Skip to content
2000
image of Can Sodium Oxybate Mitigate the Symptoms of Schizophrenia?

Abstract

Schizophrenia remains a therapeutic challenge. For much of its long history, the physiological basis of its symptoms and clinical presentation remained elusive. However, in recent decades, consistent anatomical and metabolic changes have been documented that can also serve as therapeutic targets. An insult to the developing nervous system in the prenatal or neonatal period appears to set the schizophrenic syndrome in motion by preventing the development of the normal circuit balance between inhibitory and excitatory neurons. In time, a reduction in the volume of frontal and temporal grey matter and a decrease in the density of dendritic spines on pyramidal neurons becomes apparent. These anatomical findings are accompanied by a reduced capacity to synthesize GABA, an increased capacity to synthesize and release dopamine, and an increased level of blood cortisol. Treatment with sodium oxybate (SO) (gammahydroxybutyrate) may make it possible to reverse these pathological features of the schizophrenic syndrome, given SO’s potential to increase neuronal levels of GABA, inhibit dopamine release and reduce blood cortisol levels. SO can also serve as a source of energy to promote the growth of the dendritic arbor on excitatory pyramidal neurons and as an antioxidant to enhance the activity of GABAergic inhibitory neurons. In this way, SO may restore the balance between the excitatory pyramidal neurons and the inhibitory GABAergic neurons in schizophrenia. In a short clinical trial, the use of SO to improve the sleep of patients with chronic schizophrenia led to a significant clinical improvement.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cn/10.2174/011570159X377481250526110256
2025-06-04
2025-10-30

  • From This Site

    /content/journals/cn/10.2174/011570159X377481250526110256
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Lehmann H.E. Ban T.A. The history of the psychopharmacology of schizophrenia. Can. J. Psychiatry 1997 42 2 152 162 10.1177/070674379704200205 9067064
    [Google Scholar]
  2. Harrison P.J. The neuropathology of schizophrenia. Brain 1999 122 4 593 624 10.1093/brain/122.4.593 10219775
    [Google Scholar]
  3. Benes F. Emerging principles of altered neural circuitry in schizophrenia. Brain Res. Brain Res. Rev. 2000 31 2-3 251 269 10.1016/S0165‑0173(99)00041‑7 10719152
    [Google Scholar]
  4. Lewis D.A. Hashimoto T. Volk D.W. Cortical inhibitory neurons and schizophrenia. Nat. Rev. Neurosci. 2005 6 4 312 324 10.1038/nrn1648 15803162
    [Google Scholar]
  5. Harrison P.J. Postmortem studies in schizophrenia. Dialogues Clin. Neurosci. 2000 2 4 349 357 10.31887/DCNS.2000.2.4/pharrison 22033474
    [Google Scholar]
  6. Holtzman C.W. Trotman H.D. Goulding S.M. Ryan A.T. MacDonald A.N. Shapiro D.I. Brasfield J.L. Walker E.F. Stress and neurodevelopmental processes in the emergence of psychosis. Neuroscience 2013 249 172 191 10.1016/j.neuroscience.2012.12.017 23298853
    [Google Scholar]
  7. Takahashi T. Suzuki M. Brain morphologic changes in early stages of psychosis: Implications for clinical application and early intervention. Psychiatry Clin. Neurosci. 2018 72 8 556 571 10.1111/pcn.12670 29717522
    [Google Scholar]
  8. Takahashi T. Higuchi Y. Komori Y. Nishiyama S. Takayanagi Y. Sasabayashi D. Kido M. Furuichi A. Nishikawa Y. Nakamura M. Noguchi K. Suzuki M. Pituitary volume and socio-cognitive functions in individuals at risk of psychosis and patients with schizophrenia. Front. Psychiatry 2018 9 574 10.3389/fpsyt.2018.00574 30473669
    [Google Scholar]
  9. Takahashi T. Suzuki M. Velakoulis D. Lorenzetti V. Soulsby B. Zhou S.Y. Nakamura K. Seto H. Kurachi M. Pantelis C. Increased pituitary volume in schizophrenia spectrum disorders. Schizophr. Res. 2009 108 1-3 114 121 10.1016/j.schres.2008.12.016 19162445
    [Google Scholar]
  10. Thalhammer M. Schulz J. Scheulen F. Oubaggi M.E.M. Kirschner M. Kaiser S. Schmidt A. Borgwardt S. Avram M. Brandl F. Sorg C. Sorg C. Distinct volume alterations of thalamic nuclei across the schizophrenia spectrum. Schizophr. Bull. 2024 50 5 1208 1222 10.1093/schbul/sbae037 38577901
    [Google Scholar]
  11. Fusar-Poli P. Borgwardt S. Crescini A. Deste G. Kempton M.J. Lawrie S. Mc Guire P. Sacchetti E. Neuroanatomy of vulnerability to psychosis: A voxel-based meta-analysis. Neurosci. Biobehav. Rev. 2011 35 5 1175 1185 10.1016/j.neubiorev.2010.12.005 21168439
    [Google Scholar]
  12. Hulshoff Pol H.E. Kahn R.S. What happens after the first episode? A review of progressive brain changes in chronically ill patients with schizophrenia. Schizophr. Bull. 2007 34 2 354 366 10.1093/schbul/sbm168 18283048
    [Google Scholar]
  13. Borgwardt S.J. Picchioni M.M. Ettinger U. Toulopoulou T. Murray R. McGuire P.K. Regional gray matter volume in monozygotic twins concordant and discordant for schizophrenia. Biol. Psychiatry 2010 67 10 956 964 10.1016/j.biopsych.2009.10.026 20006324
    [Google Scholar]
  14. Brosch K. Stein F. Schmitt S. Pfarr J.K. Ringwald K.G. Thomas-Odenthal F. Meller T. Steinsträter O. Waltemate L. Lemke H. Meinert S. Winter A. Breuer F. Thiel K. Grotegerd D. Hahn T. Jansen A. Dannlowski U. Krug A. Nenadić I. Kircher T. Reduced hippocampal gray matter volume is a common feature of patients with major depression, bipolar disorder, and schizophrenia spectrum disorders. Mol. Psychiatry 2022 27 10 4234 4243 10.1038/s41380‑022‑01687‑4 35840798
    [Google Scholar]
  15. Kim E.J. Pellman B. Kim J.J. Stress effects on the hippocampus: A critical review. Learn. Mem. 2015 22 9 411 416 10.1101/lm.037291.114 26286651
    [Google Scholar]
  16. Brown E.S. Jeon-Slaughter H. Lu H. Jamadar R. Issac S. Shad M. Denniston D. Tamminga C. Nakamura A. Thomas B.P. Hippocampal volume in healthy controls given 3-day stress doses of hydrocortisone. Neuropsychopharmacology 2015 40 5 1216 1221 10.1038/npp.2014.307 25409592
    [Google Scholar]
  17. Ringwald K.G. Pfarr J.K. Stein F. Brosch K. Meller T. Thomas-Odenthal F. Meinert S. Waltemate L. Breuer F. Winter A. Lemke H. Grotegerd D. Thiel K. Bauer J. Hahn T. Jansen A. Dannlowski U. Krug A. Nenadić I. Kircher T. Association between stressful life events and grey matter volume in the medial prefrontal cortex: A 2‐year longitudinal study. Hum. Brain Mapp. 2022 43 11 3577 3584 10.1002/hbm.25869 35411559
    [Google Scholar]
  18. Cullen A.E. Fisher H.L. Gullet N. Fraser E.R. Roberts R.E. Zahid U. To M. Yap N.H. Zunszain P.A. Pariante C.M. Wood S.J. McGuire P. Murray R.M. Mondelli V. Laurens K.R. Cortisol levels in childhood associated with emergence of attenuated psychotic symptoms in early adulthood. Biol. Psychiatry 2022 91 2 226 235 10.1016/j.biopsych.2021.08.009 34715990
    [Google Scholar]
  19. Pruessner M. Cullen A.E. Aas M. Walker E.F. The neural diathesis-stress model of schizophrenia revisited: An update on recent findings considering illness stage and neurobiological and methodological complexities. Neurosci. Biobehav. Rev. 2017 73 191 218 10.1016/j.neubiorev.2016.12.013 27993603
    [Google Scholar]
  20. Aymerich C. Pedruzo B. Pacho M. Laborda M. Herrero J. Pillinger T. McCutcheon R.A. Alonso-Alconada D. Bordenave M. Martínez-Querol M. Arnaiz A. Labad J. Fusar-Poli P. González-Torres M.Á. Catalan A. Prolactin and morning cortisol concentrations in antipsychotic naïve first episode psychosis: A systematic review and meta-analysis. Psychoneuroendocrinology 2023 150 106049 10.1016/j.psyneuen.2023.106049
    [Google Scholar]
  21. Misiak B. Pruessner M. Samochowiec J. Wiśniewski M. Reginia A. Stańczykiewicz B. A meta-analysis of blood and salivary cortisol levels in first-episode psychosis and high-risk individuals. Front. Neuroendocrinol. 2021 62 100930 10.1016/j.yfrne.2021.100930 34171354
    [Google Scholar]
  22. Hubbard D.B. Miller B.J. Meta-analysis of blood cortisol levels in individuals with first-episode psychosis. Psychoneuroendocrinology 2019 104 269 275 10.1016/j.psyneuen.2019.03.014 30909008
    [Google Scholar]
  23. Benes F.M. Lim B. Matzilevich D. Walsh J.P. Subburaju S. Minns M. Regulation of the GABA cell phenotype in hippocampus of schizophrenics and bipolars. Proc. Natl. Acad. Sci. USA 2007 104 24 10164 10169 10.1073/pnas.0703806104 17553960
    [Google Scholar]
  24. Curley A.A. Eggan S.M. Lazarus M.S. Huang Z.J. Volk D.W. Lewis D.A. Role of glutamic acid decarboxylase 67 in regulating cortical parvalbumin and GABA membrane transporter 1 expression: Implications for schizophrenia. Neurobiol. Dis. 2013 50 179 186 10.1016/j.nbd.2012.10.018 23103418
    [Google Scholar]
  25. Thompson M. Weickert C.S. Wyatt E. Webster M.J. Decreased glutamic acid decarboxylase67 mRNA expression in multiple brain areas of patients with schizophrenia and mood disorders. J. Psychiatr. Res. 2009 43 11 970 977 10.1016/j.jpsychires.2009.02.005 19321177
    [Google Scholar]
  26. Benes F.M. Amygdalocortical circuitry in schizophrenia: From circuits to molecules. Neuropsychopharmacology 2010 35 1 239 257 10.1038/npp.2009.116 19727065
    [Google Scholar]
  27. Lau C.G. Murthy V.N. Activity-dependent regulation of inhibition via GAD67. J. Neurosci. 2012 32 25 8521 8531 10.1523/JNEUROSCI.1245‑12.2012 22723692
    [Google Scholar]
  28. Martin DL Rimvall K Regulation of γ‐aminobutyric acid synthesis in the brain. J. Neurochem. 1993 60 2 395 407 10.1111/j.1471‑4159.1993.tb03165.x
    [Google Scholar]
  29. Andersen J.V. Schousboe A. Wellendorph P. Astrocytes regulate inhibitory neurotransmission through GABA uptake, metabolism, and recycling. Essays Biochem. 2023 67 1 77 91 10.1042/EBC20220208 36806927
    [Google Scholar]
  30. Andersen J.V. Schousboe A. Glial Glutamine Homeostasis in Health and Disease. Neurochem. Res. 2023 48 4 1100 1128 10.1007/s11064‑022‑03771‑1 36322369
    [Google Scholar]
  31. Dienel S.J. Lewis D.A. Alterations in cortical interneurons and cognitive function in schizophrenia. Neurobiol. Dis. 2019 131 104208 10.1016/j.nbd.2018.06.020 29936230
    [Google Scholar]
  32. Dienel S.J. Fish K.N. Lewis D.A. The nature of prefrontal cortical gaba neuron alterations in schizophrenia: Markedly lower somatostatin and parvalbumin gene expression without missing neurons. Am. J. Psychiatry 2023 180 7 495 507 10.1176/appi.ajp.20220676 37073488
    [Google Scholar]
  33. Georgiev D. Yoshihara T. Kawabata R. Matsubara T. Tsubomoto M. Minabe Y. Lewis D.A. Hashimoto T. Cortical gene expression after a conditional knockout of 67 kDa glutamic acid decarboxylase in parvalbumin neurons. Schizophr. Bull. 2016 42 4 992 1002 10.1093/schbul/sbw022 26980143
    [Google Scholar]
  34. Karolewicz B. Maciag D. O’Dwyer G. Stockmeier C.A. Feyissa A.M. Rajkowska G. Reduced level of glutamic acid decarboxylase-67 kDa in the prefrontal cortex in major depression. Int. J. Neuropsychopharmacol. 2010 13 4 411 420 10.1017/S1461145709990587 20236554
    [Google Scholar]
  35. Dienel S.J. Schoonover K.E. Lewis D.A. Cognitive dysfunction and prefrontal cortical circuit alterations in schizophrenia: Developmental trajectories. Biol. Psychiatry 2022 92 6 450 459 10.1016/j.biopsych.2022.03.002 35568522
    [Google Scholar]
  36. Schoonover K.E. Dienel S.J. Lewis D.A. Prefrontal cortical alterations of glutamate and GABA neurotransmission in schizophrenia: Insights for rational biomarker development. Biomark. Neuropsychiatry 2020 3 100015 10.1016/j.bionps.2020.100015 32656540
    [Google Scholar]
  37. Glausier J.R. Enwright J.F. Lewis D.A. Ph D. Lewis D.A. Diagnosis- and cell type-specific mitochondrial functional pathway signatures in schizophrenia and bipolar disorder. Am. J. Psychiatry 2020 177 12 1140 1150 10.1176/appi.ajp.2020.19111210 33115248
    [Google Scholar]
  38. Schoonover K.E. Miller N.E. Fish K.N. Lewis D.A. Scaling of smaller pyramidal neuron size and lower energy production in schizophrenia. Neurobiol. Dis. 2024 191 106394 10.1016/j.nbd.2023.106394 38176569
    [Google Scholar]
  39. Chung D.W. Fish K.N. Lewis D.A. Lewis D.A. Pathological basis for deficient excitatory drive to cortical parvalbumin interneurons in schizophrenia. Am. J. Psychiatry 2016 173 11 1131 1139 10.1176/appi.ajp.2016.16010025 27444795
    [Google Scholar]
  40. Mallya A.P. Deutch A.Y. (Micro)Glia as effectors of cortical volume loss in schizophrenia. Schizophr. Bull. 2018 44 5 948 957 10.1093/schbul/sby088 30124942
    [Google Scholar]
  41. MacDonald M.L. Alhassan J. Newman J.T. Richard M. Gu H. Kelly R.M. Sampson A.R. Fish K.N. Penzes P. Wills Z.P. Lewis D.A. Sweet R.A. Selective loss of smaller spines in schizophrenia. Am. J. Psychiatry 2017 174 6 586 594 10.1176/appi.ajp.2017.16070814 28359200
    [Google Scholar]
  42. Feinberg I. Schizophrenia: Caused by a fault in programmed synaptic elimination during adolescence? J. Psychiatr. Res. 1982 17 4 319 334 10.1016/0022‑3956(82)90038‑3 7187776
    [Google Scholar]
  43. Bollinger J.L. Wohleb E.S. The formative role of microglia in stress-induced synaptic deficits and associated behavioral consequences. Neurosci. Lett. 2019 711 134369 10.1016/j.neulet.2019.134369 31422099
    [Google Scholar]
  44. Howes O.D. Onwordi E.C. The synaptic hypothesis of schizophrenia version III: A master mechanism. Mol. Psychiatry 2023 28 5 1843 1856 10.1038/s41380‑023‑02043‑w 37041418
    [Google Scholar]
  45. Wang J. Chen H.S. Li H.H. Wang H.J. Zou R.S. Lu X.J. Wang J. Nie B.B. Wu J.F. Li S. Shan B.C. Wu P.F. Long L.H. Hu Z.L. Chen J.G. Wang F. Microglia-dependent excessive synaptic pruning leads to cortical underconnectivity and behavioral abnormality following chronic social defeat stress in mice. Brain Behav. Immun. 2023 109 23 36 10.1016/j.bbi.2022.12.019 36581303
    [Google Scholar]
  46. Jenkins A.K. Lewis D.A. Volk D.W. Altered expression of microglial markers of phagocytosis in schizophrenia. Schizophr. Res. 2023 251 22 29 10.1016/j.schres.2022.12.005 36527956
    [Google Scholar]
  47. Glausier J.R. Lewis D.A. Dendritic spine pathology in schizophrenia. Neuroscience 2013 251 90 107 10.1016/j.neuroscience.2012.04.044 22546337
    [Google Scholar]
  48. Sanacora G. Yan Z. Popoli M. The stressed synapse 2.0: Pathophysiological mechanisms in stress-related neuropsychiatric disorders. Nat. Rev. Neurosci. 2022 23 2 86 103 10.1038/s41583‑021‑00540‑x 34893785
    [Google Scholar]
  49. Yuen E.Y. Wei J. Liu W. Zhong P. Li X. Yan Z. Repeated stress causes cognitive impairment by suppressing glutamate receptor expression and function in prefrontal cortex. Neuron 2012 73 5 962 977 10.1016/j.neuron.2011.12.033 22405206
    [Google Scholar]
  50. Cooper M.A. Koleske A.J. Manuscript A. Ablation of ErbB4 from excitatory neurons leads to reduced dendritic spine density in mouse prefrontal cortex. J. Comp. Neurol. 2014 522 14 3351 3362 10.1002/cne.23615 24752666
    [Google Scholar]
  51. Popov V.I. Medvedev N.I. Patrushev I.V. Ignat’ev D.A. Morenkov E.D. Stewart M.G. Reversible reduction in dendritic spines in CA1 of rat and ground squirrel subjected to hypothermia–normothermia in vivo: A three-dimensional electron microscope study. Neuroscience 2007 149 3 549 560 10.1016/j.neuroscience.2007.07.059 17919827
    [Google Scholar]
  52. Roberts R.C. Postmortem studies on mitochondria in schizophrenia. Schizophr. Res. 2017 187 17 25 10.1016/j.schres.2017.01.056 28189530
    [Google Scholar]
  53. Townsend L. Pillinger T. Selvaggi P. Veronese M. Turkheimer F. Howes O. Brain glucose metabolism in schizophrenia: A systematic review and meta-analysis of 18 FDG-PET studies in schizophrenia. Psychol. Med. 2023 53 11 4880 4897 10.1017/S003329172200174X 35730361
    [Google Scholar]
  54. Hyder F. Patel A.B. Gjedde A. Rothman D.L. Behar K.L. Shulman R.G. Neuronal-glial glucose oxidation and glutamatergic-GABAergic function. J. Cereb. Blood Flow Metab. 2006 26 7 865 877 10.1038/sj.jcbfm.9600263 16407855
    [Google Scholar]
  55. Rothman D.L. Behar K.L. Dienel G.A. Mechanistic stoichiometric relationship between the rates of neurotransmission and neuronal glucose oxidation: Reevaluation of and alternatives to the pseudo- malate- aspartate shuttle model. J. Neurochem. 2022 00 1 37 36089566
    [Google Scholar]
  56. Hertz L. Chen Y. Integration between glycolysis and glutamate-glutamine cycle flux may explain preferential glycolytic increase during brain activation, requiring glutamate. Front. Integr. Nuerosci. 2017 11 18 10.3389/fnint.2017.00018 28890689
    [Google Scholar]
  57. Mishra P.K. Adusumilli M. Deolal P. Mason G.F. Kumar A. Patel A.B. Impaired neuronal and astroglial metabolic activity in chronic unpredictable mild stress model of depression: Reversal of behavioral and metabolic deficit with lanicemine. Neurochem. Int. 2020 137 104750 10.1016/j.neuint.2020.104750 32360130
    [Google Scholar]
  58. Orhan F. Fatouros-Bergman H. Goiny M. Malmqvist A. Piehl F. Cervenka S. Collste K. Victorsson P. Sellgren C.M. Flyckt L. Erhardt S. Engberg G. CSF GABA is reduced in first-episode psychosis and associates to symptom severity. Mol. Psychiatry 2018 23 5 1244 1250 10.1038/mp.2017.25 28289277
    [Google Scholar]
  59. Frankle W.G. Cho R.Y. Prasad K.M. Mason N.S. Paris J. Himes M.L. Walker C. Lewis D.A. Narendran R. In vivo measurement of GABA transmission in healthy subjects and schizophrenia patients. Am. J. Psychiatry 2015 172 11 1148 1159 10.1176/appi.ajp.2015.14081031 26133962
    [Google Scholar]
  60. Godlewska B.R. Minichino A. Emir U. Angelescu I. Lennox B. Micunovic M. Howes O. Cowen P.J. Brain glutamate concentration in men with early psychosis: a magnetic resonance spectroscopy case–control study at 7 T. Transl. Psychiatry 2021 11 1 367 10.1038/s41398‑021‑01477‑6 34226485
    [Google Scholar]
  61. Lavigne K.M. Kanagasabai K. Palaniyappan L. Ultra-high field neuroimaging in psychosis: A narrative review. Front. Psychiatry 2022 13 994372 994372 10.3389/fpsyt.2022.994372 36506432
    [Google Scholar]
  62. Marsman A. Mandl R.C.W. Klomp D.W.J. Bohlken M.M. Boer V.O. Andreychenko A. Cahn W. Kahn R.S. Luijten P.R. Hulshoff Pol H.E. GABA and glutamate in schizophrenia: A 7 T 1H-MRS study. Neuroimage Clin. 2014 6 398 407 10.1016/j.nicl.2014.10.005 25379453
    [Google Scholar]
  63. Reid M.S. Tafti M. Nishino S. Sampathkumaran R. Siegel J.M. Mignot E. Local administration of dopaminergic drugs into the ventral tegmental area modulates cataplexy in the narcoleptic canine. Brain Res. 1996 733 1 83 100 10.1016/0006‑8993(96)00541‑0 8891251
    [Google Scholar]
  64. Thakkar K.N. Rösler L. Wijnen J.P. Boer V.O. Klomp D.W.J. Cahn W. Kahn R.S. Neggers S.F.W. 7T proton magnetic resonance spectroscopy of gamma-aminobutyric acid, glutamate, and glutamine reveals altered concentrations in patients with schizophrenia and healthy siblings. Biol. Psychiatry 2017 81 6 525 535 10.1016/j.biopsych.2016.04.007 27316853
    [Google Scholar]
  65. Wang A.M. Pradhan S. Coughlin J.M. Trivedi A. DuBois S.L. Crawford J.L. Sedlak T.W. Nucifora F.C. Nestadt G. Nucifora L.G. Schretlen D.J. Sawa A. Barker P.B. Assessing brain metabolism With 7-T proton magnetic resonance spectroscopy in patients with first-episode psychosis. JAMA Psychiatry 2019 76 3 314 323 10.1001/jamapsychiatry.2018.3637 30624573
    [Google Scholar]
  66. Wijtenburg S.A. Wang M. Korenic S.A. Chen S. Barker P.B. Rowland L.M. Metabolite alterations in adults with schizophrenia, first degree relatives, and healthy controls: A multi-region 7T MRS study. Front. Psychiatry 2021 12 656459 10.3389/fpsyt.2021.656459 34093272
    [Google Scholar]
  67. Butterfield D.A. Halliwell B. Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease. Nat. Rev. Neurosci. 2019 20 3 148 160 10.1038/s41583‑019‑0132‑6 30737462
    [Google Scholar]
  68. Prabakaran S. Swatton J.E. Ryan M.M. Huffaker S.J. Huang J.T-J. Griffin J.L. Wayland M. Freeman T. Dudbridge F. Lilley K.S. Karp N.A. Hester S. Tkachev D. Mimmack M.L. Yolken R.H. Webster M.J. Torrey E.F. Bahn S. Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol. Psychiatry 2004 9 7 684 697, 643 10.1038/sj.mp.4001511 15098003
    [Google Scholar]
  69. Martins-de-Souza D. Maccarrone G. Wobrock T. Zerr I. Gormanns P. Reckow S. Falkai P. Schmitt A. Turck C.W. Proteome analysis of the thalamus and cerebrospinal fluid reveals glycolysis dysfunction and potential biomarkers candidates for schizophrenia. J. Psychiatr. Res. 2010 44 16 1176 1189 10.1016/j.jpsychires.2010.04.014 20471030
    [Google Scholar]
  70. Sydnor V.J. Roalf D.R. A meta-analysis of ultra-high field glutamate, glutamine, GABA and glutathione 1HMRS in psychosis: Implications for studies of psychosis risk. Schizophr. Res. 2020 226 61 69 10.1016/j.schres.2020.06.028 32723493
    [Google Scholar]
  71. Yang K. Longo L. Narita Z. Cascella N. Nucifora F.C. Coughlin J.M. Nestadt G. Sedlak T.W. Mihaljevic M. Wang M. Kenkare A. Nagpal A. Sethi M. Kelly A. Di Carlo P. Kamath V. Faria A. Barker P. Sawa A. A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance. Mol. Psychiatry 2022 27 2 1184 1191 10.1038/s41380‑021‑01331‑7 34642460
    [Google Scholar]
  72. Dwir D. Khadimallah I. Xin L. Rahman M. Du F. Öngür D. Do K.Q. Redox and immune signaling in schizophrenia: new therapeutic potential. Int. J. Neuropsychopharmacol. 2023 26 5 309 321 10.1093/ijnp/pyad012 36975001
    [Google Scholar]
  73. Zafir A. Banu N. Modulation of in vivo oxidative status by exogenous corticosterone and restraint stress in rats. Stress 2009 12 2 167 177 10.1080/10253890802234168 18850490
    [Google Scholar]
  74. Cuenod M. Steullet P. Cabungcal J.H. Dwir D. Khadimallah I. Klauser P. Conus P. Do K.Q. Caught in vicious circles: A perspective on dynamic feed-forward loops driving oxidative stress in schizophrenia. Mol. Psychiatry 2022 27 4 1886 1897 10.1038/s41380‑021‑01374‑w 34759358
    [Google Scholar]
  75. Berretta S. Pantazopoulos H. Markota M. Brown C. Batzianouli E.T. Losing the sugar coating: Potential impact of perineuronal net abnormalities on interneurons in schizophrenia. Schizophr. Res. 2015 167 1-3 18 27 10.1016/j.schres.2014.12.040 25601362
    [Google Scholar]
  76. Enwright J.F. Sanapala S. Foglio A. Berry R. Fish K.N. Lewis D.A. Reduced labeling of parvalbumin neurons and perineuronal nets in the dorsolateral prefrontal cortex of subjects with schizophrenia. Neuropsychopharmacology 2016 41 9 2206 2214 10.1038/npp.2016.24 26868058
    [Google Scholar]
  77. Cabungcal J.H. Steullet P. Kraftsik R. Cuenod M. Do K.Q. Early-life insults impair parvalbumin interneurons via oxidative stress: Reversal by N-acetylcysteine. Biol. Psychiatry 2013 73 6 574 582 10.1016/j.biopsych.2012.09.020 23140664
    [Google Scholar]
  78. Beeraka N.M. Avila-Rodriguez M.F. Aliev G. Recent reports on redox stress-induced mitochondrial DNA variations, neuroglial interactions, and NMDA receptor system in pathophysiology of schizophrenia. Mol. Neurobiol. 2022 59 4 2472 2496 10.1007/s12035‑021‑02703‑4 35083660
    [Google Scholar]
  79. Baxter P.S. Bell K.F.S. Hasel P. Kaindl A.M. Fricker M. Thomson D. Cregan S.P. Gillingwater T.H. Hardingham G.E. Synaptic NMDA receptor activity is coupled to the transcriptional control of the glutathione system. Nat. Commun. 2015 6 1 6761 10.1038/ncomms7761 25854456
    [Google Scholar]
  80. Papadia S. Soriano .X. Léveillé F. Martel M-A. Dakin K.A. Hansen H.H. Kaindl A. Sifringer M. Fowler J. Stefovska V. Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses. Nat. Neurosci. 2008 11 4 476 487 10.1038/nn2071 18344994
    [Google Scholar]
  81. Behrens M.M. Ali S.S. Dao D.N. Lucero J. Shekhtman G. Quick K.L. Dugan L.L. Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase. Science 2007 318 5856 1645 1647 10.1126/science.1148045
    [Google Scholar]
  82. Behrens M.M. Sejnowski T.J. Does schizophrenia arise from oxidative dysregulation of parvalbumin-interneurons in the developing cortex? Neuropharmacology 2009 57 3 193 200 10.1016/j.neuropharm.2009.06.002 19523965
    [Google Scholar]
  83. Schiavone S. Sorce S. Dubois-Dauphin M. Jaquet V. Colaianna M. Zotti M. Cuomo V. Trabace L. Krause K.H. Involvement of NOX2 in the development of behavioral and pathologic alterations in isolated rats. Biol. Psychiatry 2009 66 4 384 392 10.1016/j.biopsych.2009.04.033 19559404
    [Google Scholar]
  84. McBean G. Cysteine, Glutathione, and thiol redox balance in astrocytes. Antioxidants 2017 6 3 62 75 10.3390/antiox6030062 28771170
    [Google Scholar]
  85. Tosic M. Ott J. Barral S. Bovet P. Deppen P. Gheorghita F. Matthey M.L. Parnas J. Preisig M. Saraga M. Solida A. Timm S. Wang A.G. Werge T. Cuénod M. Quang Do K. Schizophrenia and oxidative stress: Glutamate cysteine ligase modifier as a susceptibility gene. Am. J. Hum. Genet. 2006 79 3 586 592 10.1086/507566 16909399
    [Google Scholar]
  86. Grace A.A. Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression. Nat. Rev. Neurosci. 2016 17 8 524 532 10.1038/nrn.2016.57 27256556
    [Google Scholar]
  87. Hradetzky E. Sanderson T.M. Tsang T.M. Sherwood J.L. Fitzjohn S.M. Lakics V. Malik N. Schoeffmann S. O’Neill M.J. Cheng T.M.K. Harris L.W. Rahmoune H. Guest P.C. Sher E. Collingridge G.L. Holmes E. Tricklebank M.D. Bahn S. The methylazoxymethanol acetate (MAM-E17) rat model: Molecular and functional effects in the hippocampus. Neuropsychopharmacology 2012 37 2 364 377 10.1038/npp.2011.219 21956444
    [Google Scholar]
  88. Fonnum F. Lock E.A. The contributions of excitotoxicity, glutathione depletion and DNA repair in chemically induced injury to neurones: exemplified with toxic effects on cerebellar granule cells. J. Neurochem. 2004 88 3 513 531 10.1046/j.1471‑4159.2003.02211.x 14720201
    [Google Scholar]
  89. Lodge D.J. Grace A.A. Gestational methylazoxymethanol acetate administration: A developmental disruption model of schizophrenia. Behav. Brain Res. 2009 204 2 306 312 10.1016/j.bbr.2009.01.031 19716984
    [Google Scholar]
  90. Moore H. Jentsch J.D. Ghajarnia M. Geyer M.A. Grace A.A. A neurobehavioral systems analysis of adult rats exposed to methylazoxymethanol acetate on E17: Implications for the neuropathology of schizophrenia. Biol. Psychiatry 2006 60 3 253 264 10.1016/j.biopsych.2006.01.003 16581031
    [Google Scholar]
  91. Gill K.M. Grace A.A. Corresponding decrease in neuronal markers signals progressive parvalbumin neuron loss in MAM schizophrenia model. Int. J. Neuropsychopharmacol. 2014 17 10 1609 1619 10.1017/S146114571400056X 24787547
    [Google Scholar]
  92. Du Y. Grace A.A. Loss of parvalbumin in the hippocampus of MAM schizophrenia model rats is attenuated by peripubertal diazepam. Int. J. Neuropsychopharmacol. 2016 19 11 pyw065 10.1093/ijnp/pyw065 27432008
    [Google Scholar]
  93. Phensy A. Driskill C. Lindquist K. Guo L. Jeevakumar V. Fowler B. Du H. Kroener S. Antioxidant treatment in male mice prevents mitochondrial and synaptic changes in an NMDA receptor dysfunction model of schizophrenia. eNeuro 2017 4 4 ENEURO.0081-17.2017 10.1523/ENEURO.0081‑17.2017 28819639
    [Google Scholar]
  94. Cabungcal J.H. Counotte D.S. Lewis E.M. Tejeda H.A. Piantadosi P. Pollock C. Calhoon G.G. Sullivan E.M. Presgraves E. Kil J. Hong L.E. Cuenod M. Do K.Q. O’Donnell P. Juvenile antioxidant treatment prevents adult deficits in a developmental model of schizophrenia. Neuron 2014 83 5 1073 1084 10.1016/j.neuron.2014.07.028 25132466
    [Google Scholar]
  95. Gomes F.V. Grace A.A. Adolescent stress as a driving factor for schizophrenia development - A basic science perspective. Schizophr. Bull. 2017 43 3 486 489 10.1093/schbul/sbx033 28419390
    [Google Scholar]
  96. McCutcheon R.A. Abi-Dargham A. Howes O.D. Schizophrenia, dopamine and the striatum: From biology to symptoms. Trends Neurosci. 2019 42 3 205 220 10.1016/j.tins.2018.12.004 30621912
    [Google Scholar]
  97. Howes O.D. Bukala B.R. Beck K. Schizophrenia: From neurochemistry to circuits, symptoms and treatments. Nat. Rev. Neurol. 2024 20 1 22 35 10.1038/s41582‑023‑00904‑0 38110704
    [Google Scholar]
  98. McCutcheon R.A. Keefe R.S.E. McGuire P.K. Cognitive impairment in schizophrenia: Aetiology, pathophysiology, and treatment. Mol. Psychiatry 2023 28 5 1902 1918 10.1038/s41380‑023‑01949‑9 36690793
    [Google Scholar]
  99. Sonnenschein S.F. Gomes F.V. Grace A.A. Dysregulation of midbrain dopamine system and the pathophysiology of schizophrenia. Front. Psychiatry 2020 11 613 10.3389/fpsyt.2020.00613 32719622
    [Google Scholar]
  100. Lodge D.J. Grace A.A. The laterodorsal tegmentum is essential for burst firing of ventral tegmental area dopamine neurons. Proc. Natl. Acad. Sci. USA 2006 103 13 5167 5172 10.1073/pnas.0510715103 16549786
    [Google Scholar]
  101. Floresco S.B. West A.R. Ash B. Moore H. Grace A.A. Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission. Nat. Neurosci. 2003 6 9 968 973 10.1038/nn1103 12897785
    [Google Scholar]
  102. Grace A.A. Gomes F.V. The circuitry of dopamine system regulation and its disruption in schizophrenia: Insights into treatment and prevention. Schizophr. Bull. 2019 45 1 148 157 10.1093/schbul/sbx199 29385549
    [Google Scholar]
  103. Fuente-Sandoval C. León-Ortiz P. Favila R. Stephano S. Mamo D. Ramírez-Bermúdez J. Graff-Guerrero A. Higher levels of glutamate in the associative-striatum of subjects with prodromal symptoms of schizophrenia and patients with first-episode psychosis. Neuropsychopharmacology 2011 36 9 1781 1791 10.1038/npp.2011.65 21508933
    [Google Scholar]
  104. de la Fuente-Sandoval C. León-Ortiz P. Azcárraga M. Stephano S. Favila R. Díaz-Galvis L. Alvarado-Alanis P. Ramírez-Bermúdez J. Graff-Guerrero A. Glutamate levels in the associative striatum before and after 4 weeks of antipsychotic treatment in first-episode psychosis: a longitudinal proton magnetic resonance spectroscopy study. JAMA Psychiatry 2013 70 10 1057 1066 10.1001/jamapsychiatry.2013.289 23966023
    [Google Scholar]
  105. Heckers S. Rauch S. Goff D. Savage C. Schacter D. Fischman A. Alpert N. Impaired recruitment of the hippocampus during conscious recollection in schizophrenia. Nat. Neurosci. 1998 1 4 318 323 10.1038/1137 10195166
    [Google Scholar]
  106. McHugo M. Talati P. Armstrong K. Vandekar S.N. Blackford J.U. Woodward N.D. Heckers S. Hyperactivity and reduced activation of anterior hippocampus in early psychosis. Am. J. Psychiatry 2019 176 12 1030 1038 10.1176/appi.ajp.2019.19020151 31623459
    [Google Scholar]
  107. Zimmerman E.C. Grace A.A. The nucleus reuniens of the midline thalamus gates prefrontal-hippocampal modulation of ventral tegmental area dopamine neuron activity. J. Neurosci. 2016 36 34 8977 8984 10.1523/JNEUROSCI.1402‑16.2016 27559178
    [Google Scholar]
  108. Zimmerman E.C. Grace A.A. Prefrontal cortex modulates firing pattern in the nucleus reuniens of the midline thalamus via distinct corticothalamic pathways. Eur. J. Neurosci. 2018 48 10 3255 3272 10.1111/ejn.14111 30107061
    [Google Scholar]
  109. Steullet P. Cabungcal J-H. Bukhari S.A. Ardelt M.I. Pantazopoulos H. Hamati F. Salt T.E. Cuenod M. Do K.Q. Berretta S. The thalamic reticular nucleus in schizophrenia and bipolar disorder: Role of parvalbumin-expressing neuron networks and oxidative stress. Mol. Psychiatry 2018 23 10 2057 2065 10.1038/mp.2017.230 29180672
    [Google Scholar]
  110. Zhu X. Cabungcal J.H. Cuenod M. Uliana D.L. Do K.Q. Grace A.A. Thalamic reticular nucleus impairments and abnormal prefrontal control of dopamine system in a developmental model of schizophrenia: prevention by N-acetylcysteine. Mol. Psychiatry 2021 26 12 7679 7689 10.1038/s41380‑021‑01198‑8 34193975
    [Google Scholar]
  111. Grace A.A. Uliana D.L. Insights into the mechanism of action of antipsychotic drugs derived from animal models: Standard of care versus novel targets. Int. J. Mol. Sci. 2023 24 15 12374 10.3390/ijms241512374 37569748
    [Google Scholar]
  112. Kaar S.J. Natesan S. McCutcheon R. Howes O.D. Antipsychotics: Mechanisms underlying clinical response and side-effects and novel treatment approaches based on pathophysiology. Neuropharmacology 2020 172 107704 10.1016/j.neuropharm.2019.107704 31299229
    [Google Scholar]
  113. Sonnenschein S.F. Gill K.M. Grace A.A. State-dependent effects of the D2 partial agonist aripiprazole on dopamine neuron activity in the MAM neurodevelopmental model of schizophrenia. Neuropsychopharmacology 2019 44 3 572 580 10.1038/s41386‑018‑0219‑1 30267014
    [Google Scholar]
  114. Paul S.M. Yohn S.E. Popiolek M. Miller A.C. Felder C.C. Miller A.C. Ph D. Felder C.C. Ph D. Muscarinic acetylcholine receptor agonists as novel treatments for schizophrenia. Am. J. Psychiatry 2022 179 9 611 627 10.1176/appi.ajp.21101083 35758639
    [Google Scholar]
  115. Paul S.M. Yohn S.E. Brannan S.K. Neugebauer N.M. Breier A. Muscarinic receptor activators as novel treatments for schizophrenia. Biol. Psychiatry 2024 96 8 627 637 10.1016/j.biopsych.2024.03.014 38537670
    [Google Scholar]
  116. Shekhar A. Potter W.Z. Lightfoot J. Lienemann J. Dubé S. Mallinckrodt C. Bymaster F.P. McKinzie D.L. Felder C.C. Ph D. Bymaster F.P. Sc M. Mckinzie D.L. Ph D. Felder C.C. Ph D. Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am. J. Psychiatry 2008 165 8 1033 1039 10.1176/appi.ajp.2008.06091591 18593778
    [Google Scholar]
  117. Jeon J. Dencker D. Wörtwein G. Woldbye D.P.D. Cui Y. Davis A.A. Levey A.I. Schütz G. Sager T.N. Mørk A. Li C. Deng C.X. Fink-Jensen A. Wess J. A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors. J. Neurosci. 2010 30 6 2396 2405 10.1523/JNEUROSCI.3843‑09.2010 20147565
    [Google Scholar]
  118. Foster D.J. Wilson J.M. Remke D.H. Mahmood M.S. Uddin M.J. Wess J. Patel S. Marnett L.J. Niswender C.M. Jones C.K. Xiang Z. Lindsley C.W. Rook J.M. Conn P.J. Antipsychotic-like effects of M 4 positive allosteric modulators are mediated by CB 2 receptor-dependent inhibition of dopamine release. Neuron 2016 91 6 1244 1252 10.1016/j.neuron.2016.08.017 27618677
    [Google Scholar]
  119. Gomes F.V. Grace A.A. Beyond dopamine receptor antagonism: New targets for schizophrenia treatment and prevention. Int. J. Mol. Sci. 2021 22 9 4467 10.3390/ijms22094467 33922888
    [Google Scholar]
  120. Kohlmeier K.A. Ishibashi M. Wess J. Bickford M.E. Leonard C.S. Knockouts reveal overlapping functions of M 2 and M 4 muscarinic receptors and evidence for a local glutamatergic circuit within the laterodorsal tegmental nucleus. J. Neurophysiol. 2012 108 10 2751 2766 10.1152/jn.01120.2011 22956788
    [Google Scholar]
  121. Kohlmeier K.A. Kristiansen U. GABAergic actions on cholinergic laterodorsal tegmental neurons: implications for control of behavioral state. Neuroscience 2010 171 3 812 829 10.1016/j.neuroscience.2010.09.034 20884335
    [Google Scholar]
  122. Fernandez S.P. Broussot L. Marti F. Contesse T. Mouska X. Soiza-Reilly M. Marie H. Faure P. Barik J. Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors. Nat. Commun. 2018 9 1 4449 10.1038/s41467‑018‑06809‑7 30361503
    [Google Scholar]
  123. Barik J. Marti F. Morel C. Fernandez SP. Chronic stress triggers social aversion via glucocorticoid receptor in dopaminoceptive neurons. Science 2013 339 6117 332 335 10.1126/science.1226767
    [Google Scholar]
  124. Kohlmeier K.A. Vardar B. Christensen M.H. γ-Hydroxybutyric acid induces actions via the GABAB receptor in arousal and motor control-related nuclei: Implications for therapeutic actions in behavioral state disorders. Neuroscience 2013 248 261 277 10.1016/j.neuroscience.2013.06.011 23791974
    [Google Scholar]
  125. Madden T.E. Johnson S.W. Gamma-hydroxybutyrate is a GABAB receptor agonist that increases a potassium conductance in rat ventral tegmental dopamine neurons. J. Pharmacol. Exp. Ther. 1998 287 1 261 265 10.1016/S0022‑3565(24)37787‑0 9765346
    [Google Scholar]
  126. Labouèbe G. Lomazzi M. Cruz H.G. Creton C. Luján R. Li M. Yanagawa Y. Obata K. Watanabe M. Wickman K. Boyer S.B. Slesinger P.A. Lüscher C. RGS2 modulates coupling between GABAB receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Nat. Neurosci. 2007 10 12 1559 1568 10.1038/nn2006 17965710
    [Google Scholar]
  127. Erhardt S. Andersson B. Nissbrandt H. Engberg G. Inhibition of firing rate and changes in the firing pattern of nigral dopamine neurons by γ-hydroxybutyric acid (GHBA) are specifically induced by activation of GABAB receptors. Naunyn Schmiedebergs Arch. Pharmacol. 1998 357 6 611 619 10.1007/PL00005215 9686936
    [Google Scholar]
  128. Feigenbaum J.J. Howard S. Naloxone reverses the inhibitory effect of gammahydroxybutyrate on central DA release. Neurosci. Lett. 1997 224 1 71 74 9132694
    [Google Scholar]
  129. Gessa G.L. Vargiu L. Crabai F. Boero G.C. Caboni F. Camba R. Selective increase of brain dopamine induced by gamma-hydroxybutyrate. Life Sci. 1966 5 21 1921 1930 10.1016/0024‑3205(66)90261‑X
    [Google Scholar]
  130. Walters J.R. Roth R.H. Effect of gamma-hydroxybutyrate on dopamine and dopamine metabolites in the rat striatum. Biochem. Pharmacol. 1972 21 15 2111 2121 10.1016/0006‑2952(72)90164‑5 4645883
    [Google Scholar]
  131. Feigenbaum J. Yanai J. Klawans H. Moon B. Differential catecholamine uptake inhibition as a possible mode of action of D-amphetamine induced locomotor activity. Res. Commun. Chem. Pathol. Pharmacol. 1983 39 2 349 352 6844751
    [Google Scholar]
  132. Kusljic S. van den Buuse M. Gogos A. Reassessment of amphetamine- and phencyclidine-induced locomotor hyperactivity as a model of psychosis-like behavior in rats. J. Integr. Neurosci. 2022 21 1 17 10.31083/j.jin2101017 35164453
    [Google Scholar]
  133. Gatley S.J. Volkow N.D. Fowler J.S. Dewey S.L. Logan J. Medical S.J.G. Chemistry J.S.F. Departments J.L. Sensitivity of striatal [11C]cocaine binding to decreases in synaptic dopamine. Synapse 1995 20 2 137 144 10.1002/syn.890200207 7570343
    [Google Scholar]
  134. Ross S. Jackson D. Kinetic properties of the accumulation of 3H-raclopride in the mouse brain in vivo. Naunyn Schmiedebergs Arch. Pharmacol. 1989 340 1 6 12 10.1007/BF00169199 2797215
    [Google Scholar]
  135. Kish S.J. O’Leary G. Mamelak M. McCluskey T. Warsh J.J. Shapiro C. Bies R. Yu Y. Pollock B. Tong J. Boileau I. Does sodium oxybate inhibit brain dopamine release in humans? An exploratory neuroimaging study. Hum. Psychopharmacol. 2021 36 5 e2791 10.1002/hup.2791 33899252
    [Google Scholar]
  136. Williams J.A. Comisarow J. Day J. Fibiger H.C. Reiner P.B. State-dependent release of acetylcholine in rat thalamus measured by in vivo microdialysis. J. Neurosci. 1994 14 9 5236 5242 10.1523/JNEUROSCI.14‑09‑05236.1994 8083733
    [Google Scholar]
  137. Steriade M. Datta S. Paré D. Oakson G. Curró Dossi R.C. Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems. J. Neurosci. 1990 10 8 2541 2559 10.1523/JNEUROSCI.10‑08‑02541.1990 2388079
    [Google Scholar]
  138. Steriade M. McCormick D.A. Sejnowski T.J. Thalamocortical oscillations in the sleeping and aroused brain. Science 1993 262 5134 679 685 10.1126/science.8235588 8235588
    [Google Scholar]
  139. Juhász G. Emri Z. Kékesi K.A. Salfay O. Crunelli V. Blockade of thalamic GABAB receptors decreases EEG synchronization. Neurosci. Lett. 1994 172 1-2 155 158 10.1016/0304‑3940(94)90685‑8 8084524
    [Google Scholar]
  140. Williams S.R. Turner J.P. Crunelli V. Gamma-hydroxybutyrate promotes oscillatory activity of rat and cat thalamocortical neurons by a tonic GABAB receptor-mediated hyperpolarization. Neuroscience 1995 66 1 133 141 10.1016/0306‑4522(94)00604‑4 7637863
    [Google Scholar]
  141. Ferrarelli F. Sleep Abnormalities in Schizophrenia: State of the Art and Next Steps. Am. J. Psychiatry 2021 178 10 903 913 10.1176/appi.ajp.2020.20070968 33726524
    [Google Scholar]
  142. Cohen S. Goldsmith D.R. Ning C.S. Addington J. Bearden C.E. Cadenhead K.S. Cannon T.D. Cornblatt B.A. Keshavan M. Mathalon D.H. Perkins D.O. Seidman L.J. Stone W.S. Tsuang M.T. Woods S.W. Walker E.F. Miller B.J. Sleep disturbance, suicidal ideation and psychosis-risk symptoms in individuals at clinical high risk for psychosis. Psychiatry Res. 2024 341 116147 10.1016/j.psychres.2024.116147 39197223
    [Google Scholar]
  143. Ferrarelli F. Sleep spindles as neurophysiological biomarkers of schizophrenia. Eur. J. Neurosci. 2024 59 8 1907 1917 10.1111/ejn.16178 37885306
    [Google Scholar]
  144. Kaskie R.E. Gill K.M. Ferrarelli F. Reduced frontal slow wave density during sleep in first-episode psychosis. Schizophr. Res. 2019 206 318 324 10.1016/j.schres.2018.10.024 30377012
    [Google Scholar]
  145. Poe S.L. Brucato G. Bruno N. Arndt L.Y. Ben-David S. Gill K.E. Colibazzi T. Kantrowitz J.T. Corcoran C.M. Girgis R.R. Sleep disturbances in individuals at clinical high risk for psychosis. Psychiatry Res. 2017 249 240 243 10.1016/j.psychres.2016.12.029 28126579
    [Google Scholar]
  146. Ayers N. McCall W.V. Miller B.J. Sleep problems, suicidal ideation, and psychopathology in first-episode psychosis. Schizophr. Bull. 2024 50 2 286 294 10.1093/schbul/sbad045 37086485
    [Google Scholar]
  147. Kantrowitz J.T. Oakman E. Bickel S. Citrome L. Spielman A. Silipo G. Battaglia J. Javitt D.C. The importance of a good night’s sleep: An open-label trial of the sodium salt of γ-hydroxybutyric acid in insomnia associated with schizophrenia. Schizophr. Res. 2010 120 1-3 225 226 10.1016/j.schres.2010.03.035 20435443
    [Google Scholar]
  148. Lataster J. Myin-Germeys I. Lieb R. Wittchen H.U. van Os J. Adversity and psychosis: A 10‐year prospective study investigating synergism between early and recent adversity in psychosis. Acta Psychiatr. Scand. 2012 125 5 388 399 10.1111/j.1600‑0447.2011.01805.x 22128839
    [Google Scholar]
  149. Gomes F. Grace A. Prefrontal cortex dysfunction increases susceptibility to schizophrenia-like changes induced by adolescent stress exposure. Schizophr. Bull. 2017 43 3 S248 10.1093/schbul/sbx022.097 28003467
    [Google Scholar]
  150. Walker E.F. Trotman H.D. Pearce B.D. Addington J. Cadenhead K.S. Cornblatt B.A. Heinssen R. Mathalon D.H. Perkins D.O. Seidman L.J. Tsuang M.T. Cannon T.D. McGlashan T.H. Woods S.W. Cortisol levels and risk for psychosis: Initial findings from the North American prodrome longitudinal study. Biol. Psychiatry 2013 74 6 410 417 10.1016/j.biopsych.2013.02.016 23562006
    [Google Scholar]
  151. Dornbierer D.A. Boxler M. Voegel C.D. Stucky B. Steuer A.E. Binz T.M. Baumgartner M.R. Baur D.M. Quednow B.B. Kraemer T. Seifritz E. Landolt H.P. Bosch O.G. Nocturnal gamma-hydroxybutyrate reduces cortisol-awakening response and morning kynurenine pathway metabolites in healthy volunteers. Int. J. Neuropsychopharmacol. 2019 22 10 631 639 10.1093/ijnp/pyz047 31504554
    [Google Scholar]
  152. Nava F. Premi S. Manzato E. Campagnola W. Lucchini A. Gessa G.L. Gamma-hydroxybutyrate reduces both withdrawal syndrome and hypercortisolism in severe abstinent alcoholics: An open study vs. diazepam. Am. J. Drug Alcohol Abuse 2007 33 3 379 392 10.1080/00952990701315046 17613965
    [Google Scholar]
  153. Paquin V. Lapierre M. Veru F. King S. Early environmental upheaval and the risk for schizophrenia. Annu. Rev. Clin. Psychol. 2021 17 1 285 311 10.1146/annurev‑clinpsy‑081219‑103805 33544627
    [Google Scholar]
  154. Popovic D. Schmitt A. Kaurani L. Senner F. Papiol S. Malchow B. Fischer A. Schulze T.G. Koutsouleris N. Falkai P. Childhood trauma in schizophrenia: Current findings and research perspectives. Front. Neurosci. 2019 13 274 10.3389/fnins.2019.00274 30983960
    [Google Scholar]
  155. Hertz L. Rothman D.L. Glucose, lactate, β-hydroxybutyrate, acetate, GABA, and succinate as substrates for synthesis of glutamate and GABA in the glutamine–glutamate/GABA cycle. The Glutamate/GABA-Glutamine Cycle Cham Springer Schousboe A. Sonnewald U. 2016 9 42 10.1007/978‑3‑319‑45096‑4_2
    [Google Scholar]
  156. Kaufman E.E. Metabolism and distribution of gammahydroxybutyrate in the brain. Gammahydroxybutyrate: Molecular, Functional and Clinival Aspects London and New York Taylor and Francis Tunnicliff G. Cash C.D 2002
    [Google Scholar]
  157. Yung J.H.M. Yeung L.S.N. Ivovic A. Tan Y.F. Jentz E.M. Batchuluun B. Gohil H. Wheeler M.B. Joseph J.W. Giacca A. Mamelak M. Prevention of lipotoxicity in pancreatic islets with gammahydroxybutyrate. Cells 2022 11 3 545 10.3390/cells11030545 35159354
    [Google Scholar]
  158. Haller C. Mende M. Schuier F. Schuh R. Schröck H. Kuschinsky W. Effect of γ-hydroxybutyrate on local and global glucose metabolism in the anesthetized cat brain. J. Cereb. Blood Flow Metab. 1990 10 4 493 498 10.1038/jcbfm.1990.91 2347880
    [Google Scholar]
  159. Dienel S.J. Enwright J.F. Hoftman G.D. Lewis D.A. Markers of glutamate and GABA neurotransmission in the prefrontal cortex of schizophrenia subjects: Disease effects differ across anatomical levels of resolution. Schizophr. Res. 2020 217 86 94 10.1016/j.schres.2019.06.003 31296415
    [Google Scholar]
  160. Veeraiah P. Noronha J.M. Maitra S. Bagga P. Khandelwal N. Chakravarty S. Kumar A. Patel A.B. Dysfunctional glutamatergic and γ-aminobutyric acidergic activities in prefrontal cortex of mice in social defeat model of depression. Biol. Psychiatry 2014 76 3 231 238 10.1016/j.biopsych.2013.09.024 24239130
    [Google Scholar]
  161. Ferraro L. Tanganelli S. O’Connor W.T. Francesconi W. Loche A. Gessa G.L. Antonelli T. γ‐Hydroxybutyrate modulation of glutamate levels in the hippocampus: An in vivo and in vitro study. J. Neurochem. 2001 78 5 929 939 10.1046/j.1471‑4159.2001.00530.x 11553667
    [Google Scholar]
  162. Dornbierer D.A. Zölch N. Baur D.M. Hock A. Stucky B. Quednow B.B. Kraemer T. Seifritz E. Bosch O.G. Landolt H.P. Nocturnal sodium oxybate increases the anterior cingulate cortex magnetic resonance glutamate signal upon awakening. J. Sleep Res. 2023 32 4 e13866 10.1111/jsr.13866 36869598
    [Google Scholar]
  163. Feigenson K.A. Kusnecov A.W. Silverstein S.M. Inflammation and the two-hit hypothesis of schizophrenia. Neurosci. Biobehav. Rev. 2014 38 72 93 10.1016/j.neubiorev.2013.11.006 24247023
    [Google Scholar]
  164. Germann M. Brederoo S.G. Sommer I.E.C. Abnormal synaptic pruning during adolescence underlying the development of psychotic disorders. Curr. Opin. Psychiatry 2021 34 3 222 227 10.1097/YCO.0000000000000696 33560023
    [Google Scholar]
  165. Kuhn S.A. van Landeghem F.K.H. Zacharias R. Färber K. Rappert A. Pavlovic S. Hoffmann A. Nolte C. Kettenmann H. Microglia express GABA B receptors to modulate interleukin release. Mol. Cell. Neurosci. 2004 25 2 312 322 10.1016/j.mcn.2003.10.023 15019947
    [Google Scholar]
  166. Crunelli V. Leresche N Action of γ-hydroxybutyrate on neuronal excitability and underlying membrane conductances. Gamma-Hydroxybutyrate London and New York Taylor and Francis Tunnicliff G. Cash C.D 2002 75 110
    [Google Scholar]
  167. Klein C. Kemmel V. Taleb O. Aunis D. Maitre M. Pharmacological doses of gamma-hydroxybutyrate (GHB) potentiate histone acetylation in the rat brain by histone deacetylase inhibition. Neuropharmacology 2009 57 2 137 147 10.1016/j.neuropharm.2009.04.013 19427877
    [Google Scholar]
  168. Leus N.G.J. Zwinderman M.R.H. Dekker F.J. Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-κB-mediated inflammation. Curr. Opin. Chem. Biol. 2016 33 160 168 10.1016/j.cbpa.2016.06.019 27371876
    [Google Scholar]
  169. Xia M. Zhao Q. Zhang H. Chen Y. Yuan Z. Xu Y. Zhang M. Proteomic Analysis of HDAC3 Selective Inhibitor in the Regulation of Inflammatory Response of Primary Microglia. Neural Plast. 2017 2017 1 13 10.1155/2017/6237351 28293439
    [Google Scholar]
  170. Subburaju S. Coleman A.J. Cunningham M.G. Ruzicka W.B. Benes F.M. Epigenetic regulation of glutamic acid decarboxylase 67 in a hippocampal circuit. Cereb. Cortex 2017 27 11 5284 5293 10.1093/cercor/bhw307 27733539
    [Google Scholar]
/content/journals/cn/10.2174/011570159X377481250526110256
Loading
Can Sodium Oxybate Mitigate the Symptoms of Schizophrenia?
Bentham Science Publishers ; https://doi.org/10.2174/011570159X377481250526110256
/content/journals/cn/10.2174/011570159X377481250526110256
/content/journals/cn/10.2174/011570159X377481250526110256
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: psychological stress ; dopaminergic antagonist ; glutamate ; GABA ; sleep ; Schizophrenia ; oxidative stress ; cholinergic agonist ; sodium oxybate

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test