Experimental Brain Research

, Volume 168, Issue 4, pp 587–590 | Cite as

Increased density of GABAA receptors in the superior temporal gyrus in schizophrenia

  • Chao DengEmail author
  • Xu-Feng Huang
Research Note


The superior temporal gyrus (STG) is strongly implicated in the pathophysiology of schizophrenia, particularly with regards to auditory hallucinations. In a previous study we reported a decrease in the density of M1 and M2/M4 muscarinic receptors in the STG in schizophrenia. In this study, we investigated the density of GABAA receptors in the left STG of schizophrenia patients compared to control subjects. We used quantitative autoradiography to investigate the binding of the agonist [3H] muscimol to GABAA receptors in the STG. A significantly higher density of [3H] muscimol binding was observed in the upper three quarters of the STG grey matter (corresponding to layers I–IV) than in the lower one-quarter (layers V–VI) in both groups. A significant increase (about 30%, P<0.05) in binding of [3H] muscimol was clearly observed in schizophrenia patients compared to control subjects. There were no significant correlations between [3H] muscimol binding density and age, post-mortem interval, brain pH or final recorded antipsychotic drug use. These results suggest an increase of GABAA receptor densities in the STG of schizophrenia patients.


Schizophrenia GABA receptor Autoradiography Superior temporal gyrus  



Tissues were received from the NSW Tissue Resource Centre which is supported by The University of Sydney, the Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), the National Institute of Alcohol Abuse and Alcoholism and the NSW Department of Health. This work was supported by a University of Wollongong URC grant to C. Deng and NISAD, utilising infrastructure funding from NSW Health.


  1. Baur R, Sigel E (2003) On high- and low-affinity agonist sites in GABAA receptors. J Neurochem 87:325–332CrossRefPubMedGoogle Scholar
  2. Benes FM, Berretta S (2001) GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 25:1–27CrossRefPubMedGoogle Scholar
  3. Benes FM, Sorensen I, Vincent SL, Bird ED, Sathi M (1992a) Increased density of glutamate-immunoreactive vertical processes in superficial laminae in cingulate cortex of schizophrenic brain. Cereb Cortex 2:503–512PubMedCrossRefGoogle Scholar
  4. Benes FM, Vincent SL, Alsterberg G, Bird ED, SanGiovanni JP (1992b) Increased GABAA receptor binding in superficial layers of cingulate cortex in schizophrenics. J Neurosci 12:924–929PubMedGoogle Scholar
  5. Benes FM, Vincent SL, Marie A, Khan Y (1996) Up-regulation of GABAA receptor binding on neurons of the prefrontal cortex in schizophrenic subjects. Neuroscience 75:1021–1031CrossRefPubMedGoogle Scholar
  6. Benes FM, Wickramasinghe R, Vincent SL, Khan Y, Todtenkopf M (1997) Uncoupling of GABA(A) and benzodiazepine receptor binding activity in the hippocampal formation of schizophrenic brain. Brain Res 755:121–129CrossRefPubMedGoogle Scholar
  7. Cotter D, Landau S, Beasley C, Stevenson R, Chana G, MacMillan L, Everall I (2002) The density and spatial distribution of GABAergic neurons, labelled using calcium binding proteins, in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia. Biol Psychiatry 51:377–386CrossRefPubMedGoogle Scholar
  8. Dean B, Hussain T, Hayes W, Scarr E, Kitsoulis S, Hill C, Opeskin K, Copolov DL (1999) Changes in serotonin2A and GABA(A) receptors in schizophrenia: studies on the human dorsolateral prefrontal cortex. J Neurochem 72:1593–1599PubMedCrossRefGoogle Scholar
  9. Deng C, Huang X-F (2005) Decreased density of muscarinic receptors in the superior temporal gyrus in schizophrenia. J Neurosci Res 81:883–890CrossRefPubMedGoogle Scholar
  10. Farnbach-Pralong D, Bradbury R, Copolov D, Dean B (1998) Clozapine and olanzapine treatment decreases rat cortical and limbic GABA(A) receptors. Eur J Pharmacol 349:22CrossRefGoogle Scholar
  11. Gaser C, Nenadic I, Volz HP, Buchel C, Sauer H (2004) Neuroanatomy of “hearing voices”: a frontotemporal brain structural abnormality associated with auditory hallucinations in schizophrenia. Cereb Cortex 14:91–96CrossRefPubMedGoogle Scholar
  12. Hashimoto T, Shu H, Kuriyama K (1994) Muscarinic M1 receptor mediated inhibition of GABA release from rat cerebral cortex. Neurochem Int 24:389–394CrossRefPubMedGoogle Scholar
  13. Hashimoto T, Volk DW, Eggan SM, Mirnics K, Pierri JN, Sun Z, Sampson AR, Lewis DA (2003) Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. J Neurosci 23:6315–6326PubMedGoogle Scholar
  14. Impagnatiello F, Guidotti AR, Pesold C, Dwivedi Y, Caruncho H, Pisu MG, Uzunov DP, Smalheiser NR, Davis JM, Pandey GN, Pappas GD, Tueting P, Sharma RP, Costa E (1998) A decrease of reelin expression as a putative vulnerability factor in schizophrenia. In: Proceedings of the National Academy of Sciences of the United States of America, vol 95, pp 15718–15723Google Scholar
  15. Jablensky A, Hugler H, von Vranach M, Kalinov K (1993) Kraepelin revisited: a reassessment and statistical analysis of dementia praecox and manic-depressive insanity in 1908. Psychol Med 23:843–858PubMedCrossRefGoogle Scholar
  16. Keks N, Hill C, Opeskin K, Copolov D, Dean B (1999) Psychiatric diagnosis after death: the problems of accurate diagnosis. In: Dean B, Hyde TM, Kleinmam JE (eds) The use of CNS autopsy tissue in psychiatric research: a practical guide. Gordon & Breach Science Publishers, Sydney, pp 19–37Google Scholar
  17. Kim JJ, Crespo-Facorro B, Andreasen NC, O’Leary DS, Magnotta V, Nopoulos P (2003) Morphology of the lateral superior temporal gyrus in neuroleptic nai;ve patients with schizophrenia: relationship to symptoms. Schizophr Res 60:173–181PubMedGoogle Scholar
  18. Kiuchi Y, Kobayashi T, Takeuchi J, Shimizu H, Ogata H, Toru M (1989) Benzodiazepine receptors increase in post-mortem brain of chronic schizophrenics. Eur Arch Psychiatry Neurol Sci 239:71–78CrossRefPubMedGoogle Scholar
  19. Lewis DA, Hashimoto T, Volk DW (2005) Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 6:312–324CrossRefPubMedGoogle Scholar
  20. Pandey GN, Conley RR, Pandey SC, Goel S, Roberts RC, Tamminga CA, Chute D, Smialek J (1997) Benzodiazepine receptors in the post-mortem brain of suicide victims and schizophrenic subjects. Psychiatry Res 71:137–149CrossRefPubMedGoogle Scholar
  21. Rudolph U, Crestani F, Mohler H (2001) GABAA receptor subtypes: dissecting their pharmacological functions. Trends Pharmacol Sci 22:188–194CrossRefPubMedGoogle Scholar
  22. Silbersweig DA, Stern E, Frith C, Cahill C, Holmes A, Grootoonk S, Seaward J, McKenna P, Chua SE, Schnorr L, Johnes T, Frackowiak RSJ (1995) A functional neuroanatomy of hallucination in schizophrenia. Nature 378:176–179PubMedCrossRefGoogle Scholar
  23. Smith GB, Olsen RW (1995) Functional domains of GABAA receptors. Trends Pharmacol Sci 16:162–168CrossRefPubMedGoogle Scholar
  24. Squires RF, Lajtha A, Saederup E, Palkovits M (1993) Reduced [3H] flunitrazepam binding in cingulate cortex and hippocampus of postmortem schizophrenic brains: is selective loss of glutamatergic neurons associated with major psychoses? Neurochem Res 18:219–223PubMedCrossRefGoogle Scholar
  25. Van der Zee EA, Luiten PGM (1999) Muscarinic acetylcholine receptors in the hippocampus, neocortex and amygdala: a review of immunocytochemical localization in relation to learning and memory. Prog Neurobiol 58:409–471CrossRefPubMedGoogle Scholar
  26. Wassef A, Baker J, Kochan LD (2003) GABA and schizophrenia: a review of basic science and clinical studies. J Clin Psychopharmacol 23:601–640CrossRefPubMedGoogle Scholar
  27. Woo TU, Whitehead RE, Melchitzky DS, Lewis DA (1998) A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia. In: Proceedings of the National Academy of Sciences of the United States of America, vol 95, pp 5341–5346Google Scholar
  28. Woo TU, Walsh JP, Benes FM (2004) 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. Arc Gen Psychiatry 61:649–657CrossRefGoogle Scholar
  29. Zilles K, Werner L, Qu M, Schleicher A, Gross G (1991) Quantitative autoradiography of 11 different transmitter binding sites in the basal forebrain region of the rat-evidence of heterogeneity in distribution pattern. Neuroscience 42:473–487CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Department of Biomedical ScienceUniversity of WollongongWollongongAustralia
  2. 2.Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD)SydneyAustralia

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