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January 1982, Vol 39, No. 1 >
Article | January 1982

CSF Levels of γ-Aminobutyric Acid in Schizophrenia: Title and subTitle BreakLow Values in Recently Ill Patients

Daniël P. van Kammen, MD, PhD; David E. Sternberg, MD; Theodore A. Hare, PhD; Robert N. Waters, MD; William E. Bunney, Jr, MD
[+] Author Affiliations

Accepted for publication July 20, 1981.

Read in part before the XII Collegium Internationale Neuropharmacologicum, Götenburg, Sweden, June 24, 1980.

Reprint requests to National Institute of Mental Health, Bldg 10, Room 4N214, 9000 Rockville Pike, Bethesda, MD 20205 (Dr van Kammen).


Arch Gen Psychiatry. 1982;39(1):91-97. doi:10.1001/archpsyc.1982.04290010065012
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References
Comments

• γ-Aminobutyric acid (GABA) levels in CSF were not significantly different in 30 drug-free schizophrenic patients and in 39 normal control subjects, because the control subjects were significantly older. Schizophrenic women had significantly lower levels than age-matched normal control women (< 30 years). The GABA levels increased with duration of illness, number of hospitalizations, and months of hospitalizations, as well as with age. They correlated nonsignificantly with psychosis levels. After short-term pimozide treatment, GABA levels in all patients were raised, albeit nonsignificantly. The data suggest that low GABA levels may be observed only in the early years of the illness, particularly in female schizophrenic patients, and that these levels increase with time and with long-term neuroleptic treatment.

REFERENCES

1 +
Roberts E, Frankel S:  γ-Aminobutyric acid in the brain . Fed Proc 1950;;9:219.
2 +
Awapara J:  Detection and identification of metabolites in tissues by means of paper chromatography . Fed Proc 1950;;9:148.
3 +
Baxter C:  Some recent advances in studies of GABA metabolism and compartmentation , in Roberts E, Chase TN, Tower DB (eds): GABA in Nervous System Function . New York, Raven Press, 1976;, pp 61-87.
4 +
Snyder SH:  Neurotransmitter and drug receptors in the brain . Biochem Pharmacol 1975;;24:1371-1374.
5 +
Tallman JF, Paul SM, Skolnick P, et al:  Receptors for the age of anxiety: Pharmacology of the benzodiazepines . Science 1980;;207:274-281.
6 +
Enna SJ, Bennett JP Jr, Bylund DB, et al:  Neurotransmitter receptor binding: Regional distribution in human brain . J Neurochem 1977;;28:233-236.
7 +
Vogel WH, Heginbothom SD, Boehme DH:  Glutamic acid decarboxylase, glutamine synthetase and glutamic acid dehydrogenase in various areas of human brain . Brain Res 1975;;88:131-135.
8 +
Kim JS, Bak IJ, Hassler R, et al:  Role of gamma-aminobutyric acid (GABA) in the extrapyramidal motor system: II. Some evidence for the existence of a type of GABA-rich strio-nigral neurons . Exp Brain Res 1971;;14:95-104.
9 +
Yoshida M, Precht W:  Monosynaptic inhibition of neurons of the substantia nigra by caudato-nigral fibers . Brain Res 1971;;32:225-228.
10 +
Fuxe K, Perez de la Mora M, Hökfelt T, et al:  GABA-DA interactions and their possible relation to schizophrenia , in Shagass C, Gershon S, Friedhoff AJ (eds): Psychopathology and Brain Dysfunction . New York, Raven Press, 1977;, pp 97-111.
11 +
Stevens JR:  An anatomy of schizophrenia . Arch Gen Psychiatry 1973;;29:177-189.
12 +
Van Kammen DP:  The dopamine hypothesis of schizophrenia revisited . Psychoneuroendocrinology 1979;;4:37-46.
13 +
Stevens JR, Wilson K, Foote W:  GABA blockade, dopamine and schizophrenia: Experimental studies in the cat . Psychopharmacologia 1974;;39:105-119.
14 +
Roberts E:  An hypothesis suggesting that there is a deficit in the GABA system in schizophrenia . Neurosci Res Program Bull 1972;;10:468-483.
15 +
Roberts E:  Disinhibition as an organizing principle in the nervous system—the role of the GABA system: Application to neurologic and psychiatric disorders , in Roberts E, Chase TN, Tower DB (eds): GABA in Nervous System Function . New York, Raven Press, 1976;, pp 515-539.
16 +
Van Kammen DP:  γ-Aminobutyric acid (GABA) and the dopamine hypothesis of schizophrenia . Am J Psychiatry 1977;;134:138-143.
17 +
Glaeser BS, Hare TA:  Measurement of GABA in human cerebrospinal fluid . Biochem Med 1975;;12:274-282.
18 +
Langer DH, Brown GLV, Bunney WE Jr, et al:  Gamma-aminobutyric acid in CSF in schizophrenia . N Engl J Med 1975;;293:201.
19 +
Huizinga JA, Teelken AW, Muskiet FAJ, et al:  Identification of GABA in human CSF bv gas liquid chromatography and mass spectrometry . N Engl J Med 1977;;296:692.
20 +
Enna SJ, Wood JH, Snyder SH:  Gamma-aminobutyric acid (GABA) in human cerebrospinal fluid: Radioreceptor assay . J Neurochem 1977;;28:1121-1124.
21 +
Enna SJ, Ziegler MG, Lake CR, et al:  CSF GABA: Correlation with CSF and blood constituents and alteration in neurological disorders , in Wood JH (ed): Neurobiology of Cerebrospinal Fluid . New York, Plenum Press, 1980;, vol 1, pp 189-196.
22 +
Faull KF, DoAmaral JR, Berger PA, et al:  Mass spectrometric identification and selected ion monitoring quantitation of gamma-aminobutyric acid (GABA) in human lumbar cerebrospinal fluid . J Neurochem 1978;;31:1119-1122.
23 +
Neethling AC, McCarthy B, Taljaard JJF:  Gamma-aminobutyric acid in CSF . Lancet 1980;;1:211.
24 +
Manyam NVB, Katz L, Hare T, et al:  Levels of gamma-aminobutyric acid in cerebrospinal fluid in various neurologic disorders . Arch Neurol 1980;;37:352-355.
25 +
Wood JH, Hare TA, Enna SJ, et al:  Sites of origin and rostrocaudal concentration gradients of GABA in cerebrospinal fluid . Brain Res 1980;;5:111-114.
26 +
Hare TA, Wood JH, Manyam NVB:  Selection of control populations for clinical cerebrospinal fluid GABA investigations based on comparison with normal volunteers . Brain Res 1980;;5:721-724.
27 +
Van Kammen DP, Sternberg DE:  CSF studies in schizophrenia , in Wood JH (ed): The Neurobiology of Spinal Fluid . New York, Plenum Press, 1980;, vol 1, pp 719-749.
28 +
Cross AJ, Crow TJ, Owen F:  Gamma-aminobutyric acid in the brain in schizophrenia . Lancet 1979;;1:560-561.
29 +
Perry TL, Buchanan J, Kish SJ, et al:  γ-Aminobutyric acid deficiency in brain of schizophrenic patients . Lancet . 1979;;1:237.
30 +
Iversen LL, Bird E, Spokes E, et al:  Agonist specificity of GABA binding sites in human brain and GABA in Huntington 's disease and schizophrenia , in Krogsgaard-Larsen P, Scheel-Krüger J, Kofod H (eds): GABA-Neuro-transmitters: Pharmacochemical, Biochemical and Pharmacological Aspects . New York, Academic Press Inc, 1979;, pp 177-190.
31 +
Bennett JP, Enna SJ, Bylund DB, et al:  Neurotransmitter receptors in frontal cortex of schizophrenics . Arch Gen Psychiatry 1979;;36:927-934.
32 +
White HL, Davidson JRT, Miller RD, et al:  Platelet gamma-aminobutyrate-α-ketoglutarate transaminase (GABA-T) in schizophrenia . Am J Psychiatry 1980;;137:733-734.
33 +
Zander KJ, Fischer B, Zimmer R, et al:  Long-term neuroleptic treatment of schizophrenic patients: Clinical and biochemical effects of withdrawal . Psychopharmacology 1981;;73:43-47.
34 +
McCarthy BW, Gomes UR, Neethling AC, et al:  Gamma-aminobutyric acid concentration in cerebrospinal fluid in schizophrenia . J Neurochem 1981;;36:1406-1408.
35 +
Van Kammen DP, Sternberg DE, Hare TA, et al:  Spinal fluid GABA levels in schizophrenia , in Angrist B, Burrows GD, Lader M, et al (eds): Biochemistry of the Human Cerebrospinal Fluid, vol 31, in Advances in the Bio-Sciences . New York, Pergamon Press, 1981;, pp 315-321.
36 +
Lichtshtein D, Dobkin J, Ebstein RP, et al:  Gamma-aminobutyric acid (GABA) in the CSF of schizophrenic patients before and after neuroleptic treatment . Br J Psychiatry 1978;;132:145-148.
37 +
Gold BI, Bowers MB, Roth RH, et al:  GABA levels in CSF of patients with psychiatric disorders . Am J Psychiatry 1980;;137:362-364.
38 +
Bowers MB, Gold BI, Roth RH:  CSF GABA in psychotic disorders . Psychopharmacology 1980;;70:279-282.
39 +
Gerner RH, Hare TA:  CSF GABA in normals, depression, schizophrenia, mania and anorexia nervosa . Am J Psychiatry 1981;;138:1098-1101.
40 +
Cattabeni F, Maggi A, Monduzzi M:  GABA: Circadian fluctuations in rat hypothalamus . J Neurochem 1978;;31:565-567.
41 +
Wood JH:  Neurochemical analysis of cerebrospinal fluid . Neurology 1980;;30:645-651.
42 +
Costa E, Cheney DL, Mao CC, et al:  Action of antischizophrenic drugs on the metabolism of gamma-aminobutyric acid and acetylcholine in globus pallidus, striatum and n accumbens . Fed Proc 1978;;37:2408-2414.
43 +
Fjalland B:  Inhibition by neuroleptics of uptake of 3H-GABA into rat brain synaptosomes . Acta Pharmacol Toxicol 1978;;42:73-76.
44 +
Lloyd KG, Hornykiewicz 0:  Effect of chronic neuroleptic of L-DOPA administration on GABA levels in the rat substantia nigra . Life Sci 1977;;21:1489-1496.
45 +
Perry TL, Hansen S, Kish SJ:  Effects of chronic administration of antipsychotic drugs on GABA and other amino acids in the mesolimbic area of rat brain . Life Sci 1979;;24:283-288.
46 +
Pinder RM, Brogden RM, Sawyer PR, et al:  Pimozide: A review of its pharmacological properties and therapeutic uses in psychiatry . Drugs 1976;;12:1-40.
47 +
Spitzer RL, Endicott J, Robins E: Research Diagnostic Criteria for a Selected Group of Functional Disorders . New York, Biometrics Research Division, New York State Psychiatric Institute, 1978;.
48 +
Carpenter WT, Strauss JS, Bartko JJ:  Flexible system for the diagnosis of schizophrenia: Report from the WHO International Pilot Study of Schizophrenia . Science 1973;;182:1275-1278.
49 +
Hare TH, Wood JH, Ballenger JC, et al:  Gamma-aminobutyric acid in human cerebrospinal fluid: Normal values . Lancet 1979;;2:534-535.
50 +
Phillips L:  Case history data and prognosis in schizophrenia . J Nerv Ment Dis 1953;;117:515-525.
51 +
Gochman N, Schmitz JM:  Application of a new peroxidase indicator reaction to the specific, automated determination of glucose with glucose oxidase . Clin Chem 1972;;18:943-950.
52 +
Bunney WE, Hamburg DA:  Methods for reliable longitudinal observation of behavior . Arch Gen Psychiatry 1963;;9:280-294.
53 +
Hare TA, Manyam NVB:  Rapid and sensitive ion exchange/fluorometric method for measuring GABA on physiological fluids . Anal Biochem 1980;;101:349-355.
54 +
Bowers MB Jr, Heninger GR, Sternberg D:  Clinical processes and central dopaminergic activity in psychotic disorders . Commun Psychopharmacol 1980;;4:177-188.
55 +
McKhann GM, Albers RW, Sokoloff L, et al:  The quantitative significance of the gamma-aminobutyric acid pathway in cerebral oxidative metabolism , in Roberts E, Baster CF, van Harreveld A, et al (eds): Inhibition in the Nervous System and Gamma-Aminobutyric Acid . New York, Pergamon Press, 1960;, pp 169-181.
56 +
Gibson GE, Peterson C, Sansone J: Hypoxia decreases the metabolism of the glucose-derived neurotransmitters. Read before the tenth annual meeting of the Society for Neurosciences, Cincinnati, Nov 9, 1980.
57 +
Grace AA, Bunney BS:  Paradoxical GABA excitation of nigral dopaminergic cells: Indirect mediation through reticulata inhibitory neurons . Eur J Pharmacol 1979;;59:211-218.
58 +
Waszczak BL, Walters JR:  Intravenous GABA agonist administration stimulates firing of A10 dopaminergic neurons . Eur J Pharmacol 1980;;66:141-144.
59 +
Arnt J, Scheel-Krüger J:  GABAergic and glycinergic mechanisms within the substantia nigra: Pharmacological specificity of dopamineindependent contralateral turning behavior and interactions with other neurotransmitters . Psychopharmacology 1979;;62:267-277.
60 +
Van der Heyden JAM, Venema K, Korf J:  Biphasic and opposite effects of dopamine and apomorphine on endogenous GABA release in the rat substantia nigra . J Neurochem 1980;;34:119-125.
61 +
Crow TJ:  Molecular pathology of schizophrenia: More than one disease process? Br Med J 1980;;280:66-68.
62 +
Simeon J, Fink M, Itil TM, et al:  d-Cycloserine therapy on psychosis by symptom provocation . Comp Psychiatry 1970;;11:80-88.
63 +
Tamminga CA, Crayton JW, Chase TN:  Muscimol: GABA agonist therapy in schizophrenia . Am J Psychiatry 1978;;135:746-747.
64 +
Schulz SC, van Kammen DP, Buchsbaum MS, et al:  Gamma-hydroxybutyrate treatment of schizophrenia: A pilot study . Pharmacopsychiatry 1981;;14:129-134.
65 +
Simpson GM, Branchex MM, Shrivastava RK:  Baclofen in schizophrenia . Lancet 1975;;1:966-967.
66 +
Bartholini G, Cuche H, Zarifian E, et al:  Involvement of cholinergic and GABAergic systems in schizophrenia , in Obiol J, Ballus C, Gonzalesmonclus E, et al (eds): Biological Psychiatry Today . Amsterdam, Elsevier North Holland Biomédical Press, 1979;, pp 439-444.
67 +
Bartholini G, Scatton B, Zivkovic B, et al:  On the mode of action of SL 76002, a new GABA receptor agonist , in Krogsgaard-Larsen P, Scheel Krüger J, Kofod H (eds): GABA-Neurotransmitters , Alfred Benson Symposium Series, vol 12. New York, Academic Press Inc, 1979;, pp 326-339.
68 +
Linnoila M, Viukari M, Hietala O:  Effect of sodium valproate on tardive dyskinesia . Br J Psychiatry 1976;;129:114-119.
69 +
Casey DE, Gerlach J, Magelund G, et al:  Gamma-acetylenic GABA in tardive dyskinesia . Arch Gen Psychiatry 1980;;37:1376-1379.
70 +
Enna SJ, Maggi A:  Minireview: Biochemical pharmacology of GABAergic agonists . Life Sci 1979;;24:1727-1738.
71 +
Bunney BS, Aghajanian GK:  The effect of antipsychotic drugs on the firing of dopaminergic neurons: A reappraisal , in Sedval G (ed): Antipsychotic Drugs: Pharmacodynamics and Pharmacokinetics . New York, Pergamon Press, 1975;, pp 305-318.
72 +
Jimerson D, van Kammen DP, Post RM, et al: Diazepam in schizophrenia: A double-blind trial. Am J Psychiatry, to be published.

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Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Roberts E, Frankel S:  γ-Aminobutyric acid in the brain . Fed Proc 1950;;9:219.
2 +
Awapara J:  Detection and identification of metabolites in tissues by means of paper chromatography . Fed Proc 1950;;9:148.
3 +
Baxter C:  Some recent advances in studies of GABA metabolism and compartmentation , in Roberts E, Chase TN, Tower DB (eds): GABA in Nervous System Function . New York, Raven Press, 1976;, pp 61-87.
4 +
Snyder SH:  Neurotransmitter and drug receptors in the brain . Biochem Pharmacol 1975;;24:1371-1374.
5 +
Tallman JF, Paul SM, Skolnick P, et al:  Receptors for the age of anxiety: Pharmacology of the benzodiazepines . Science 1980;;207:274-281.
6 +
Enna SJ, Bennett JP Jr, Bylund DB, et al:  Neurotransmitter receptor binding: Regional distribution in human brain . J Neurochem 1977;;28:233-236.
7 +
Vogel WH, Heginbothom SD, Boehme DH:  Glutamic acid decarboxylase, glutamine synthetase and glutamic acid dehydrogenase in various areas of human brain . Brain Res 1975;;88:131-135.
8 +
Kim JS, Bak IJ, Hassler R, et al:  Role of gamma-aminobutyric acid (GABA) in the extrapyramidal motor system: II. Some evidence for the existence of a type of GABA-rich strio-nigral neurons . Exp Brain Res 1971;;14:95-104.
9 +
Yoshida M, Precht W:  Monosynaptic inhibition of neurons of the substantia nigra by caudato-nigral fibers . Brain Res 1971;;32:225-228.
10 +
Fuxe K, Perez de la Mora M, Hökfelt T, et al:  GABA-DA interactions and their possible relation to schizophrenia , in Shagass C, Gershon S, Friedhoff AJ (eds): Psychopathology and Brain Dysfunction . New York, Raven Press, 1977;, pp 97-111.
11 +
Stevens JR:  An anatomy of schizophrenia . Arch Gen Psychiatry 1973;;29:177-189.
12 +
Van Kammen DP:  The dopamine hypothesis of schizophrenia revisited . Psychoneuroendocrinology 1979;;4:37-46.
13 +
Stevens JR, Wilson K, Foote W:  GABA blockade, dopamine and schizophrenia: Experimental studies in the cat . Psychopharmacologia 1974;;39:105-119.
14 +
Roberts E:  An hypothesis suggesting that there is a deficit in the GABA system in schizophrenia . Neurosci Res Program Bull 1972;;10:468-483.
15 +
Roberts E:  Disinhibition as an organizing principle in the nervous system—the role of the GABA system: Application to neurologic and psychiatric disorders , in Roberts E, Chase TN, Tower DB (eds): GABA in Nervous System Function . New York, Raven Press, 1976;, pp 515-539.
16 +
Van Kammen DP:  γ-Aminobutyric acid (GABA) and the dopamine hypothesis of schizophrenia . Am J Psychiatry 1977;;134:138-143.
17 +
Glaeser BS, Hare TA:  Measurement of GABA in human cerebrospinal fluid . Biochem Med 1975;;12:274-282.
18 +
Langer DH, Brown GLV, Bunney WE Jr, et al:  Gamma-aminobutyric acid in CSF in schizophrenia . N Engl J Med 1975;;293:201.
19 +
Huizinga JA, Teelken AW, Muskiet FAJ, et al:  Identification of GABA in human CSF bv gas liquid chromatography and mass spectrometry . N Engl J Med 1977;;296:692.
20 +
Enna SJ, Wood JH, Snyder SH:  Gamma-aminobutyric acid (GABA) in human cerebrospinal fluid: Radioreceptor assay . J Neurochem 1977;;28:1121-1124.
21 +
Enna SJ, Ziegler MG, Lake CR, et al:  CSF GABA: Correlation with CSF and blood constituents and alteration in neurological disorders , in Wood JH (ed): Neurobiology of Cerebrospinal Fluid . New York, Plenum Press, 1980;, vol 1, pp 189-196.
22 +
Faull KF, DoAmaral JR, Berger PA, et al:  Mass spectrometric identification and selected ion monitoring quantitation of gamma-aminobutyric acid (GABA) in human lumbar cerebrospinal fluid . J Neurochem 1978;;31:1119-1122.
23 +
Neethling AC, McCarthy B, Taljaard JJF:  Gamma-aminobutyric acid in CSF . Lancet 1980;;1:211.
24 +
Manyam NVB, Katz L, Hare T, et al:  Levels of gamma-aminobutyric acid in cerebrospinal fluid in various neurologic disorders . Arch Neurol 1980;;37:352-355.
25 +
Wood JH, Hare TA, Enna SJ, et al:  Sites of origin and rostrocaudal concentration gradients of GABA in cerebrospinal fluid . Brain Res 1980;;5:111-114.
26 +
Hare TA, Wood JH, Manyam NVB:  Selection of control populations for clinical cerebrospinal fluid GABA investigations based on comparison with normal volunteers . Brain Res 1980;;5:721-724.
27 +
Van Kammen DP, Sternberg DE:  CSF studies in schizophrenia , in Wood JH (ed): The Neurobiology of Spinal Fluid . New York, Plenum Press, 1980;, vol 1, pp 719-749.
28 +
Cross AJ, Crow TJ, Owen F:  Gamma-aminobutyric acid in the brain in schizophrenia . Lancet 1979;;1:560-561.
29 +
Perry TL, Buchanan J, Kish SJ, et al:  γ-Aminobutyric acid deficiency in brain of schizophrenic patients . Lancet . 1979;;1:237.
30 +
Iversen LL, Bird E, Spokes E, et al:  Agonist specificity of GABA binding sites in human brain and GABA in Huntington 's disease and schizophrenia , in Krogsgaard-Larsen P, Scheel-Krüger J, Kofod H (eds): GABA-Neuro-transmitters: Pharmacochemical, Biochemical and Pharmacological Aspects . New York, Academic Press Inc, 1979;, pp 177-190.
31 +
Bennett JP, Enna SJ, Bylund DB, et al:  Neurotransmitter receptors in frontal cortex of schizophrenics . Arch Gen Psychiatry 1979;;36:927-934.
32 +
White HL, Davidson JRT, Miller RD, et al:  Platelet gamma-aminobutyrate-α-ketoglutarate transaminase (GABA-T) in schizophrenia . Am J Psychiatry 1980;;137:733-734.
33 +
Zander KJ, Fischer B, Zimmer R, et al:  Long-term neuroleptic treatment of schizophrenic patients: Clinical and biochemical effects of withdrawal . Psychopharmacology 1981;;73:43-47.
34 +
McCarthy BW, Gomes UR, Neethling AC, et al:  Gamma-aminobutyric acid concentration in cerebrospinal fluid in schizophrenia . J Neurochem 1981;;36:1406-1408.
35 +
Van Kammen DP, Sternberg DE, Hare TA, et al:  Spinal fluid GABA levels in schizophrenia , in Angrist B, Burrows GD, Lader M, et al (eds): Biochemistry of the Human Cerebrospinal Fluid, vol 31, in Advances in the Bio-Sciences . New York, Pergamon Press, 1981;, pp 315-321.
36 +
Lichtshtein D, Dobkin J, Ebstein RP, et al:  Gamma-aminobutyric acid (GABA) in the CSF of schizophrenic patients before and after neuroleptic treatment . Br J Psychiatry 1978;;132:145-148.
37 +
Gold BI, Bowers MB, Roth RH, et al:  GABA levels in CSF of patients with psychiatric disorders . Am J Psychiatry 1980;;137:362-364.
38 +
Bowers MB, Gold BI, Roth RH:  CSF GABA in psychotic disorders . Psychopharmacology 1980;;70:279-282.
39 +
Gerner RH, Hare TA:  CSF GABA in normals, depression, schizophrenia, mania and anorexia nervosa . Am J Psychiatry 1981;;138:1098-1101.
40 +
Cattabeni F, Maggi A, Monduzzi M:  GABA: Circadian fluctuations in rat hypothalamus . J Neurochem 1978;;31:565-567.
41 +
Wood JH:  Neurochemical analysis of cerebrospinal fluid . Neurology 1980;;30:645-651.
42 +
Costa E, Cheney DL, Mao CC, et al:  Action of antischizophrenic drugs on the metabolism of gamma-aminobutyric acid and acetylcholine in globus pallidus, striatum and n accumbens . Fed Proc 1978;;37:2408-2414.
43 +
Fjalland B:  Inhibition by neuroleptics of uptake of 3H-GABA into rat brain synaptosomes . Acta Pharmacol Toxicol 1978;;42:73-76.
44 +
Lloyd KG, Hornykiewicz 0:  Effect of chronic neuroleptic of L-DOPA administration on GABA levels in the rat substantia nigra . Life Sci 1977;;21:1489-1496.
45 +
Perry TL, Hansen S, Kish SJ:  Effects of chronic administration of antipsychotic drugs on GABA and other amino acids in the mesolimbic area of rat brain . Life Sci 1979;;24:283-288.
46 +
Pinder RM, Brogden RM, Sawyer PR, et al:  Pimozide: A review of its pharmacological properties and therapeutic uses in psychiatry . Drugs 1976;;12:1-40.
47 +
Spitzer RL, Endicott J, Robins E: Research Diagnostic Criteria for a Selected Group of Functional Disorders . New York, Biometrics Research Division, New York State Psychiatric Institute, 1978;.
48 +
Carpenter WT, Strauss JS, Bartko JJ:  Flexible system for the diagnosis of schizophrenia: Report from the WHO International Pilot Study of Schizophrenia . Science 1973;;182:1275-1278.
49 +
Hare TH, Wood JH, Ballenger JC, et al:  Gamma-aminobutyric acid in human cerebrospinal fluid: Normal values . Lancet 1979;;2:534-535.
50 +
Phillips L:  Case history data and prognosis in schizophrenia . J Nerv Ment Dis 1953;;117:515-525.
51 +
Gochman N, Schmitz JM:  Application of a new peroxidase indicator reaction to the specific, automated determination of glucose with glucose oxidase . Clin Chem 1972;;18:943-950.
52 +
Bunney WE, Hamburg DA:  Methods for reliable longitudinal observation of behavior . Arch Gen Psychiatry 1963;;9:280-294.
53 +
Hare TA, Manyam NVB:  Rapid and sensitive ion exchange/fluorometric method for measuring GABA on physiological fluids . Anal Biochem 1980;;101:349-355.
54 +
Bowers MB Jr, Heninger GR, Sternberg D:  Clinical processes and central dopaminergic activity in psychotic disorders . Commun Psychopharmacol 1980;;4:177-188.
55 +
McKhann GM, Albers RW, Sokoloff L, et al:  The quantitative significance of the gamma-aminobutyric acid pathway in cerebral oxidative metabolism , in Roberts E, Baster CF, van Harreveld A, et al (eds): Inhibition in the Nervous System and Gamma-Aminobutyric Acid . New York, Pergamon Press, 1960;, pp 169-181.
56 +
Gibson GE, Peterson C, Sansone J: Hypoxia decreases the metabolism of the glucose-derived neurotransmitters. Read before the tenth annual meeting of the Society for Neurosciences, Cincinnati, Nov 9, 1980.
57 +
Grace AA, Bunney BS:  Paradoxical GABA excitation of nigral dopaminergic cells: Indirect mediation through reticulata inhibitory neurons . Eur J Pharmacol 1979;;59:211-218.
58 +
Waszczak BL, Walters JR:  Intravenous GABA agonist administration stimulates firing of A10 dopaminergic neurons . Eur J Pharmacol 1980;;66:141-144.
59 +
Arnt J, Scheel-Krüger J:  GABAergic and glycinergic mechanisms within the substantia nigra: Pharmacological specificity of dopamineindependent contralateral turning behavior and interactions with other neurotransmitters . Psychopharmacology 1979;;62:267-277.
60 +
Van der Heyden JAM, Venema K, Korf J:  Biphasic and opposite effects of dopamine and apomorphine on endogenous GABA release in the rat substantia nigra . J Neurochem 1980;;34:119-125.
61 +
Crow TJ:  Molecular pathology of schizophrenia: More than one disease process? Br Med J 1980;;280:66-68.
62 +
Simeon J, Fink M, Itil TM, et al:  d-Cycloserine therapy on psychosis by symptom provocation . Comp Psychiatry 1970;;11:80-88.
63 +
Tamminga CA, Crayton JW, Chase TN:  Muscimol: GABA agonist therapy in schizophrenia . Am J Psychiatry 1978;;135:746-747.
64 +
Schulz SC, van Kammen DP, Buchsbaum MS, et al:  Gamma-hydroxybutyrate treatment of schizophrenia: A pilot study . Pharmacopsychiatry 1981;;14:129-134.
65 +
Simpson GM, Branchex MM, Shrivastava RK:  Baclofen in schizophrenia . Lancet 1975;;1:966-967.
66 +
Bartholini G, Cuche H, Zarifian E, et al:  Involvement of cholinergic and GABAergic systems in schizophrenia , in Obiol J, Ballus C, Gonzalesmonclus E, et al (eds): Biological Psychiatry Today . Amsterdam, Elsevier North Holland Biomédical Press, 1979;, pp 439-444.
67 +
Bartholini G, Scatton B, Zivkovic B, et al:  On the mode of action of SL 76002, a new GABA receptor agonist , in Krogsgaard-Larsen P, Scheel Krüger J, Kofod H (eds): GABA-Neurotransmitters , Alfred Benson Symposium Series, vol 12. New York, Academic Press Inc, 1979;, pp 326-339.
68 +
Linnoila M, Viukari M, Hietala O:  Effect of sodium valproate on tardive dyskinesia . Br J Psychiatry 1976;;129:114-119.
69 +
Casey DE, Gerlach J, Magelund G, et al:  Gamma-acetylenic GABA in tardive dyskinesia . Arch Gen Psychiatry 1980;;37:1376-1379.
70 +
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To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
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Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
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Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
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AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
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