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Chapter 9 - Imaging Glutamatergic and GABAergic Abnormalities in Mood Disorders

from Section 3 - Functional and Neurochemical Brain Studies

Published online by Cambridge University Press:  12 January 2021

By
Estêvão Scotti-Muzzi ,
Maria Concepcion Garcia Otaduy ,
Márcio Gerhardt Soeiro-de-Souza  and
Rodrigo Machado-Vieira
Edited by
Sudhakar Selvaraj ,
Paolo Brambilla  and
Jair C. Soares
Sudhakar Selvaraj
Affiliation:
UTHealth School of Medicine, USA
Paolo Brambilla
Affiliation:
Università degli Studi di Milano
Jair C. Soares
Affiliation:
UT Harris County Psychiatric Center, USA
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Summary

Glutamate (Glu) and gamma-aminobutyric acid (GABA) are the main brain excitatory and inhibitory neurotransmitters. These neurotransmitters are involved in neural migration, differentiation, and synaptic plasticity (1–6). There are accumulating evidence in literature that the neurobiology of mood disorders may arise from an imbalance between excitatory Glu (7–11) and inhibitory GABA (12–15) in key brain regions involved in mood regulation, such as the anterior cingulate cortex (ACC).

Type
Chapter
Information
Mood Disorders
Brain Imaging and Therapeutic Implications
 , pp. 105 - 120
Publisher: Cambridge University Press
Print publication year: 2021

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References

Francis, PT, Poynton, A, Lowe, SL, et al. Brain amino acid concentrations and Ca2+-dependent release in intractable depression assessed antemortem. Brain Res. 1989; 494(2): 315–324.CrossRefGoogle ScholarPubMed
Stagg, CJ, Bestmann, S, Constantinescu, AO, et al. Relationship between physiological measures of excitability and levels of glutamate and GABA in the human motor cortex. J Physiol (Lond). 2011; 589(Pt 23): 5845–5855.Google Scholar
Eastwood, SL, Harrison, PJ. Markers of glutamate synaptic transmission and plasticity are increased in the anterior cingulate cortex in bipolar disorder. Biol Psychiatry. 2010; 67(11): 1010–1016.Google Scholar
Rossignol, E. Genetics and function of neocortical GABAergic interneurons in neurodevelopmental disorders. Neural Plast. 2011; 2011: 649325.Google Scholar
Fatemi, SH, Hossein Fatemi, S, Stary, JM, et al. GABAergic dysfunction in schizophrenia and mood disorders as reflected by decreased levels of glutamic acid decarboxylase 65 and 67 kDa and Reelin proteins in cerebellum. Schizophr Res. 2005; 72(2–3): 109–122.Google Scholar
Torrey, EF, Barci, BM, Webster, MJ, et al. Neurochemical markers for schizophrenia, bipolar disorder, and major depression in postmortem brains. Biol Psychiatry. 2005; 57(3): 252–260.Google Scholar
Ongür, D, Drevets, WC, Price, JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA. 1998; 95(22): 13290–13295.CrossRefGoogle ScholarPubMed
Yüksel, C, Ongur, D. Magnetic resonance spectroscopy studies of glutamate-related abnormalities in mood disorders. Biol Psychiatry. 2010; 68(9): 785–794.Google Scholar
Cotter, DR, Pariante, CM, Everall, IP. Glial cell abnormalities in major psychiatric disorders: the evidence and implications. Brain Res Bull. 2001; 55(5): 585–595.Google Scholar
Machado-Vieira, R, Salvadore, G, Ibrahim, LA, Diaz-Granados, N, Zarate, CA. Targeting glutamatergic signaling for the development of novel therapeutics for mood disorders. Curr Pharm Des. 2009; 15(14): 1595–1611.Google Scholar
Machado-Vieira, R, Manji, HK, Zarate, CA. The role of the tripartite glutamatergic synapse in the pathophysiology and therapeutics of mood disorders. Neuroscientist. 2009; 15(5): 525–539.Google Scholar
Kim, JS, Schmid-Burgk, W, Claus, D, Kornhuber, HH. Increased serum glutamate in depressed patients. Arch Psychiatr Nervenkr. 1982; 232(4): 299–304.Google Scholar
Brady, RO, McCarthy, JM, Prescot, AP, et al. Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder. Bipolar Disord. 2013; 15(4): 434–439.Google Scholar
Altamura, CA, Mauri, MC, Ferrara, A, et al. Plasma and platelet excitatory amino acids in psychiatric disorders. Am J Psychiatry. 1993; 150(11): 1731–1733.Google Scholar
Mauri, MC, Ferrara, A, Boscati, L, et al. Plasma and platelet amino acid concentrations in patients affected by major depression and under fluvoxamine treatment. Neuropsychobiology. 1998; 37(3): 124–129.Google Scholar
Rajkowska, G. Cell pathology in mood disorders. Semin Clin Neuropsychiatry. 2002; 7(4): 281–292.Google Scholar
Levine, J, Panchalingam, K, Rapoport, A et al. Increased cerebrospinal fluid glutamine levels in depressed patients. Biol Psychiatry. 2000; 47(7): 586–593.Google Scholar
Hashimoto, K, Sawa, A, Iyo, M. Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry. 2007; 62(11): 1310–1316.Google Scholar
Frye, MA, Tsai, GE, Huggins, T, Coyle, JT, Post, RM. Low cerebrospinal fluid glutamate and glycine in refractory affective disorder. Biol Psychiatry. 2007; 61(2): 162–166.Google Scholar
Gerner, RH, Fairbanks, L, Anderson, GM, et al. CSF neurochemistry in depressed, manic, and schizophrenic patients compared with that of normal controls. Am J Psychiatry. 1984; 141(12): 1533–1540.Google Scholar
Berrettini, WH, Nurnberger, JI, Hare, TA, Simmons-Alling, S, Gershon, ES. CSF GABA in euthymic manic-depressive patients and controls. Biol Psychiatry. 1986; 21(8–9): 844–846.CrossRefGoogle ScholarPubMed
Rajkowska, G. Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry. 2000; 48(8): 766–777.Google Scholar
Trullas, R, Skolnick, P. Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur J Pharmacol. 1990; 185(1): 1–10.Google Scholar
Berman, RM, Cappiello, A, Anand, A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000; 47(4): 351–354.Google Scholar
Mathew, SJ, Shah, A, Lapidus, K, et al. Ketamine for treatment-resistant unipolar depression: Current evidence. CNS Drugs. 2012; 26(3): 189–204.CrossRefGoogle ScholarPubMed
Zarate, CA, Brutsche, NE, Ibrahim, L, et al. Replication of ketamine’s antidepressant efficacy in bipolar depression: A randomized controlled add-on trial. Biol Psychiatry. 2012; 71(11): 939–946.Google Scholar
Govindaraju, V, Young, K, Maudsley, AA. Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed. 2000; 13(3): 129–153.Google Scholar
Hashimoto, R, Hough, C, Nakazawa, T, Yamamoto, T, Chuang, D-M. Lithium protection against glutamate excitotoxicity in rat cerebral cortical neurons: Involvement of NMDA receptor inhibition possibly by decreasing NR2B tyrosine phosphorylation. J Neurochem. 2002; 80(4): 589–597.Google Scholar
Kumar, A, Singh, RL, Babu, GN. Cell death mechanisms in the early stages of acute glutamate neurotoxicity. Neurosci Res. 2010; 66(3): 271–278.Google Scholar
Gigante, AD, Young, LT, Yatham, LN, et al. Morphometric post-mortem studies in bipolar disorder: Possible association with oxidative stress and apoptosis. Int J Neuropsychopharmacol. 2011; 14(8): 1075–1089.CrossRefGoogle ScholarPubMed
Martinez-Hernandez, A, Bell, KP, Norenberg, MD. Glutamine synthetase: Glial localization in brain. Science. 1977; 195(4284): 1356–1358.Google Scholar
Waagepetersen, HS, Sonnewald, U, Schousboe, A. Glutamine, Glutamate, and GABA: metabolic aspects. In: Lajtha, A, Oja, S, Schousboe, A, Saransaari, P, editors. Handbook of Neurochemistry and Molecular Neurobiology: Amino Acids and Peptides in the Nervous System. New York: Springer; 2007, pp. 1–21.Google Scholar
Rothman, DL, De Feyter, HM, de Graaf, RA, Mason, GF, Behar, KL. 13 C MRS studies of neuroenergetics and neurotransmitter cycling in humans. NMR Biomed. 2011; 24(8): 943–957.Google Scholar
Daikhin, Y, Yudkoff, M. Compartmentation of brain glutamate metabolism in neurons and glia. J Nutr. 2000; 130(4S Suppl): 1026S–1031S.Google Scholar
Brennan, BP, Hudson, JI, Jensen, JE, et al. Rapid enhancement of glutamatergic neurotransmission in bipolar depression following treatment with riluzole. Neuropsychopharmacology. 2010; 35(3): 834–846.Google Scholar
Soeiro de Souza, MG, Henning, A, Machado-Vieira, R, et al. Anterior cingulate Glutamate-Glutamine cycle metabolites are altered in euthymic bipolar I disorder. Eur Neuropsychopharmacol. 2015; 25(12): 2221–2229.CrossRefGoogle ScholarPubMed
Igarashi, H, Kwee, IL, Nakada, T, Katayama, Y, Terashi, A. 1 H magnetic resonance spectroscopic imaging of permanent focal cerebral ischemia in rat: Longitudinal metabolic changes in ischemic core and rim. Brain Res. 2001; 907(1–2): 208–221.Google Scholar
Iltis, I, Koski, DM, Eberly, LE, et al. Neurochemical changes in the rat prefrontal cortex following acute phencyclidine treatment: An in vivo localized (1)H MRS study. NMR Biomed. 2009; 22(7): 737–744.Google Scholar
Mlynárik, V, Kohler, I, Gambarota, G, et al. Quantitative proton spectroscopic imaging of the neurochemical profile in rat brain with microliter resolution at ultra-short echo times. Magn Reson Med. 2008; 59(1): 52–58.CrossRefGoogle ScholarPubMed
Ongur, D, Jensen, JE, Prescot, AP, et al. Abnormal glutamatergic neurotransmission and neuronal-glial interactions in acute mania. Biol Psychiatry. 2008; 64(8): 718–726.Google Scholar
Théberge, J, Bartha, R, Drost, DJ, et al. Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Am J Psychiatry. 2002; 159(11): 1944–1946.Google Scholar
Théberge, J, Al-Semaan, Y, Williamson, PC, et al. 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. 2003; 160(12): 2231–2233.Google Scholar
Erlander, MG, Tillakaratne, NJ, Feldblum, S, Patel, N, Tobin, AJ. Two genes encode distinct glutamate decarboxylases. Neuron. 1991; 7(1): 91–100.Google Scholar
Bu, DF, Erlander, MG, Hitz, BC, et al. Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene. Proc Natl Acad Sci USA. 1992; 89(6): 2115–2119.Google Scholar
Guidotti, A, Auta, J, Davis, JM, et al. Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study. Arch Gen Psychiatry. 2000; 57(11): 1061–1069.Google Scholar
Heckers, S, Stone, D, Walsh, J, et al. Differential hippocampal expression of glutamic acid decarboxylase 65 and 67 messenger RNA in bipolar disorder and schizophrenia. Arch Gen Psychiatry. 2002; 59(6): 521–529.Google Scholar
Woo, T-UW, Walsh, JP, Benes, FM. Density of glutamic acid decarboxylase 67 messenger RNA-containing neurons that express the N-methyl-D-aspartate receptor subunit NR2A in the anterior cingulate cortex in schizophrenia and bipolar disorder. Arch Gen Psychiatry. 2004; 61(7): 649–657.Google Scholar
Thompson, M, Weickert, CS, Wyatt, E, Webster, MJ. Decreased glutamic acid decarboxylase(67) mRNA expression in multiple brain areas of patients with schizophrenia and mood disorders. J Psychiatr Res. 2009; 43(11): 970–977.Google Scholar
Maddock, RJ, Buonocore, MH. MR spectroscopic studies of the brain in psychiatric disorders. Curr Top Behav Neurosci. 2012; 11: 199–251.Google Scholar
Cooper, AJL, Jeitner, TM. Central role of glutamate metabolism in the maintenance of nitrogen homeostasis in normal and hyperammonemic brain. Biomolecules. 2016 March 26; 6(2): 16.Google Scholar
Walls, AB, Waagepetersen, HS, Bak, LK, Schousboe, A, Sonnewald, U. The glutamine-glutamate/GABA cycle: Function, regional differences in glutamate and GABA production and effects of interference with GABA metabolism. Neurochem Res. 2015; 40(2): 402–409.Google Scholar
Buonocore, MH, Maddock, RJ. Magnetic resonance spectroscopy of the brain: A review of physical principles and technical methods. Rev Neurosci. 2015; 26(6): 609–632.Google Scholar
Bush, G, Luu, P, Posner, M. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci (Regul Ed). 2000; 4(6): 215–222.Google Scholar
Strakowski, SM, Adler, CM, Almeida, J, et al. The functional neuroanatomy of bipolar disorder: A consensus model. Bipolar Disord. 2012 June; 14(4): 313–325. DOI:10.1111/j.1399-5618.2012.01022.x.Google Scholar
Drevets, WC, Price, JL, Simpson, JR, et al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature. 1997; 386(6627): 824–827.CrossRefGoogle ScholarPubMed
Haldane, M, Frangou, S. New insights help define the pathophysiology of bipolar affective disorder: Neuroimaging and neuropathology findings. Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28(6): 943–960.Google Scholar
Savitz, JB, Price, JL, Drevets, WC. Neuropathological and neuromorphometric abnormalities in bipolar disorder: View from the medial prefrontal cortical network. Neurosci Biobehav Rev. 2014; 42: 132–147.CrossRefGoogle ScholarPubMed
Drevets, WC, Savitz, J, Trimble, M. The subgenual anterior cingulate cortex in mood disorders. CNS Spectr. 2008; 13(8): 663–681.Google Scholar
Hibar, DP, Westlye, LT, Doan, NT, et al. Cortical abnormalities in bipolar disorder: An MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group. Mol Psychiatry. 2018 April; 23(4): 932–942.Google Scholar
McGirr, A, Berlim, MT, Bond, DJ, et al. A systematic review and meta-analysis of randomized controlled trials of adjunctive ketamine in electroconvulsive therapy: Efficacy and tolerability. J Psychiatr Res. 2015; 62: 23–30.Google Scholar
Godfrey, KEM, Gardner, AC, Kwon, S, Chea, W, Muthukumaraswamy, SD. Differences in excitatory and inhibitory neurotransmitter levels between depressed patients and healthy controls: A systematic review and meta-analysis. J Psychiatr Res. 2018; 105: 33–44.Google Scholar
Moriguchi, S, Takamiya, A, Noda, Y, et al. Glutamatergic neurometabolite levels in major depressive disorder: A systematic review and meta-analysis of proton magnetic resonance spectroscopy studies. Mol Psychiatry. 2019; 24: 952–964.Google Scholar
Arnone, D, Mumuni, AN, Jauhar, S, Condon, B, Cavanagh, J. Indirect evidence of selective glial involvement in glutamate-based mechanisms of mood regulation in depression: Meta-analysis of absolute prefrontal neuro-metabolic concentrations. Eur Neuropsychopharmacol. 2015; 25(8): 1109–1117.Google Scholar
Luykx, JJ, Laban, KG, van den Heuvel, MP, et al. Region and state specific glutamate downregulation in major depressive disorder: A meta-analysis of (1)H-MRS findings. Neurosci Biobehav Rev. 2012; 36(1): 198–205.Google Scholar
Dager, SR, Friedman, SD, Parow, A, et al. Brain metabolic alterations in medication-free patients with bipolar disorder. Arch Gen Psychiatry. 2004; 61(5): 450–458.Google Scholar
Frye, MA, Watzl, J, Banakar, S, et al. Increased anterior cingulate/medial prefrontal cortical glutamate and creatine in bipolar depression. Neuropsychopharmacology. 2007; 32(12): 2490–2499.Google Scholar
Soeiro de Souza, MG, Salvadore, G, Moreno, RA, et al. Bcl-2 rs956572 polymorphism is associated with increased anterior cingulate cortical glutamate in euthymic bipolar I disorder. Neuropsychopharmacology. 2013; 38(3): 468–475.Google Scholar
Ehrlich, A, Schubert, F, Pehrs, C, Gallinat, J. Alterations of cerebral glutamate in the euthymic state of patients with bipolar disorder. Psychiatry Res. 2015; 233(2): 73–80.Google Scholar
Kubo, H, Nakataki, M, Sumitani, S, et al. 1 H-magnetic resonance spectroscopy study of glutamate-related abnormality in bipolar disorder. J Affect Disord. 2017; 208: 139–144.Google Scholar
Soeiro de Souza, MG, Otaduy, MCG, Machado-Vieira, R, et al. Anterior cingulate cortex glutamatergic metabolites and mood stabilizers in euthymic bipolar I disorder patients: A proton magnetic resonance spectroscopy study. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 December; 3(12): 985–991.Google Scholar
Michael, N, Erfurth, A, Ohrmann, P, et al. Metabolic changes within the left dorsolateral prefrontal cortex occurring with electroconvulsive therapy in patients with treatment resistant unipolar depression. Psychol Med. 2003; 33(7): 1277–1284.Google Scholar
Bhagwagar, Z, Wylezinska, M, Jezzard, P, et al. Reduction in occipital cortex gamma-aminobutyric acid concentrations in medication-free recovered unipolar depressed and bipolar subjects. Biol Psychiatry. 2007; 61(6): 806–812.Google Scholar
Yildiz-Yesiloglu, A, Ankerst, DP. 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. 2006; 30(6): 969–995.Google Scholar
Gigante, AD, Bond, DJ, Lafer, B, et al. Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: A meta-analysis. Bipolar Disord. 2012; 14(5): 478–487.Google Scholar
Chitty, KM, Lagopoulos, J, Lee, RSC, Hickie, IB, Hermens, DF. A systematic review and meta-analysis of proton magnetic resonance spectroscopy and mismatch negativity in bipolar disorder. Eur Neuropsychopharmacol. 2013; 23(11): 1348–1363.Google Scholar
Drevets, WC. Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression. Prog Brain Res. 2000; 126: 413–431.Google Scholar
Phillips, ML, Drevets, WC, Rauch, SL, Lane, R. Neurobiology of emotion perception I: The neural basis of normal emotion perception. Biol Psychiatry. 2003; 54(5): 504–514.CrossRefGoogle ScholarPubMed
Anticevic, A, Savic, A, Repovs, G, et al. Ventral anterior cingulate connectivity distinguished nonpsychotic bipolar illness from psychotic bipolar disorder and schizophrenia. Schizophr Bull. 2015; 41(1): 133–143.Google Scholar
Liu, J, Blond, BN, van Dyck, LI, et al. Trait and state corticostriatal dysfunction in bipolar disorder during emotional face processing. Bipolar Disord. 2012; 14(4): 432–441.Google Scholar
Foland-Ross, LC, Thompson, PM, Sugar, CA, et al. Investigation of cortical thickness abnormalities in lithium-free adults with bipolar I disorder using cortical pattern matching. Am J Psychiatry. 2011; 168(5): 530–539.Google Scholar
Patel, NC, DelBello, MP, Cecil, KM, et al. Temporal change in N-acetyl-aspartate concentrations in adolescents with bipolar depression treated with lithium. J Child Adolesc Psychopharmacol. 2008; 18(2): 132–139.Google Scholar
Colla, M, Schubert, F, Bubner, M, et al. 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. 2009; 14(7): 696–704, 647.Google Scholar
Senaratne, R, Milne, AM, MacQueen, GM, Hall, GBC. Increased choline-containing compounds in the orbitofrontal cortex and hippocampus in euthymic patients with bipolar disorder: A proton magnetic resonance spectroscopy study. Psychiatry Res. 2009; 172(3): 205–209.Google Scholar
Moore, CM, Frazier, JA, Glod, CA, et al. Glutamine and glutamate levels in children and adolescents with bipolar disorder: A 4.0-T proton magnetic resonance spectroscopy study of the anterior cingulate cortex. J Am Acad Child Adolesc Psychiatry. 2007; 46(4): 524–534.Google Scholar
Friedman, SD, Dager, SR, Parow, A, et al. Lithium and valproic acid treatment effects on brain chemistry in bipolar disorder. Biol Psychiatry. 2004; 56(5): 340–348.Google Scholar
Machado-Vieira, R, Gattaz, WF, Zanetti, MV, et al. A longitudinal (6-week) 3 T (1)H-MRS study on the effects of lithium treatment on anterior cingulate cortex metabolites in bipolar depression. Eur Neuropsychopharmacol. 2015; 25(12): 2311–2317.Google Scholar
Zanetti, MV, Otaduy, MC, de Sousa, RT, et al. Bimodal effect of lithium plasma levels on hippocampal glutamate concentrations in bipolar II depression: A pilot study. Int J Neuropsychopharmacol. 2014 October 31; 18(6): pyu058.Google Scholar
O’Donnell, T, Rotzinger, S, Nakashima, TT, et al. Chronic lithium and sodium valproate both decrease the concentration of myo-inositol and increase the concentration of inositol monophosphates in rat brain. Brain Res. 2000; 880(1–2): 84–91.Google Scholar
Szulc, A, Wiedlocha, M, Waszkiewicz, N, et al. Proton magnetic resonance spectroscopy changes after lithium treatment. Systematic review. Psychiatry Res Neuroimaging. 2018; 273: 1–8.Google Scholar
Luscher, B, Shen, Q, Sahir, N. The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry. 2011; 16(4): 383–406.Google Scholar
Petty, F, Schlesser, MA. Plasma GABA in affective illness. A Preliminary Investigation. J Affect Disord. 1981; 3(4): 339–343.Google Scholar
Petty, F, Sherman, AD. Plasma GABA levels in psychiatric illness. J Affect Disord. 1984; 6(2): 131–138.Google Scholar
Gerner, RH, Hare, TA. CSF GABA in normal subjects and patients with depression, schizophrenia, mania, and anorexia nervosa. Am J Psychiatry. 1981; 138(8): 1098–1101.Google Scholar
Honig, A, Bartlett, JR, Bouras, N, Bridges, PK. Amino acid levels in depression: A preliminary investigation. J Psychiatr Res. 1988; 22(3): 159–164.Google Scholar
Chiapponi, C, Piras, F, Piras, F, Caltagirone, C, Spalletta, G. GABA system in schizophrenia and mood disorders: A mini review on third-generation imaging studies. Front Psychiatry. 2016; 7: 61.Google Scholar
Schür, RR, Draisma, LWR, Wijnen, JP, et al. Brain GABA levels across psychiatric disorders: A systematic literature review and meta-analysis of (1) H-MRS studies. Hum Brain Mapp. 2016; 37(9): 3337–3352.Google Scholar
Romeo, B, Choucha, W, Fossati, P, Rotge, J-Y. Meta-analysis of central and peripheral γ-aminobutyric acid levels in patients with unipolar and bipolar depression. J Psychiatry Neurosci. 2018; 43(1): 58–66.Google Scholar
Kalueff, AV, Nutt, DJ. Role of GABA in anxiety and depression. Depress Anxiety. 2007; 24(7): 495–517.Google Scholar
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; 159(4): 663–665.Google Scholar
Sanacora, G, Mason, GF, Rothman, DL, et al. Increased cortical GABA concentrations in depressed patients receiving ECT. Am J Psychiatry. 2003; 160(3): 577–579.CrossRefGoogle ScholarPubMed
Verkuyl, JM, Hemby, SE, Joëls, M. Chronic stress attenuates GABAergic inhibition and alters gene expression of parvocellular neurons in rat hypothalamus. Eur J Neurosci. 2004; 20(6): 1665–1673.Google Scholar
Wang, PW, Sailasuta, N, Chandler, RA, Ketter, TA. Magnetic resonance spectroscopy measurement of cerebral gamma-aminobutyric acid concentrations in patients with bipolar disorders. Acta Neuropsychiatrica. 2006; 18: 120–126.Google Scholar
Kaufman, RE, Ostacher, MJ, Marks, EH, et al. Brain GABA levels in patients with bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33(3): 427–434.CrossRefGoogle ScholarPubMed
Godlewska, BR, Yip, SW, Near, J, Goodwin, GM, Cowen, PJ. Cortical glutathione levels in young people with bipolar disorder: A pilot study using magnetic resonance spectroscopy. Psychopharmacology (Berl). 2014; 231(2): 327–332.Google Scholar
Prisciandaro, JJ, Tolliver, BK, Prescot, AP, et al. Unique prefrontal GABA and glutamate disturbances in co-occurring bipolar disorder and alcohol dependence. Transl Psychiatry. 2017; 7(7): e1163.Google Scholar
Levy, LM, Degnan, AJ. GABA-based evaluation of neurologic conditions: MR spectroscopy. AJNR Am J Neuroradiol. 2013; 34(2): 259–265.Google Scholar
Mesdjian, E, Ciesielski, L, Valli, M, et al. Sodium valproate: Kinetic profile and effects on GABA levels in various brain areas of the rat. Prog Neuropsychopharmacol Biol Psychiatry. 1982; 6(3): 223–233.Google Scholar
Rubenstein, JLR, Merzenich, MM. Model of autism: Increased ratio of excitation/inhibition in key neural systems. Genes Brain Behav. 2003; 2(5): 255–267.CrossRefGoogle ScholarPubMed
Krystal, JH, Sanacora, G, Blumberg, H, et al. Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Mol Psychiatry. 2002; 7(Suppl 1): S71–80.Google Scholar
Lener, MS, Niciu, MJ, Ballard, ED, et al. Glutamate and gamma-aminobutyric acid systems in the pathophysiology of major depression and antidepressant response to ketamine. Biol Psychiatry. 2017; 81(10): 886–897.Google Scholar
Soeiro de Souza, MG, Machado-Vieira, R, Soares, Bio D, Do Prado, CM, Moreno, RA. COMT polymorphisms as predictors of cognitive dysfunction during manic and mixed episodes in bipolar I disorder. Bipolar Disord. 2012; 14(5): 554–564.Google Scholar
Michael, N, Erfurth, A, Ohrmann, P, et al. Acute mania is accompanied by elevated glutamate/glutamine levels within the left dorsolateral prefrontal cortex. Psychopharmacology (Berl). 2003; 168(3): 344–346.Google Scholar
Hajek, T, Bernier, D, Slaney, C, et al. A comparison of affected and unaffected relatives of patients with bipolar disorder using proton magnetic resonance spectroscopy. J Psychiatry Neurosci. 2008; 33(6): 531–540.Google Scholar

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