Brain GABA levels across psychiatric disorders: A systematic literature review and meta-analysis of 1H-MRS studies

Human Brain Mapping

Volumn 37, Issue 9, 2016, Pages 3337-3352

  Schür, Remmelt R ^a   Draisma, Luc W R ^a   Wijnen, Jannie P ^a   Boks, Marco P ^a   Koevoets, Martijn G J C ^a   Joëls, Marian ^a   Klomp, Dennis W ^a   Kahn, René S ^a   Vinkers, Christiaan H ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

1H MRS; ASD; GABA; MDD; meta analysis; psychopathology

Indexed keywords

4 AMINOBUTYRIC ACID;

AGE; ATTENTION DEFICIT DISORDER; AUTISM; BIPOLAR DISORDER; BRAIN LEVEL; HUMAN; MAJOR DEPRESSION; MENTAL DISEASE; PANIC; POSTTRAUMATIC STRESS DISORDER; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; REVIEW; SCHIZOPHRENIA; SYSTEMATIC REVIEW;

EID: 84982972138     PISSN: 10659471     EISSN: 10970193     Source Type: Journal    
DOI: 10.1002/hbm.23244     Document Type: Review

References (117)

1. Abdallah C, Jiang L, De Feyter H, Fasula M, Krystal JH, Rothman DL, Mason GF, Sanacora G (2014): Glutamate metabolism in major depressive disorder. Am J Psychiatry 171:1320–1327.
2. Andreychenko A, Boer VO, Arteaga De Castro CS, Luijten PR, Klomp DWJ (2012): Efficient spectral editing at 7 T: GABA detection with MEGA-sLASER. Magn Reson Med 68:1018–1025.
3. Aoki Y, Kasai K, Yamasue H (2012): Age-related change in brain metabolite abnormalities in autism: A meta-analysis of proton magnetic resonance spectroscopy studies. Transl Psychiatry 2:e69.
4. Arteaga De Castro C, Boer V, Andreychenko A, Wijnen J, Van der Heide U, Luijten P, Klomp D (2013): Improved efficiency on editing MRS of lactate and gamma-aminobutyric acid by inclusion of frequency offset corrected inversion pulses at high fields. NMR Biomed 26:1213–1219.
5. Aufhaus E, Weber-Fahr W, Sack M, Tunc-Skarka N, Oberthuer G, Hoerst M, Meyer-Lindenberg A, Boettcher U, Ende G (2013): Absence of changes in GABA concentrations with age and gender in the human anterior cingulate cortex: A MEGA-PRESS study with symmetric editing pulse frequencies for macromolecule suppression. Magn Reson Med 69:317–320.
6. Barnes SA, Kappe A, Zembrzycki A, Metzler A, Mukamel EA, Lucero J, Wang X, Sejnowski TJ (2015): Disruption of mGluR5 in parvalbumin-positive interneurons induces core features of neurodevelopmental disorders. Mol Psychiatry 20:1161–1172.
7. Behar KL, Rothman DL, Petersen KF, Hooten M, Delaney R, Petroff OAC, Shulman GI, Navarro V, Petrakis IL, Charney DS, Krystal JH (1999): Preliminary evidence of low cortical GABA levels in localized 1H-MR spectra of alcohol-dependent and hepatic encephalopathy patients. Am J Psychiatry 156:952–954.
8. Berrettini WH, Nurnberger JI, Hare T, Gershon ES, Post RM (1982): Plasma and CSF GABA in affective illness. Br J Psychiatry 141:483–487.
9. Bhagwagar Z, Wylezinska M, Jezzard P, Evans J, Ashworth F, Sule A, Matthews PM, Cowen PJ (2007): Reduction in occipital cortex gamma-aminobutyric acid concentrations in medication-free recovered unipolar depressed and bipolar subjects. Biol Psychiatry 61:806–812.
10. Bhagwagar Z, Wylezinska M, Jezzard P, Evans J, Boorman E, M Matthews P, J Cowen P (2008): Low GABA concentrations in occipital cortex and anterior cingulate cortex in medication-free, recovered depressed patients. Int J Neuropsychopharmacol 11:255–260.
11. Boer VO, Van de Lindt T, Luijten PR, Klomp DWJ (2015): Lipid suppression for brain MRI and MRSI by means of a dedicated crusher coil. Magn Reson Med 73:2062–2068.
12. Bogner W, Gruber S, Doelken M, Stadlbauer A, Ganslandt O, Boettcher U, Trattnig S, Doerfler A, Stefan H, Hammen T (2010): In vivo quantification of intracerebral GABA by single-voxel 1H-MRS-How reproducible are the results? Eur J Radiol 73:526–531.
13. Bollmann S, Ghisleni C, Poil S, Martin E, Ball J, Eich-Höchli D, Edden R, Klaver P, Michels L, Brandeis D, O'Gorman RL (2015): Developmental changes in gamma-aminobutyric acid levels in attention-deficit/hyperactivity disorder. Transl Psychiatry 5:e589.
14. Borenstein M, Hedges L, Higgins J, Rothstein H (2005): Comprehensive Meta-Analysis Version 2. Engelwood, NJ: Biostat.
15. Brady RO, Mccarthy JM, Prescot AP, Jensen JE, Cooper AJ, Cohen BM, Renshaw PF, Öngür D (2013): Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder. Bipolar Disord 15:434–439.
16. Brambilla P, Perez J, Barale F, Schettini G, Soares JC (2003): GABAergic dysfunction in mood disorders. Mol Psychiatry 8:721–715.
17. Brix MK, Ersland L, Hugdahl K, Grüner R, Posserud M, Hammar Å, Craven AR, Noeske R (2015): “Brain MR spectroscopy in autism spectrum disorder — the GABA excitatory/inhibitory imbalance theory revisited.”. Front Hum Neurosci 9:1–12.
18. Brondino N, Fusar-Poli L, Panisi C, Damiani S, Barale F, Politi P (2015): Pharmacological modulation of gaba function in autism spectrum disorders: A systematic review of human studies. J Autism Dev Disord 46:825–839.
19. Bruining H, Passtoors L, Goriounova N, Jansen F, Hakvoort B, De Jonge M, Poil S (2015): Paradoxical benzodiazepine response: A rationale for bumetanide in neurodevelopmental disorders? Pediatrics 136:e539–e543.
20. Cai K, Nanga RP, Lamprou L, Schinstine C, Elliott M, Hariharan H, Reddy R, Epperson CN (2012): The impact of gabapentin administration on brain gaba and glutamate concentrations: A 7t 1h-mrs study. Neuropsychopharmacology 37:2764–2771.
21. Chen CMA, Stanford AD, Mao X, Abi-Dargham A, Shungu DC, Lisanby SH, Schroeder CE, Kegeles LS (2014): GABA level, gamma oscillation, and working memory performance in schizophrenia. NeuroImage Clin 4:531–539.
22. Cochran DM, Sikoglu EM, Hodge SM, Edden RAE, Foley A, Kennedy DN, Moore CM, Frazier JA (2015): Relationship among glutamine, gamma-aminobutyric acid, and social cognition in autism spectrum disorders. J Child Adolesc Psychopharmacol 25:314–322.
23. Dhossche D, Applegate H, Abraham A, Maertens P, Bland L, Bencsath A, Martinez J (2002): Elevated plasma gamma-aminobutyric acid (GABA) levels in autistic youngsters: Stimulus for a GABA hypothesis of autism. Med Sci Monit 8:PR1–PR6.
24. Edden R, Crocetti D, Zhu H, Gilbert D, Mostofsky S (2012): Reduced GABA concentration in attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 69:750–753.
25. Egger M, Davey Smith G, Schneider M, Minder C (1997): Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634.
26. El-Ansary AK, Bacha AB, Al-Ayahdi LY (2011): Relationship between chronic lead toxicity and plasma neurotransmitters in autistic patients from Saudi Arabia. Clin Biochem 44:1116–1120.
27. Ende G, Cackowski S, Van Eijk J, Sack M, Demirakca T, Kleindienst N, Bohus M, Sobanski E, Krause-Utz A, Schmahl C (2015): Impulsivity and aggression in female bpd and adhd patients: Association with acc glutamate and gaba concentrations. Neuropsychopharmacology 41:410–418.
28. Epperson CN, Haga K, Mason GF, Sellers E, Gueorguieva R, Zhang W, Weiss E, Rothman D, Krystal JH (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.
29. Epperson CN, Malley SO, Czarkowski KA, Gueorguieva R, 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. Biol Psychiatry 57:44–48.
30. Epperson CN, Gueorguieva R, Czarkowski KA, Stiklus S, Sellers E, Krystal JH, Rothman DL, Mason GF (2006): Preliminary evidence of reduced occipital GABA concentrations in puerperal women: A 1H-MRS study. Psychopharmacology (Berl) 186:425–433.
31. Evans CJ, McGonigle DJ, Edden RAE (2010): Diurnal stability of γ-aminobutyric acid concentration in visual and sensorimotor cortex. J Magn Reson Imaging 31:204–209.
32. Fatemi SH, Halt AR, Stary JM, Kanodia R, Schulz SC, Realmuto GR (2002): Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices. Biol Psychiatry 52:805–810.
33. Fatemi SH, Reutiman TJ, Folsom TD, Rustan OG, Rooney RJ, Thuras PD (2014): Downregulation of GABAA receptor protein subunits alpha6, beta2, delta, eta, gamma2, theta, and rho2 in superior frontal cortex of subjects with autism. J Autism Dev Disord 44:1833–1845.
34. Frankle WG, Cho RY, Prasad KM, Mason NS, Paris J, Himes M, Walker C, Lewis D, Narendran R (2015): In vivo measurement of gaba transmission in healthy subjects and schizophrenia patients. Am J Psychiatry 172:1148–1159.
35. Gabbay V, Mao X, Klein R, Ely B, Babb J, Panzer A, Alonso C, Shungu D (2012): Anterior cingulate cortex gamma-aminobutyric acid in depressed adolescents: Relationship to anhedonia. Arch Gen Psychiatry 69:139–149.
36. Gaetz W, Bloy L, Wang D, Port R, Blaskey L, Levy S, ROberts T (2014): GABA estimation in the brains of children on the autism spectrum: Measurement precision and regional cortical variation. Neuroimage 86:1–9.
37. Gerner R, Fairbanks L, Anderson G, Young J, Scheinin M, Linnoila M, Hare T, Shaywitz B, Cohen D (1984): CSF neurochemistry in depressed, manic, and schizophrenic patients compared with that of normal controls. Am J Psychiatry 141:1533–1540.
38. Geuze E, van Berckel BNM, Lammertsma AA, Boellaard R, de Kloet CS, Vermetten E, Westenberg HGM (2008): Reduced GABAA benzodiazepine receptor binding in veterans with post-traumatic stress disorder. Mol Psychiatry 13:74–83.
39. Goddard AW, Mason GF, Almai A, Rothman DL, Behar KL, Petroff OAC, Charney DS, Krystal JH (2001): Reductions in occipital cortex GABA levels in panic disorder detected with 1h-magnetic resonance spectroscopy. Arch Gen Psychiatry 58:556–561.
40. Gonzalez-Burgos G, Cho RY, Lewis DA (2015): Alterations in cortical network oscillations and parvalbumin neurons in schizophrenia. Biol Psychiatry 77:1031–1040.
41. Goto N, Yoshimura R, Moriya J, Kakeda S, Ueda N, Ikenouchi-Sugita A, Umene-Nakano W, Hayashi K, Oonari N, Korogi Y, Nakamura J (2009): Reduction of brain gamma-aminobutyric acid (GABA) concentrations in early-stage schizophrenia patients: 3T Proton MRS study. Schizophr Res 112:192–193.
42. Govindaraju V, Young K, Maudsley A (2000): Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed 13:129–153.
43. Harada M, Taki MM, Nose A, Kubo H, Mori K, Nishitani H, Matsuda T (2011): Non-invasive evaluation of the GABAergic/glutamatergic system in autistic patients observed by MEGA-editing proton MR spectroscopy using a clinical 3 tesla instrument. J Autism Dev Disord 41:447–454.
44. Hasler G, Neumeister A, Van Der Veen JW, Tumonis T, Bain EE, Shen J, Drevets WC, Charney DS (2005): Normal prefrontal gamma-aminobutyric acid levels in remitted depressed subjects determined by proton magnetic resonance spectroscopy. Biol Psychiatry 58:969–973.
45. 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.
46. Hasler G, Veen JW, Van Der 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.
47. Hasler G, van der Veen JW, Grillon C, Drevets WC, Shen J (2010): Effect of acute psychological stress on prefrontal GABA concentration determined by proton magnetic resonance spectroscopy. Am J Psychiatry 167:1226–1231.
48. Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003): Measuring inconsistency in meta-analyses. BMJ Br Med J 327:557–560.
49. Hussman JP (2001): Suppressed gabaergic inhibition as a common factor in suspected etiologies of autism. J Autism Dev Disord 31:247–248.
50. Jackson MF, Esplin B, Čapek R (2000): Reversal of the activity-dependent suppression of GABA-mediated inhibition in hippocampal slices from γ-vinyl GABA (vigabatrin)-pretreated rats. Neuropharmacology 39:65–74.
51. Kalueff AV, Nutt DJ (2007): Role of GABA in anxiety and depression. Depress Anxiety 24:495–517.
52. Kasa K, Otsuki S, Yamamoto M, Sato M, Kuroda H, Ogawa N (1982): Cerebrospinal fluid gamma-aminobutyric acid and homovanillic acid in depressive disorders. Biol Psychiatry 17:877–883.
53. Kaufman RE, Ostacher MJ, Marks EH, Simon NM, Sachs GS, Jensen JE, Renshaw PF, Pollack MH (2009): Brain GABA levels in patients with bipolar disorder. Prog Neuro-Psychopharmacol Biol Psychiatry 33:427–434.
54. Ke Y, Streeter CC, Nassar LE, Sarid-Segal O, Hennen J, Yurgelun-Todd DA, Awad LA, Rendall MJ, Gruber SA, Nason A, Mudrick MJ, Blank SR, Meyer AA, Knapp C, Ciraulo DA, Renshaw PF (2004): Frontal lobe GABA levels in cocaine dependence: A two- dimensional, J-resolved magnetic resonance spectroscopy study. Psychiatry Res 130:283–293.
55. Kegeles LS, Mao X, Stanford AD, Girgis R, Ojeil N, Xu X, Gil R, Slifstein M, Abi-Dargham A, Lisanby SH, Shungu DC (2012): Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy. Arch Gen Psychiatry 69:449–459.
56. Kelemen O, Kiss I, Benedek G, Kéri S (2013): Perceptual and cognitive effects of antipsychotics in first-episode schizophrenia: The potential impact of GABA concentration in the visual cortex. Prog Neuro-Psychopharmacol Biol Psychiatry 47:13–19.
57. Koenigs M, Grafman J (2009): Posttraumatic stress disorder: The role of medial prefrontal cortex and amygdala. Neuroscientist 15:540–548.
58. Kugaya A, Sanacora G, Verhoeff NPLG, Fujita M, Mason GF, Seneca NM, Bozkurt A, Khan SA, Anand A, Degen K, Charney DS, Zoghbi SS, Baldwin RM, Seibyl JP, Innis RB (2003): Cerebral benzodiazepine receptors in depressed patients measured with [123I]iomazenil SPECT. Biol Psychiatry 54:792–799.
59. Kumar S, Porcu P, Werner D, Matthews D, Diaz-Granados J, Helfand R, Morrow A (2009): The role of GABAA receptors in the acute and chronic effects of ethanol: A decade of progress. Psychopharmacology 205:529–564.
60. Lewis DA, Hashimoto T, Volk DW (2005): Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 6:312–324.
61. Liu B, Wang G, Gao D, Gao F, Zhao B, Qiao M, Yang H, Yu Y, Ren F, Yang P, Chen W, Rae CD (2015): Alterations of GABA and glutamate-glutamine levels in premenstrual dysphoric disorder: A 3T proton magnetic resonance spectroscopy study. Psychiatry Res Neuroimaging 231:64–70.
62. Long Z, Medlock C, Dzemidzic M, Shin YW, Goddard AW, Dydak U (2013): Decreased GABA levels in anterior cingulate cortex/medial prefrontal cortex in panic disorder. Prog Neuropsychopharmacol Biol Psychiatry 44:131–135.
63. Luscher B, Shen Q, Sahir N (2011): The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry 16:383–406.
64. Luykx JJ, Laban KG, Van Den HMP, Boks MPM, Mandl RCW (2012a): Region and state specific glutamate downregulation in major depressive disorder: A meta-analysis of 1 H-MRS findings. Neurosci Biobehav Rev 36:198–205.
65. Luykx JJ, Vinkers CH, Bakker SC, Visser WF, van Boxmeer L, Strengman E, van Eijk KR, Lens JA, Borgdorff P, Keijzers P, Kappen TH, van Dongen EPA, Bruins P, Verhoeven NM, de Koning TJ, Kahn RS, Ophoff RA (2012b): A common variant in ERBB4 regulates GABA concentrations in human cerebrospinal fluid. Neuropsychopharmacology 37:2088–2092.
66. Marín O (2012): Interneuron dysfunction in psychiatric disorders. Nat Rev Neurosci 13:107–120.
67. Marsman A, Mandl RCW, Klomp DWJ, Bohlken MM, Boer VO, Andreychenko A, Cahn W, Kahn RS, Luijten PR, Hulshoff Pol HE (2014): GABA and glutamate in schizophrenia: A 7 T 1H-MRS study. NeuroImage Clin 6:398–407.
68. Mason GF, Petrakis IL, Graaf RA, De Gueorguieva R, Guidone E, Coric V, Epperson CN, Rothman DL Krystal JH (2006): Cortical gamma-aminobutyric acid levels and the recovery from ethanol dependence: preliminary evidence of modification by cigarette smoking. Biol Psychiatry 59:85–93.
69. Mendez MA, Horder J, Myers J, Coghlan S, Stokes P, Erritzoe D, Howes O, Lingford-Hughes A, Murphy D, Nutt D (2013): The brain GABA-benzodiazepine receptor alpha-5 subtype in autism spectrum disorder: A pilot [11C]Ro15-4513 positron emission tomography study. Neuropharmacology 68:195–201.
70. Michels L, Schulte-Vels T, Schick M, O'Gorman RL, Zef T, Hasler G, Mueller-Pfeiffer C (2014): Prefrontal GABA and glutathione imbalance in posttraumatic stress disorder: Preliminary findings. Psychiatry Res Neuroimaging 224:288–295.
71. Mody I, Pearce RA (2004): Diversity of inhibitory neurotransmission through GABA A receptors. Trends Neurosci 27:569–575.
72. Moher D, Liberati A, Tetzlaff J, Altman D, PRISMA G. r (2009): Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. BMJ 339:b2535.
73. Möhler H (2007): Molecular regulation of cognitive functions and developmental plasticity: Impact of GABAA receptors. J Neurochem 102:1–12.
74. Mori T, Mori K, Fujii E, Toda Y, Miyazaki M, Harada M, Hashimoto T, Kagami S (2012): Evaluation of the GABAergic nervous system in autistic brain: 123I-iomazenil SPECT study. Brain Dev 34:648–654.
75. Mullins PG, McGonigle DJ, O'Gorman RL, Puts NAJ, Vidyasagar R, Evans CJ, Edden RAE, Brookes MJ, Garcia A, Foerster BR, Petrou M, Price D, Solanky BS, Violante IR, Williams S, Wilson M (2014): Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA. Neuroimage 86:43–52.
76. Nakazawa K, Zsiros V, Jiang Z, Nakao K, Kolata S, Zhang S, Belforte JE (2012): GABAergic interneuron origin of schizophrenia pathophysiology. Neuropharmacology 62:1574–1583.
77. Near J, Evans C, Puts N, Barker P, Edden R (2013): J-difference editing of gamma-aminobutyric acid (GABA): Simulated and experimental multiplet patterns. Magn Reson Med 70:1183–1191.
78. Near J, Ho YL, Sandberg K, Kumaragamage C, Blicher JU (2014): Long-term reproducibility of GABA magnetic resonance spectroscopy. Neuroimage 99:191–196.
79. O'Gorman RL, Michels L, Edden RA, James B, Martin E (2011): NIH Public Access. J Magn Reson Imaging 33:1262–1267.
80. Öngür D, Prescot AP, McCarthy J, Cohen BM, Renshaw PF (2010): Elevated gamma-aminobutyric acid levels in chronic schizophrenia. Biol Psychiatry 68:667–670.
81. Pennington DL, Abé C, Batki SL, Meyerhoff DJ (2014): A preliminary examination of cortical neurotransmitter levels associated with heavy drinking in posttraumatic stress disorder. Psychiatry Res Neuroimaging 224:281–287.
82. Petroff OAC (2002): GABA and glutamate in the human brain. Neuroscientist 8:562–573.
83. Petty F, Sherman AD (1984): Plasma GABA levels in psychiatric illness. J Affect Disord 6:131–138.
84. Petty F, Kramer GL, Gullion CM, Rush AJ (1992): Low plasma gamma-aminobutyric acid levels in male patients with depression. Biol Psychiatry 32:354–363.
85. Petty F, Kramer GL, Fulton M, Davis L, Rush AJ (1995): Stability of plasma GABA at four-year follow-up in patients with primary unipolar depression. Biol Psychiatry 37:806–810.
86. Plante DT, Jensen JE, Schoerning L, Winkelman JW (2012): Reduced gamma-aminobutyric acid in occipital and anterior cingulate cortices in primary insomnia: A link to major depressive disorder? Neuropsychopharmacology 37:1548–1557.
87. Pollack MH, Jensen JE, Simon NM, Kaufman RE, Renshaw PF (2008): High-field MRS study of GABA, glutamate and glutamine in social anxiety disorder: Response to treatment with levetiracetam. Prog Neuropsychopharmacol Biol Psychiatry 32:739–743.
88. Price RB, Shungu DC, Mao X, Nestadt P, Kelly C, Collins KA, Murrough JW, Charney DS, Mathew SJ (2009): Amino acid neurotransmitters assessed by proton magnetic resonance spectroscopy: Relationship to treatment resistance in major depressive disorder. Biol Psychiatry 65:792–800.
89. Puts N, Edden R (2012): In vivo magnetic spectroscopy of GABA: A methodological review. Prog Nucl Magn Spectrosc 60:1–26.
90. 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.
91. Rivero O, Selten MM, Sich S, Popp S, Bacmeister L, Amendola E, Negwer M, Schubert D, Proft F, Kiser D, Schmitt AG, Gross C, Kolk S, Strekalova T, Van den Hove D, Resink T, Nadif Kasri N, Lesch K (2015): Cadherin-13, a risk gene for ADHD and comorbid disorders, impacts GABAergic function in hippocampus and cognition. Transl Psychiatry 5:e655.
92. Rojas DC, Singel D, Steinmetz S, Hepburn S, Brown MS (2014): Decreased left perisylvian GABA concentration in children with autism and unaffected siblings. Neuroimage 86:28–34.
93. Rolf LH, Haarmann FY, Grotemeyer KH, Kehrer H (1993): Serotonin and amino acid content in platelets of autistic children. Acta Psychiatr Scand 87:312–316.
94. Rosso IM, Weiner MR, Crowley DJ, Silveri MM, Rauch SL, Jensen JE (2014): Insula and anterior cingulate GABA levels in post-traumatic stress disorder: Preliminary findings using magnetic resonance spectroscopy. Depress Anxiety 31:115–123.
95. Rothman DL, Petroff OA, Behar KL, Mattson RH (1993): Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo. Proc Natl Acad Sci U S A 90:5662–5666.
96. Rowland LM, Kontson K, West J, Edden RA, Zhu H, Wijtenburg SA, Holcomb HH, Barker PB (2013): In vivo measurements of glutamate, GABA, and NAAG in schizophrenia. Schizophr Bull 39:1096–1104.
97. Rowland LM, Krause BW, Wijtenburg SA, Mcmahon RP, Chiappelli J, Nugent KL, Nisonger SJ, Korenic SA, Kochunov P (2015): Medial frontal GABA is lower in older schizophrenia: A MEGA-PRESS with macromolecule suppression study. Mol Psychiatry 21:198–204.
98. Russo AJ (2013): Correlation between hepatocyte growth factor (hgf) and gamma-aminobutyric acid (gaba) plasma levels in autistic children. Biomark Insights 8:69–75.
99. Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, Petroff OA, Berman RM, Charney DS, Krystal JH (1999): Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch Gen Psychiatry 56:1043–1047.
100. 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.
101. Sanacora G, Mason GF, Rothman DL, Hyder F, Ciarcia JJ, Ostroff RB, Berman RM, Krystal JH (2003): Increased cortical GABA concentrations in depressed patients receiving ECT. Am J Psychiatry 160:577–579.
102. Sanacora G, Gueorguieva R, Epperson CN, Wu Y-T, Appel M, Rothman DL, Krystal JH, Mason GF (2004): Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry 61:705–713.
103. 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.
104. Shaw A, Brealy J, Richardson H, Muthukumaraswamy SD, Edden RA, John Evans C, Puts NAJ, Singh KD, Keedwell PA (2013): Marked reductions in visual evoked responses but not gamma-aminobutyric acid concentrations or gamma-band measures in remitted depression. Biol Psychiatry 73:691–698.
105. Simpson HB, Shungu DC, Bender JJ, Mao X, Xu X, Slifstein M, Kegeles LS (2012): Investigation of cortical glutamate-glutamine and gamma-aminobutyric acid in obsessive-compulsive disorder by proton magnetic resonance spectroscopy. Neuropsychopharmacology 37:2684–2692.
106. Stan A, Ghose S, Zhao C, Hulsey K, Mihalakos P, Yanagi M, Morris S, Bartko J, Choi C, Tamminga C (2015): Magnetic resonance spectroscopy and tissue protein concentrations together suggest lower glutamate signaling in dentate gyrus in schizophrenia. Mol Psychiatry 20:433–439.
107. Stephenson MC, Gunner F, Napolitano A, Greenhaff PL, Macdonald IA, Saeed N, Vennart W, Francis ST, Morris PG, Stephenson MC, Francis ST, Morris PG (2011): Applications of multi-nuclear magnetic resonance spectroscopy at 7T. World J Radiol 3:105–113.
108. Tayoshi S, Nakataki M, Sumitani S, Taniguchi K, Shibuya-Tayoshi S, Numata S, Iga JI, Ueno SI, Harada M, Ohmori T (2010): GABA concentration in schizophrenia patients and the effects of antipsychotic medication: A proton magnetic resonance spectroscopy study. Schizophr Res 117:83–91.
109. Tinaz S, Belluscio BA, Malone P, Van der Veen JW, Hallett M, Horovitz SG (2014): Role of the sensorimotor cortex in Tourette syndrome using multimodal imaging. Hum Brain Mapp 35:5834–5846.
110. Vinkers CH, Mirza NR, Olivier B, Kahn RS (2010): The inhibitory GABA system as a therapeutic target for cognitive symptoms in schizophrenia: Investigational agents in the pipeline. Expert Opin Investig Drugs 19:1217–1233.
111. Walter M, Henning A, Grimm S, Schulte RF, Beck J, Dydak U, Schnepf B, Boeker H, Boesiger P, Northoff G (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.
112. Wang P, Sailasuta N, Chandler R, Ketter T (2006): Magnetic resonance spectroscopic measure- ment of cerebral gamma-aminobutyric acid concentrations in patients with bipolar disorders. Acta Neuropsychiatr 18:120–126.
113. Wijtenburg AS, Rowland LM, Edden RA, Barker PB, Phil D (2013): Reproducibility of brain spectroscopy at 7T using conventional localization and spectral editing techniques. J Magn Reson Imaging 38:460–467.
114. Wijtenburg SA, Yang S, Fischer BA, Rowland LM (2015): In vivo assessment of neurotransmitters and modulators with magnetic resonance spectroscopy: Application to schizophrenia. Neurosci Biobehav Rev 51:276–295.
115. Winkelman JW, Buxton OM, Jensen JE, Benson KL, Connor SPO, Wang W, Renshaw PF (2008): Reduced brain GABA in primary insomnia: Preliminary data from 4T proton magnetic resonance spectroscopy (1H-MRS). Sleep 31:1499–1506.
116. Yip J, Soghomonian JJ, Blatt GJ (2009): Decreased GAD65 mRNA levels in select subpopulations of neurons in the cerebellar dentate nuclei in autism: An in situ hybridization study. Autism Res 2:50–59.
117. Yoon JH, Maddock RJ, Rokem A, Silver MA, Minzenberg MJ, Ragland JD, Carter CS (2010): GABA concentration is reduced in visual cortex in schizophrenia and correlates with orientation-specific surround suppression. J Neurosci 30:3777–3781.