek M, Alda M, Hoschl C (2008) Reduced subgenual cingulate volumes in mood disorders: a meta-analysis. J Psychiatry Neurosci 33:91–99

    PubMed  Google Scholar 

  • Hallcher LM, Sherman WR (1980) The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. J Biol Chem 255:10896–10901

    CAS  PubMed  Google Scholar 

  • Hamakawa H, Kato T, Murashita J, Kato N (1998) Quantitative proton magnetic resonance spectroscopy of the basal ganglia in patients with affective disorders. Eur Arch Psychiatry Clin Neurosci 248:53–58

    CAS  PubMed  Google Scholar 

  • Hancu I (2009) Optimized glutamate detection at 3T. J Magn Reson Imaging 30:1155–1162

    PubMed  Google Scholar 

  • Harada M, Kubo H, Nose A, Nishitani H, Matsuda T (2010) Measurement of variation in the human cerebral GABA level by in vivo MEGA-editing proton MR spectroscopy using a clinical 3 T instrument and its dependence on brain region and the female menstrual cycle. Hum Brain Mapp 32:828–833

    Google Scholar 

  • Hashimoto K, Engberg G, Shimizu E, Nordin C, Lindstrom LH, Iyo M (2005) Elevated glutamine/glutamate ratio in cerebrospinal fluid of first episode and drug naive schizophrenic patients. BMC Psychiatry 5:6

    PubMed  Google Scholar 

  • Hashimoto T, Hussien R, Cho HS, Kaufer D, Brooks GA (2008) Evidence for the mitochondrial lactate oxidation complex in rat neurons: demonstration of an essential component of brain lactate shuttles. PLoS ONE 3:e2915

    PubMed  Google Scholar 

  • Hasler G, Neumeister A, van der Veen JW et al (2005) Normal prefrontal gamma-aminobutyric acid levels in remitted depressed subjects determined by proton magnetic resonance spectroscopy. Biol Psychiatry 58:969–973

    CAS  PubMed  Google Scholar 

  • Hasler G, van der Veen JW, Tumonis T, Meyers N, Shen J, Drevets WC (2007) Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry 64:193–200

    CAS  PubMed  Google Scholar 

  • Hasler G, Nugent AC, Carlson PJ, Carson RE, Geraci M, Drevets WC (2008) Altered cerebral gamma-aminobutyric acid type A-benzodiazepine receptor binding in panic disorder determined by [11C]flumazenil positron emission tomography. Arch Gen Psychiatry 65:1166–1175

    PubMed  Google Scholar 

  • Hasler G, van der Veen JW, Geraci M, Shen J, Pine D, Drevets WC (2009) Prefrontal cortical gamma-aminobutyric acid levels in panic disorder determined by proton magnetic resonance spectroscopy. Biol Psychiatry 65:273–275

    CAS  PubMed  Google Scholar 

  • Hercher C, Turecki G, Mechawar N (2009) Through the looking glass: examining neuroanatomical evidence for cellular alterations in major depression. J Psychiatr Res 43:947–961

    PubMed  Google Scholar 

  • Hertz L (2004) Intercellular metabolic compartmentation in the brain: past, present and future. Neurochem Int 45:285–296

    CAS  PubMed  Google Scholar 

  • Hertz L (2006) Glutamate, a neurotransmitter—and so much more: a synopsis of Wierzba III. Neurochem Int 48:416–425

    CAS  PubMed  Google Scholar 

  • Hettema JM, Neale MC, Kendler KS (2001) A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry 158:1568–1578

    CAS  PubMed  Google Scholar 

  • Horn DI, Yu C, Steiner J et al (2010) Glutamatergic and resting-state functional connectivity correlates of severity in major depression—the role of pregenual anterior cingulate cortex and anterior insula. Front Syst Neurosci 4:33

    Google Scholar 

  • Hu Y, Wilson GS (1997) A temporary local energy pool coupled to neuronal activity: fluctuations of extracellular lactate levels in rat brain monitored with rapid-response enzyme-based sensor. J Neurochem 69:1484–1490

    CAS  PubMed  Google Scholar 

  • Huey ED, Zahn R, Krueger F, Moll J, Kapogiannis D, Wassermann EM, Grafman J (2008) A psychological and neuroanatomical model of obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci 20:390–408

    PubMed  Google Scholar 

  • Iltis I, Koski DM, Eberly LE et al (2009) Neurochemical changes in the rat prefrontal cortex following acute phencyclidine treatment: an in vivo localized (1)H MRS study. NMR Biomed 22:737–744

    CAS  PubMed  Google Scholar 

  • Iosifescu DV, Bolo NR, Nierenberg AA, Jensen JE, Fava M, Renshaw PF (2008) Brain bioenergetics and response to triiodothyronine augmentation in major depressive disorder. Biol Psychiatry 63:1127–1134

    CAS  PubMed  Google Scholar 

  • Jaaro-Peled H, Ayhan Y, Pletnikov MV, Sawa A (2010) Review of pathological hallmarks of schizophrenia: comparison of genetic models with patients and nongenetic models. Schizophr Bull 36:301–313

    PubMed  Google Scholar 

  • Janaky R, Cruz-Aguado R, Oja SS, Shaw CA (2007) Glutathione in the nervous system: roles in neural function and health and implications for neurological disease. In: Lajtha A, Oja S, Schousboe A, Saransaari P (eds) Handbook of neurochemistry and molecular neurobiology: amino acids and peptides in the nervous system. Springer, New York

    Google Scholar 

  • Jang JH, Kwon JS, Jang DP et al (2006) A proton MRSI study of brain N-acetylaspartate level after 12 weeks of citalopram treatment in drug-naive patients with obsessive-compulsive disorder. Am J Psychiatry 163:1202–1207

    PubMed  Google Scholar 

  • Jensen JE, Miller J, Williamson PC et al (2006) Grey and white matter differences in brain energy metabolism in first episode schizophrenia: 31P-MRS chemical shift imaging at 4 Tesla. Psychiatry Res 146:127–135

    CAS  PubMed  Google Scholar 

  • Jensen JE, Licata SC, Ongur D, Friedman SD, Prescot AP, Henry ME, Renshaw PF (2009) Quantification of J-resolved proton spectra in two-dimensions with LCModel using GAMMA-simulated basis sets at 4 Tesla. NMR Biomed 22:762–769

    CAS  PubMed  Google Scholar 

  • Kalra S, Cashman NR, Genge A, Arnold DL (1998) Recovery of N-acetylaspartate in corticomotor neurons of patients with ALS after riluzole therapy. Neuroreport 9:1757–1761

    CAS  PubMed  Google Scholar 

  • Karl A, Schaefer M, Malta LS, Dorfel D, Rohleder N, Werner A (2006) A meta-analysis of structural brain abnormalities in PTSD. Neurosci Biobehav Rev 30:1004–1031

    PubMed  Google Scholar 

  • Karolewicz B, Maciag D, O’Dwyer G, Stockmeier CA, Feyissa AM, Rajkowska G (2010) Reduced level of glutamic acid decarboxylase-67 kDa in the prefrontal cortex in major depression. Int J Neuropsychopharmacol 13:411–420

    CAS  PubMed  Google Scholar 

  • Kato T, Hamakawa H, Shioiri T, Murashita J, Takahashi Y, Takahashi S, Inubushi T (1996) Choline-containing compounds detected by proton magnetic resonance spectroscopy in the basal ganglia in bipolar disorder. J Psychiatry Neurosci 21:248–254

    CAS  PubMed  Google Scholar 

  • Kauppinen RA, Williams SR (1991) Nondestructive detection of glutamate by 1H nuclear magnetic resonance spectroscopy in cortical brain slices from the guinea pig: evidence for changes in detectability during severe anoxic insults. J Neurochem 57:1136–1144

    CAS  PubMed  Google Scholar 

  • Kim H, McGrath BM, Silverstone PH (2005) A review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI-cycle) to psychiatric disorders—focus on magnetic resonance spectroscopy (MRS) studies. Hum Psychopharmacol 20:309–326

    CAS  PubMed  Google Scholar 

  • Klein DF (1993) False suffocation alarms, spontaneous panics, and related conditions: an integrative hypothesis. Arch Gen Psychiatry 50:306–317

    Google Scholar 

  • Klempan TA, Sequeira A, Canetti L, Lalovic A, Ernst C, Ffrench-Mullen J, Turecki G (2009) Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression. Mol Psychiatry 14:175–189

    CAS  PubMed  Google Scholar 

  • Knox D, Perrine SA, George SA, Galloway MP, Liberzon I (2010) Single prolonged stress decreases glutamate, glutamine, and creatine concentrations in the rat medial prefrontal cortex. Neurosci Lett 480:16–20

    CAS  PubMed  Google Scholar 

  • Koenigs M, Huey ED, Raymont V, Cheon B, Solomon J, Wassermann EM, Grafman J (2008) Focal brain damage protects against post-traumatic stress disorder in combat veterans. Nat Neurosci 11:232–237

    CAS  PubMed  Google Scholar 

  • Koga Y, Takahashi H, Oikawa D, Tachibana T, Denbow DM, Furuse M (2005) Brain creatine functions to attenuate acute stress responses through GABAnergic system in chicks. Neuroscience 132:65–71

    CAS  PubMed  Google Scholar 

  • Konarski JZ, McIntyre RS, Kennedy SH, Rafi-Tari S, Soczynska JK, Ketter TA (2008) Volumetric neuroimaging investigations in mood disorders: bipolar disorder versus major depressive disorder. Bipolar Disord 10:1–37

    PubMed  Google Scholar 

  • Kondo DG, Hellem TL, Sung YH et al (2011) Review: magnetic resonance spectroscopy studies of pediatric major depressive disorder. Depress Res Treat 2011:650450

    PubMed  Google Scholar 

  • Kosenko E, Llansola M, Montoliu C et al (2003) Glutamine synthetase activity and glutamine content in brain: modulation by NMDA receptors and nitric oxide. Neurochem Int 43:493–499

    CAS  PubMed  Google Scholar 

  • Krishnan V, Nestler EJ (2008) The molecular neurobiology of depression. Nature 455:894–902

    CAS  PubMed  Google Scholar 

  • Lan MJ, McLoughlin GA, Griffin JL et al (2009) Metabonomic analysis identifies molecular changes associated with the pathophysiology and drug treatment of bipolar disorder. Mol Psychiatry 14:269–279

    CAS  PubMed  Google Scholar 

  • Layton ME, Friedman SD, Dager SR (2001) Brain metabolic changes during lactate-induced panic: effects of gabapentin treatment. Dep Anxiety 14:251–254

    CAS  Google Scholar 

  • Lei H, Berthet C, Hirt L, Gruetter R (2009) Evolution of the neurochemical profile after transient focal cerebral ischemia in the mouse brain. J Cereb Blood Flow Metab 29:811–819

    CAS  PubMed  Google Scholar 

  • Liberzon I, Sripada CS (2008) The functional neuroanatomy of PTSD: a critical review. Prog Brain Res 167:151–169

    PubMed  Google Scholar 

  • Lisman JE, Coyle JT, Green RW, Javitt DC, Benes FM, Heckers S, Grace AA (2008) Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci 31:234–242

    CAS  PubMed  Google Scholar 

  • Maciag D, Hughes J, O’Dwyer G, Pride Y, Stockmeier CA, Sanacora G, Rajkowska G (2010) Reduced density of calbindin immunoreactive GABAergic neurons in the occipital cortex in major depression: relevance to neuroimaging studies. Biol Psychiatry 67:465–470

    CAS  PubMed  Google Scholar 

  • Maciejewski PK, Rothman DL (2008) Proposed cycles for functional glutamate trafficking in synaptic neurotransmission. Neurochem Int 52:809–825

    CAS  PubMed  Google Scholar 

  • MacMaster FP, Moore GJ, Russell A, Mirza Y, Taormina SP, Buhagiar C, Rosenberg DR (2008) Medial temporal N-acetyl-aspartate in pediatric major depression. Psychiatry Res 164:86–89

    CAS  PubMed  Google Scholar 

  • Maddock RJ (2001) The lactic acid response to alkalosis in panic disorder: an integrative review. J Neuropsychiatry Clin Neurosci 13:22–34

    CAS  PubMed  Google Scholar 

  • Maddock RJ, Buonocore MH (2008) Measuring brain lactate at rest and during visual stimulation. Psychiatry Res 162:175–179

    CAS  Google Scholar 

  • Maddock RJ, Buonocore MH (2010) Abnormal metabolic activation of fear and arousal responses as a model of vulnerability to panic disorder. In: Anxiety disorders association of America annual meeting, Baltimore, MA

    Google Scholar 

  • Maddock RJ, Buonocore MH, Lavoie SP, Copeland LE, Kile SJ, Richards AL, Ryan JM (2006) Brain lactate responses during visual stimulation in fasting and hyperglycemic subjects: a proton magnetic resonance spectroscopy study at 1.5 Tesla. Psychiatry Research: Neuroimaging 148:47–54

    CAS  PubMed  Google Scholar 

  • Maddock RJ, Buonocore MH, Copeland LE, Richards AL (2009) Elevated brain lactate responses to neural activation in panic disorder: a dynamic 1H-MRS study. Mol Psychiatry 14:537–545

    CAS  PubMed  Google Scholar 

  • Maddock RJ, Casazza GA, Buonocore MH, Tanase C (2011) Vigorous exercise increases brain lactate and Glx (glutamate + glutamine): a dynamic 1H-MRS study. Neuroimage. doi:10.1016/j.neuroimage.2011.05.048

    PubMed  Google Scholar 

  • Mangia S, Tkac I, Gruetter R, Van de Moortele PF, Maraviglia B, Ugurbil K (2007) Sustained neuronal activation raises oxidative metabolism to a new steady-state level: evidence from 1H NMR spectroscopy in the human visual cortex. J Cereb Blood Flow Metab 27:1055–1063

    CAS  PubMed  Google Scholar 

  • Manji HK, Moore GJ, Chen G (2000) Clinical and preclinical evidence for the neurotrophic effects of mood stabilizers: implications for the pathophysiology and treatment of manic-depressive illness. Biol Psychiatry 48:740–754

    CAS  PubMed  Google Scholar 

  • Mann EO, Mody I (2010) Control of hippocampal gamma oscillation frequency by tonic inhibition and excitation of interneurons. Nat Neurosci 13:205–212

    CAS  PubMed  Google Scholar 

  • Mescher M, Merkle H, Kirsch J, Garwood M, Gruetter R (1998) Simultaneous in vivo spectral editing and water suppression. NMR Biomed 11:266–272

    CAS  PubMed  Google Scholar 

  • Meyer LE, Machado LB, Santiago AP et al (2006) Mitochondrial creatine kinase activity prevents reactive oxygen species generation: antioxidant role of mitochondrial kinase-dependent ADP re-cycling activity. J Biol Chem 281:37361–37371

    CAS  PubMed  Google Scholar 

  • Meyerhoff DJ, MacKay S, Bachman L, Poole N, Dillon WP, Weiner MW, Fein G (1993) Reduced brain N-acetylaspartate suggests neuronal loss in cognitively impaired human immunodeficiency virus-seropositive individuals: in vivo 1H magnetic resonance spectroscopic imaging. Neurology 43:509–515

    CAS  PubMed  Google Scholar 

  • Meyer-Lindenberg A (2010) From maps to mechanisms through neuroimaging of schizophrenia. Nature 468:194–202

    CAS  PubMed  Google Scholar 

  • Michael N, Erfurth A, Ohrmann P, Arolt V, Heindel W, Pfleiderer B (2003a) Neurotrophic effects of electroconvulsive therapy: a proton magnetic resonance study of the left amygdalar region in patients with treatment-resistant depression. Neuropsychopharmacology 28:720–725

    CAS  PubMed  Google Scholar 

  • Michael N, Erfurth A, Ohrmann P, Gossling M, Arolt V, Heindel W, Pfleiderer B (2003b) Acute mania is accompanied by elevated glutamate/glutamine levels within the left dorsolateral prefrontal cortex. Psychopharmacology (Berl) 168:344–346

    CAS  Google Scholar 

  • Michael N, Erfurth A, Pfleiderer B (2009) Elevated metabolites within dorsolateral prefrontal cortex in rapid cycling bipolar disorder. Psychiatry Res 172:78–81

    CAS  PubMed  Google Scholar 

  • Miguel-Hidalgo JJ, Waltzer R, Whittom AA, Austin MC, Rajkowska G, Stockmeier CA (2010) Glial and glutamatergic markers in depression, alcoholism, and their comorbidity. J Affect Disord 127:230–240

    CAS  PubMed  Google Scholar 

  • Moffett JR, Ross B, Arun P, Madhavarao CN, Namboodiri AM (2007) N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol 81:89–131

    CAS  PubMed  Google Scholar 

  • Mohamed MA, Smith MA, Schlund MW, Nestadt G, Barker PB, Hoehn-Saric R (2007) Proton magnetic resonance spectroscopy in obsessive-compulsive disorder: a pilot investigation comparing treatment responders and non-responders. Psychiatry Res 156:175–179

    PubMed  Google Scholar 

  • Moore CM, Christensen JD, Lafer B, Fava M, Renshaw PF (1997) Lower levels of nucleoside triphosphate in the basal ganglia of depressed subjects: a phosphorous-31 magnetic resonance spectroscopy study. Am J Psychiatry 154:116–118

    CAS  PubMed  Google Scholar 

  • Moore GJ, Bebchuk JM, Hasanat K et al (2000) Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2’s neurotrophic effects? Biol Psychiatry 48:1–8

    CAS  PubMed  Google Scholar 

  • Mullins PG, Rowland LM, Jung RE, Sibbitt WL Jr (2005) A novel technique to study the brain’s response to pain: proton magnetic resonance spectroscopy. Neuroimage 26:642–646

    PubMed  Google Scholar 

  • Muthukumaraswamy SD, Edden RA, Jones DK, Swettenham JB, Singh KD (2009) Resting GABA concentration predicts peak gamma frequency and fMRI amplitude in response to visual stimulation in humans. Proc Natl Acad Sci U S A 106:8356–8361

    CAS  PubMed  Google Scholar 

  • Narayanan S, De Stefano N, Francis GS et al (2001) Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b. J Neurol 248:979–986

    CAS  PubMed  Google Scholar 

  • Neale JH, Bzdega T, Wroblewska B (2000) N-Acetylaspartylglutamate: the most abundant peptide neurotransmitter in the mammalian central nervous system. J Neurochem 75:443–452

    CAS  PubMed  Google Scholar 

  • O’Donnell T, Rotzinger S, Ulrich M, Hanstock CC, Nakashima TT, Silverstone PH (2003) Effects of chronic lithium and sodium valproate on concentrations of brain amino acids. Eur Neuropsychopharmacol 13:220–227

    PubMed  Google Scholar 

  • Ongur D, Jensen JE, Prescot AP, Stork C, Lundy M, Cohen BM, Renshaw PF (2008) Abnormal glutamatergic neurotransmission and neuronal-glial interactions in acute mania. Biol Psychiatry 64:718–726

    CAS  PubMed  Google Scholar 

  • Ongur D, Prescot AP, McCarthy J, Cohen BM, Renshaw PF (2010) Elevated gamma-aminobutyric acid levels in chronic schizophrenia. Biol Psychiatry 68:667–670

    PubMed  Google Scholar 

  • Pae CU, Choe BY, Joo RH et al (2004) Neuronal dysfunction of the frontal lobe in schizophrenia. Neuropsychobiology 50:211–215

    PubMed  Google Scholar 

  • Pajonk FG, Wobrock T, Gruber O et al (2010) Hippocampal plasticity in response to exercise in schizophrenia. Arch Gen Psychiatry 67:133–143

    PubMed  Google Scholar 

  • Patel NC, DelBello MP, Cecil KM, Adler CM, Bryan HS, Stanford KE, Strakowski SM (2006) Lithium treatment effects on myo-inositol in adolescents with bipolar depression. Biol Psychiatry 60:998–1004

    CAS  PubMed  Google Scholar 

  • Patel NC, DelBello MP, Cecil KM, Stanford KE, Adler CM, Strakowski SM (2008) Temporal change in N-acetyl-aspartate concentrations in adolescents with bipolar depression treated with lithium. J Child Adolesc Psychopharmacol 18:132–139

    PubMed  Google Scholar 

  • Pauls DL (2010) The genetics of obsessive-compulsive disorder: a review. Dialogues Clin Neurosci 12:149–163

    PubMed  Google Scholar 

  • Pellerin L, Bouzier-Sore AK, Aubert A, Serres S, Merle M, Costalat R, Magistretti PJ (2007) Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55:1251–1262

    PubMed  Google Scholar 

  • Petroff OA, Prichard JW, Behar KL, Alger JR, den Hollander JA, Shulman RG (1985) Cerebral intracellular pH by 31P nuclear magnetic resonance spectroscopy. Neurology 35:781–788

    CAS  PubMed  Google Scholar 

  • Petroff OA, Hyder F, Rothman DL, Mattson RH (2001) Topiramate rapidly raises brain GABA in epilepsy patients. Epilepsia 42:543–548

    CAS  PubMed  Google Scholar 

  • Pierre K, Pellerin L (2005) Monocarboxylate transporters in the central nervous system: distribution, regulation and function. J Neurochem 94:1–14

    CAS  PubMed  Google Scholar 

  • Port JD, Unal SS, Mrazek DA, Marcus SM (2008) Metabolic alterations in medication-free patients with bipolar disorder: a 3T CSF-corrected magnetic resonance spectroscopic imaging study. Psychiatry Res 162:113–121

    CAS  PubMed  Google Scholar 

  • Pouwels PJ, Frahm J (1997) Differential distribution of NAA and NAAG in human brain as determined by quantitative localized proton MRS. NMR Biomed 10:73–78

    CAS  PubMed  Google Scholar 

  • Premkumar P, Parbhakar VA, Fannon D, Lythgoe D, Williams SC, Kuipers E, Kumari V (2010) N-acetyl aspartate concentration in the anterior cingulate cortex in patients with schizophrenia: a study of clinical and neuropsychological correlates and preliminary exploration of cognitive behaviour therapy effects. Psychiatry Res 182:251–260

    CAS  PubMed  Google Scholar 

  • Price RB, Shungu DC, Mao X et al (2009) Amino acid neurotransmitters assessed by proton magnetic resonance spectroscopy: relationship to treatment resistance in major depressive disorder. Biol Psychiatry 65:792–800

    CAS  PubMed  Google Scholar 

  • Prichard J, Rothman D, Novotny E et al (1991) Lactate rise detected by 1H NMR in human visual cortex during physiologic stimulation. Proc Natl Acad Sci U S A 88:5829–5831

    CAS  PubMed  Google Scholar 

  • Protopopescu X, Pan H, Tuescher O et al (2006) Increased brainstem volume in panic disorder: a voxel-based morphometric study. Neuroreport 17:361–363

    PubMed  Google Scholar 

  • Qu Y, Massie A, Van der Gucht E et al (2003) Retinal lesions affect extracellular glutamate levels in sensory-deprived and remote non-deprived regions of cat area 17 as revealed by in vivo microdialysis. Brain Res 962:199–206

    CAS  PubMed  Google Scholar 

  • Quiroz JA, Machado-Vieira R, Zarate CA Jr, Manji HK (2010) Novel insights into lithium’s mechanism of action: neurotrophic and neuroprotective effects. Neuropsychobiology 62:50–60

    CAS  PubMed  Google Scholar 

  • Radua J, Mataix-Cols D (2009) Voxel-wise meta-analysis of grey matter changes in obsessive-compulsive disorder. Br J Psychiatry 195:393–402

    PubMed  Google Scholar 

  • Radua J, van den Heuvel OA, Surguladze S, Mataix-Cols D (2010) Meta-analytical comparison of voxel-based morphometry studies in obsessive-compulsive disorder vs other anxiety disorders. Arch Gen Psychiatry 67:701–711

    PubMed  Google Scholar 

  • Rajkowska G, O’Dwyer G, Teleki Z, Stockmeier CA, Miguel-Hidalgo JJ (2007) GABAergic neurons immunoreactive for calcium binding proteins are reduced in the prefrontal cortex in major depression. Neuropsychopharmacology 32:471–482

    CAS  PubMed  Google Scholar 

  • Reynolds LM, Reynolds GP (2011) Differential regional N-acetylaspartate deficits in postmortem brain in schizophrenia, bipolar disorder and major depressive disorder. J Psychiatr Res 45:54–59

    PubMed  Google Scholar 

  • Rodrigo R, Felipo V (2007) Control of brain glutamine synthesis by NMDA receptors. Front Biosci 12:883–890

    CAS  PubMed  Google Scholar 

  • Roelants-Van Rijn AM, van der Grond J, de Vries LS, Groenendaal F (2001) Value of (1)H-MRS using different echo times in neonates with cerebral hypoxia-ischemia. Pediatr Res 49:356–362

    CAS  PubMed  Google Scholar 

  • Rotge JY, Guehl D, Dilharreguy B et al (2009) Meta-analysis of brain volume changes in obsessive-compulsive disorder. Biol Psychiatry 65:75–83

    PubMed  Google Scholar 

  • Rothman DL, Behar KL, Hyder F, Shulman RG (2003) In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: implications for brain function. Annu Rev Physiol 65:401–427

    CAS  PubMed  Google Scholar 

  • Rowland LM, Bustillo JR, Mullins PG et al (2005) Effects of ketamine on anterior cingulate glutamate metabolism in healthy humans: a 4-T proton MRS study. Am J Psychiatry 162:394–396

    PubMed  Google Scholar 

  • Royes LF, Fighera MR, Furian AF et al (2008) Neuromodulatory effect of creatine on extracellular action potentials in rat hippocampus: role of NMDA receptors. Neurochem Int 53:33–37

    CAS  PubMed  Google Scholar 

  • Salo R, Buonocore MH, Leamon M et al (2011) Extended findings of brain metabolite normalization in MA-dependent subjects across sustained abstinence: a proton MRS study. Drug Alcohol Depend 113:133–138

    Google Scholar 

  • Sanacora G, Mason GF, Rothman DL et al (1999) Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch Gen Psychiatry 56:1043–1047

    CAS  PubMed  Google Scholar 

  • Sanacora G, Mason GF, Rothman DL, Krystal JH (2002) Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. Am J Psychiatry 159:663–665

    PubMed  Google Scholar 

  • Sanacora G, Mason GF, Rothman DL et al (2003) Increased cortical GABA concentrations in depressed patients receiving ECT. Am J Psychiatry 160:577–579

    PubMed  Google Scholar 

  • Sanacora G, Gueorguieva R, Epperson CN et al (2004) Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry 61:705–713

    CAS  PubMed  Google Scholar 

  • Sanacora G, Fenton LR, Fasula MK, Rothman DL, Levin Y, Krystal JH, Mason GF (2006) Cortical gamma-aminobutyric acid concentrations in depressed patients receiving cognitive behavioral therapy. Biol Psychiatry 59:284–286

    CAS  PubMed  Google Scholar 

  • Sappey-Marinier D, Calabrese G, Fein G, Hugg JW, Biggins C, Weiner MW (1992) Effect of photic stimulation on human visual cortex lactate and phosphates using 1H and 31P magnetic resonance spectroscopy. J Cereb Blood Flow Metab 12:584–592

    CAS  PubMed  Google Scholar 

  • Savitz J, Drevets WC (2009) Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide. Neurosci Biobehav Rev 33:699–771

    PubMed  Google Scholar 

  • Schmidt H, Schwaller B, Eilers J (2005) Calbindin D28k targets myo-inositol monophosphatase in spines and dendrites of cerebellar Purkinje neurons. Proc Natl Acad Sci U S A 102:5850–5855

    CAS  PubMed  Google Scholar 

  • Schuff N, Neylan TC, Fox-Bosetti S et al (2008) Abnormal N-acetylaspartate in hippocampus and anterior cingulate in posttraumatic stress disorder. Psychiatry Res 162:147–157

    CAS  PubMed  Google Scholar 

  • Selemon LD, Goldman-Rakic PS (1999) The reduced neuropil hypothesis: a circuit based model of schizophrenia. Biol Psychiatry 45:17–25

    CAS  PubMed  Google Scholar 

  • Senaratne R, Milne AM, MacQueen GM, Hall GB (2009) Increased choline-containing compounds in the orbitofrontal cortex and hippocampus in euthymic patients with bipolar disorder: a proton magnetic resonance spectroscopy study. Psychiatry Res 172:205–209

    PubMed  Google Scholar 

  • Sequeira A, Mamdani F, Ernst C et al (2009) Global brain gene expression analysis links glutamatergic and GABAergic alterations to suicide and major depression. PLoS One 4:e6585

    PubMed  Google Scholar 

  • Shibuya-Tayoshi S, Tayoshi S, Sumitani S, Ueno S, Harada M, Ohmori T (2008) Lithium effects on brain glutamatergic and GABAergic systems of healthy volunteers as measured by proton magnetic resonance spectroscopy. Prog Neuropsychopharmacol Biol Psychiatry 32:249–256

    CAS  PubMed  Google Scholar 

  • Shirayama Y, Obata T, Matsuzawa D et al (2010) Specific metabolites in the medial prefrontal cortex are associated with the neurocognitive deficits in schizophrenia: a preliminary study. Neuroimage 49:2783–2790

    CAS  PubMed  Google Scholar 

  • Siegmund A, Kaltwasser SF, Holsboer F, Czisch M, Wotjak CT (2009) Hippocampal N-acetylaspartate levels before trauma predict the development of long-lasting posttraumatic stress disorder-like symptoms in mice. Biol Psychiatry 65:258–262

    CAS  PubMed  Google Scholar 

  • Signoretti S, Di Pietro V, Vagnozzi R et al (2010) Transient alterations of creatine, creatine phosphate, N-acetylaspartate and high-energy phosphates after mild traumatic brain injury in the rat. Mol Cell Biochem 333:269–277

    CAS  PubMed  Google Scholar 

  • Silverstone PH, McGrath BM (2009) Lithium and valproate and their possible effects on themyo-inositol second messenger system in healthy volunteers and bipolar patients. Int Rev Psychiatry 21:414–423

    PubMed  Google Scholar 

  • Smesny S, Rosburg T, Nenadic I et al (2007) Metabolic mapping using 2D 31P-MR spectroscopy reveals frontal and thalamic metabolic abnormalities in schizophrenia. Neuroimage 35:729–737

    PubMed  Google Scholar 

  • Smith EA, Russell A, Lorch E et al (2003) Increased medial thalamic choline found in pediatric patients with obsessive-compulsive disorder versus major depression or healthy control subjects: a magnetic resonance spectroscopy study. Biol Psychiatry 54:1399–1405

    CAS  PubMed  Google Scholar 

  • Star-Lack J, Spielman D, Adalsteinsson E, Kurhanewicz J, Terris DJ, Vigneron DB (1998) In vivo lactate editing with simultaneous detection of choline, creatine, NAA, and lipid singlets at 1.5 T using PRESS excitation with applications to the study of brain and head and neck tumors. J Magn Reson 133:243–254

    CAS  PubMed  Google Scholar 

  • Steen RG, Hamer RM, Lieberman JA (2005) Measurement of brain metabolites by 1H magnetic resonance spectroscopy in patients with schizophrenia: a systematic review and meta-analysis. Neuropsychopharmacology 30:1949–1962

    CAS  PubMed  Google Scholar 

  • Stone JM (2009) Imaging the glutamate system in humans: relevance to drug discovery for schizophrenia. Curr Pharm Des 15:2594–2602

    CAS  PubMed  Google Scholar 

  • Stork C, Renshaw PF (2005) Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research. Mol Psychiatry 10:900–919

    CAS  PubMed  Google Scholar 

  • Taylor MJ, Selvaraj S, Norbury R, Jezzard P, Cowen PJ (2009) Normal glutamate but elevated myo-inositol in anterior cingulate cortex in recovered depressed patients. J Affect Disord 119:186–189

    CAS  PubMed  Google Scholar 

  • Tayoshi S, Nakataki M, Sumitani S et al (2011) GABA concentration in schizophrenia patients and the effects of antipsychotic medication: a proton magnetic resonance spectroscopy study. Schizophr Res 117:83–91

    Google Scholar 

  • Theberge J, Bartha R, Drost DJ et al (2002) Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Am J Psychiatry 159:1944–1946

    PubMed  Google Scholar 

  • Theberge J, Al-Semaan Y, Williamson PC et al (2003) Glutamate and glutamine in the anterior cingulate and thalamus of medicated patients with chronic schizophrenia and healthy comparison subjects measured with 4.0-T proton MRS. Am J Psychiatry 160:2231–2233

    PubMed  Google Scholar 

  • Trzesniak C, Araujo D, Crippa JAS (2008) Magnetic resonance spectroscopy in anxiety disorders. Acta Neuropsychiatr 20:56–71

    Google Scholar 

  • Uchida RR, Del-Ben CM, Busatto GF et al (2008) Regional gray matter abnormalities in panic disorder: a voxel-based morphometry study. Psychiatry Res 163:21–29

    PubMed  Google Scholar 

  • Uhlhaas PJ, Singer W (2010) Abnormal neural oscillations and synchrony in schizophrenia. Nat Rev Neurosci 11:100–113

    CAS  PubMed  Google Scholar 

  • Urenjak J, Williams SR, Gadian DG, Noble M (1993) Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci 13:981–989

    CAS  PubMed  Google Scholar 

  • Valentine GW, Sanacora G (2009) Targeting glial physiology and glutamate cycling in the treatment of depression. Biochem Pharmacol 78:431–439

    CAS  PubMed  Google Scholar 

  • van Tol MJ, van der Wee NJ, van den Heuvel OA et al (2010) Regional brain volume in depression and anxiety disorders. Arch Gen Psychiatry 67:1002–1011

    PubMed  Google Scholar 

  • Volz HP, Rzanny R, Riehemann S et al (1998) 31P magnetic resonance spectroscopy in the frontal lobe of major depressed patients. Eur Arch Psychiatry Clin Neurosci 248:289–295

    CAS  PubMed  Google Scholar 

  • Waagepetersen HS, Sonnewald U, Schousboe A (2007) Glutamine, Glutamate, and GABA: metabolic aspects. In: Lajtha A, Oja S, Schousboe A, Saransaari P (eds) Handbook of neurochemistry and molecular neurobiology: amino acids and peptides in the nervous system. Springer, New York, pp 1–21

    Google Scholar 

  • Walter M, Henning A, Grimm S et al (2009) The relationship between aberrant neuronal activation in the pregenual anterior cingulate, altered glutamatergic metabolism, and anhedonia in major depression. Arch Gen Psychiatry 66:478–486

    CAS  PubMed  Google Scholar 

  • Weber OM, Verhagen A, Duc CO, Meier D, Leenders KL, Boesiger P (1999) Effects of vigabatrin intake on brain GABA activity as monitored by spectrally edited magnetic resonance spectroscopy and positron emission tomography. Magn Reson Imaging 17:417–425

    CAS  PubMed  Google Scholar 

  • Williams RS, Cheng L, Mudge AW, Harwood AJ (2002) A common mechanism of action for three mood-stabilizing drugs. Nature 417:292–295

    CAS  PubMed  Google Scholar 

  • Winsberg ME, Sachs N, Tate DL, Adalsteinsson E, Spielman D, Ketter TA (2000) Decreased dorsolateral prefrontal N-acetyl aspartate in bipolar disorder. Biol Psychiatry 47:475–481

    CAS  PubMed  Google Scholar 

  • Wright IC, Rabe-Hesketh S, Woodruff PW, David AS, Murray RM, Bullmore ET (2000) Meta-analysis of regional brain volumes in schizophrenia. Am J Psychiatry 157:16–25

    CAS  PubMed  Google Scholar 

  • Wu Y, Wang W, Diez-Sampedro A, Richerson GB (2007) Nonvesicular inhibitory neurotransmission via reversal of the GABA transporter GAT-1. Neuron 56:851–865

    CAS  PubMed  Google Scholar 

  • Yacubian J, de Castro CC, Ometto M et al (2002) 31P-spectroscopy of frontal lobe in schizophrenia: alterations in phospholipid and high-energy phosphate metabolism. Schizophr Res 58:117–122

    PubMed  Google Scholar 

  • Yang D, Xie Z, Stephenson D et al (2011) Volumetric MRI and MRS provide sensitive measures of Alzheimer’s disease neuropathology in inducible Tau transgenic mice (rTg4510). Neuroimage 54:2652−2658

    Google Scholar 

  • Yildiz A, Sachs GS, Dorer DJ, Renshaw PF (2001) 31P Nuclear magnetic resonance spectroscopy findings in bipolar illness: a meta-analysis. Psychiatry Res 106:181–191

    CAS  PubMed  Google Scholar 

  • Yildiz-Yesiloglu A, Ankerst DP (2006a) Neurochemical alterations of the brain in bipolar disorder and their implications for pathophysiology: a systematic review of the in vivo proton magnetic resonance spectroscopy findings. Prog Neuropsychopharmacol Biol Psychiatry 30:969–995

    CAS  PubMed  Google Scholar 

  • Yildiz-Yesiloglu A, Ankerst DP (2006b) Review of 1H magnetic resonance spectroscopy findings in major depressive disorder: a meta-analysis. Psychiatry Res 147:1–25

    CAS  PubMed  Google Scholar 

  • Yoon JH, Rokem AS, Silver MA, Minzenberg MJ, Ursu S, Ragland JD, Carter CS (2009) Diminished orientation-specific surround suppression of visual processing in schizophrenia. Schizophr Bull 35:1078–1084

    PubMed  Google Scholar 

  • Yoon JH, Maddock RJ, Rokem A, Silver MA, Minzenberg MJ, Ragland JD, Carter CS (2010a) GABA concentration is reduced in visual cortex in schizophrenia and correlates with orientation-specific surround suppression. J Neurosci 30:3777–3781

    CAS  PubMed  Google Scholar 

  • Yoon SJ, Lyoo IK, Kim HJ et al (2010b) Neurochemical alterations in methamphetamine-dependent patients treated with cytidine-5′-diphosphate choline: a longitudinal proton magnetic resonance spectroscopy study. Neuropsychopharmacology 35:1165–1173

    CAS  PubMed  Google Scholar 

  • Yucel M, Harrison BJ, Wood SJ et al (2007) Functional and biochemical alterations of the medial frontal cortex in obsessive-compulsive disorder. Arch Gen Psychiatry 64:946–955

    CAS  PubMed  Google Scholar 

  • Yue Q, Shibata Y, Isobe T, Anno I, Kawamura H, Gong QY, Matsumura A (2009) Absolute choline concentration measured by quantitative proton MR spectroscopy correlates with cell density in meningioma. Neuroradiology 51:61–67

    PubMed  Google Scholar 

  • Yuksel C, Ongur D (2010) Magnetic resonance spectroscopy studies of glutamate-related abnormalities in mood disorders. Biol Psychiatry 68:785–794

    PubMed  Google Scholar 

  • Zarate CA Jr, Singh JB, Carlson PJ et al (2006) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63:856–864

    CAS  PubMed  Google Scholar 

  • Ziemann AE, Allen JE, Dahdaleh NS et al (2009) The amygdala is a chemosensor that detects carbon dioxide and acidosis to elicit fear behavior. Cell 139:1012–1021

    CAS  PubMed  Google Scholar 

  • Zink M, Vollmayr B, Gebicke-Haerter PJ, Henn FA (2010) Reduced expression of glutamate transporters vGluT1, EAAT2 and EAAT4 in learned helpless rats, an animal model of depression. Neuropharmacology 58:465–473

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. University of California Davis Medical Center, Sacramento, CA, USA

    Richard J. Maddock & Michael H. Buonocore

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  1. Richard J. Maddock
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  2. Michael H. Buonocore
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Correspondence to Richard J. Maddock .

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Editors and Affiliations

  1. , UC Davis Imaging Center, University of California at Davis, X Street 4701, Sacramento, 95817, California, USA

    Cameron S. Carter

  2. , Dep of Experimental Psychology/Dep of Ps, University of Cambridge, Downing Site, Cambridge, CB2 3EB, United Kingdom

    Jeffrey W. Dalley

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Maddock, R.J., Buonocore, M.H. (2011). MR Spectroscopic Studies of the Brain in Psychiatric Disorders. In: Carter, C., Dalley, J. (eds) Brain Imaging in Behavioral Neuroscience. Current Topics in Behavioral Neurosciences, vol 11. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2011_197

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