GABAergic system impairment in the hippocampus and superior temporal gyrus of patients with paranoid schizophrenia: A post-mortem study

Schizophrenia Research

Volumn 177, Issue 1-3, 2016, Pages 10-17

  Steiner, Johann ^a,c   Brisch, Ralf ^b   Schiltz, Kolja ^a,c   Dobrowolny, Henrik ^a   Mawrin, Christian ^a   Krzyżanowska, Marta ^b   Bernstein, Hans Gert ^a   Jankowski, Zbigniew ^b   Braun, Katharina ^a,c   Schmitt, Andrea ^d,e   Bogerts, Bernhard ^a,c   Gos, Tomasz ^a,b  

^a OTTO VON GUERICKE UNIVERSITY   (Germany)

^b MEDICAL UNIVERSITY OF GDANSK   (Poland)

^c Center for Behavioral Brain Sciences   (Germany)

^d LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^e UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

GAD 65 67; Paranoid; Post mortem; Residual; Schizophrenia

Indexed keywords

4 AMINOBUTYRIC ACID; GLUTAMATE DECARBOXYLASE; GLUTAMATE DECARBOXYLASE 65; GLUTAMATE DECARBOXYLASE 67; NEUROLEPTIC AGENT; GLUTAMATE DECARBOXYLASE 1; GLUTAMATE DECARBOXYLASE 2;

ACUTE RESPIRATORY FAILURE; ADULT; AORTA ANEURYSM; ARTICLE; ARTIFICIAL NEURAL NETWORK; ASPHYXIA; ASTHMA; AUTOPSY; BRAIN FUNCTION; CELL DENSITY; CLINICAL ARTICLE; CONTROLLED STUDY; DENTATE GYRUS; FEMALE; GABAERGIC SYSTEM; GABAERGIC TRANSMISSION; GASTROINTESTINAL HEMORRHAGE; HEART FAILURE; HIPPOCAMPAL CA1 REGION; HIPPOCAMPUS; HUMAN; HUMAN TISSUE; ILEUS; IMMUNOHISTOCHEMISTRY; IMMUNOMODULATION; IMMUNOREACTIVITY; LATERODORSAL THALAMIC NUCLEUS; LUNG EMBOLISM; MACROGLIA; MALE; MICROGLIA; NERVE CELL PLASTICITY; NEUROPIL; PARANOID SCHIZOPHRENIA; PERITONITIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; QUANTITATIVE ANALYSIS; RESIDUAL SCHIZOPHRENIA; SCHIZOPHRENIA; SUPERIOR TEMPORAL GYRUS; THALAMUS NUCLEUS; AGED; COHORT ANALYSIS; DRUG EFFECTS; METABOLISM; MIDDLE AGED; TEMPORAL LOBE; THALAMUS DORSOMEDIAL NUCLEUS;

ADULT; AGED; ANTIPSYCHOTIC AGENTS; CA1 REGION, HIPPOCAMPAL; COHORT STUDIES; FEMALE; GLUTAMATE DECARBOXYLASE; HUMANS; IMMUNOHISTOCHEMISTRY; MALE; MEDIODORSAL THALAMIC NUCLEUS; MIDDLE AGED; NEUROPIL; SCHIZOPHRENIA, PARANOID; TEMPORAL LOBE;

EID: 84959105976     PISSN: 09209964     EISSN: 15732509     Source Type: Journal    
DOI: 10.1016/j.schres.2016.02.018     Document Type: Article

References (63)

1. Akbarian, S., Huang, H.S., Molecular and cellular mechanisms of altered GAD1/GAD67 expression in schizophrenia and related disorders. Brain Res. Rev. 52:2 (2006), 293–304.
2. Atkins, M., Burgess, A., Bottomley, C., Riccio, M., Chlorpromazine equivalents: a consensus of opinion for both clinical and research applications. Psychiatr. Bull. 21 (1997), 224–226.
3. Bakker, A., Krauss, G.L., Albert, M.S., Speck, C.L., Jones, L.R., Stark, C.E., Yassa, M.A., Bassett, S.S., Shelton, A.L., Gallagher, M., Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron 74:3 (2012), 467–474.
4. Becker, T., Elmer, K., Schneider, F., Schneider, M., Grodd, W., Bartels, M., Heckers, S., Beckmann, H., Confirmation of reduced temporal limbic structure volume on magnetic resonance imaging in male patients with schizophrenia. Psychiatry Res. 67:2 (1996), 135–143.
5. Behrens, M.M., Sejnowski, T.J., Does schizophrenia arise from oxidative dysregulation of parvalbumin-interneurons in the developing cortex?. Neuropharmacology 57:3 (2009), 193–200.
6. Benes, F.M., Evidence for altered trisynaptic circuitry in schizophrenic hippocampus. Biol. Psychiatry 46:5 (1999), 589–599.
7. Bernstein, H.G., Steiner, J., Guest, P.C., Dobrowolny, H., Bogerts, B., Glial cells as key players in schizophrenia pathology: recent insights and concepts of therapy. Schizophr. Res. 161:1 (2015), 4–18.
8. Bezdudnaya, T., Keller, A., Laterodorsal nucleus of the thalamus: a processor of somatosensory inputs. J. Comp. Neurol. 507:6 (2008), 1979–1989.
9. Bogerts, B., Lieberman, J.A., Ashtari, M., Bilder, R.M., Degreef, G., Lerner, G., Johns, C., Masiar, S., Hippocampus–amygdala volumes and psychopathology in chronic schizophrenia. Biol. Psychiatry 33:4 (1993), 236–246.
10. Brisch, R., Saniotis, A., Wolf, R., Bielau, H., Bernstein, H.G., Steiner, J., Bogerts, B., Braun, K., Jankowski, Z., Kumaratilake, J., Henneberg, M., Gos, T., The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue. Front. Psychiatry, 5, 2014, 47.
11. Busse, S., Busse, M., Schiltz, K., Bielau, H., Gos, T., Brisch, R., Mawrin, C., Schmitt, A., Jordan, W., Muller, U.J., Bernstein, H.G., Bogerts, B., Steiner, J., Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: further evidence for disease course-related immune alterations?. Brain Behav. Immun. 26:8 (2012), 1273–1279.
12. Carmans, S., Hendriks, J.J., Slaets, H., Thewissen, K., Stinissen, P., Rigo, J.M., Hellings, N., Systemic treatment with the inhibitory neurotransmitter gamma-aminobutyric acid aggravates experimental autoimmune encephalomyelitis by affecting proinflammatory immune responses. J. Neuroimmunol. 255:1–2 (2013), 45–53.
13. Curley, A.A., Arion, D., Volk, D.W., Asafu-Adjei, J.K., Sampson, A.R., Fish, K.N., Lewis, D.A., Cortical deficits of glutamic acid decarboxylase 67 expression in schizophrenia: clinical, protein, and cell type-specific features. Am. J. Psychiatry 168:9 (2011), 921–929.
14. Flores, C.E., Mendez, P., Shaping inhibition: activity dependent structural plasticity of GABAergic synapses. Front. Cell. Neurosci., 8, 2014, 327.
15. Gill, K.M., Lodge, D.J., Cook, J.M., Aras, S., Grace, A.A., A novel alpha5GABA(A)R-positive allosteric modulator reverses hyperactivation of the dopamine system in the MAM model of schizophrenia. Neuropsychopharmacology 36:9 (2011), 1903–1911.
16. Glausier, J.R., Fish, K.N., Lewis, D.A., Altered parvalbumin basket cell inputs in the dorsolateral prefrontal cortex of schizophrenia subjects. Mol. Psychiatry 19:1 (2014), 30–36.
17. Glausier, J.R., Kimoto, S., Fish, K.N., Lewis, D.A., Lower glutamic acid decarboxylase 65-kDa isoform messenger RNA and protein levels in the prefrontal cortex in schizoaffective disorder but not schizophrenia. Biol. Psychiatry 77:2 (2015), 167–176.
18. Gonzalez-Burgos, G., Lewis, D.A., GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia. Schizophr. Bull. 34:5 (2008), 944–961.
19. Gos, T., Günther, K., Bielau, H., Dobrowolny, H., Mawrin, C., Trubner, K., Brisch, R., Steiner, J., Bernstein, H.G., Jankowski, Z., Bogerts, B., Suicide and depression in the quantitative analysis of glutamic acid decarboxylase-immunoreactive neuropil. J. Affect. Disord. 113:1–2 (2009), 45–55.
20. Gos, T., Myint, A.M., Schiltz, K., Meyer-Lotz, G., Dobrowolny, H., Busse, S., Muller, U.J., Mawrin, C., Bernstein, H.G., Bogerts, B., Steiner, J., Reduced microglial immunoreactivity for endogenous NMDA receptor agonist quinolinic acid in the hippocampus of schizophrenia patients. Brain Behav. Immun. 41 (2014), 59–64.
21. Gos, T., Steiner, J., Bielau, H., Dobrowolny, H., Günther, K., Mawrin, C., Krzyzanowski, M., Hauser, R., Brisch, R., Bernstein, H.G., Jankowski, Z., Braun, K., Bogerts, B., Differences between unipolar and bipolar I depression in the quantitative analysis of glutamic acid decarboxylase-immunoreactive neuropil. Eur. Arch. Psychiatry Clin. Neurosci. 262:8 (2012), 647–655.
22. Heckers, S., Konradi, C., GABAergic mechanisms of hippocampal hyperactivity in schizophrenia. Schizophr. Res. 167:1–3 (2015), 4–11.
23. Hirayasu, Y., Shenton, M.E., Salisbury, D.F., Dickey, C.C., Fischer, I.A., Mazzoni, P., Kisler, T., Arakaki, H., Kwon, J.S., Anderson, J.E., Yurgelun-Todd, D., Tohen, M., McCarley, R.W., Lower left temporal lobe MRI volumes in patients with first-episode schizophrenia compared with psychotic patients with first-episode affective disorder and normal subjects. Am. J. Psychiatry 155:10 (1998), 1384–1391.
24. Hor, K., Taylor, M., Suicide and schizophrenia: a systematic review of rates and risk factors. J. Psychopharmacol. 24:4 Suppl. (2010), 81–90.
25. Jagasia, R., Steib, K., Englberger, E., Herold, S., Faus-Kessler, T., Saxe, M., Gage, F.H., Song, H., Lie, D.C., GABA-cAMP response element-binding protein signaling regulates maturation and survival of newly generated neurons in the adult hippocampus. J. Neurosci. 29:25 (2009), 7966–7977.
26. Jin, Z., Mendu, S.K., Birnir, B., GABA is an effective immunomodulatory molecule. Amino Acids 45:1 (2013), 87–94.
27. Kegel, M.E., Bhat, M., Skogh, E., Samuelsson, M., Lundberg, K., Dahl, M.L., Sellgren, C., Schwieler, L., Engberg, G., Schuppe-Koistinen, I., Erhardt, S., Imbalanced kynurenine pathway in schizophrenia. Int. J. Tryptophan Res. 7 (2014), 15–22.
28. Kuhn, S.A., van Landeghem, F.K., Zacharias, R., Farber, K., Rappert, A., Pavlovic, S., Hoffmann, A., Nolte, C., Kettenmann, H., Microglia express GABA(B) receptors to modulate interleukin release. Mol. Cell. Neurosci. 25:2 (2004), 312–322.
29. Lee, M., Schwab, C., McGeer, P.L., Astrocytes are GABAergic cells that modulate microglial activity. Glia 59:1 (2011), 152–165.
30. Lewis, D.A., Curley, A.A., Glausier, J.R., Volk, D.W., Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia. Trends Neurosci. 35:1 (2012), 57–67.
31. Liang, K.Y., Zeger, S., Longitudinal data analysis using generalized linear models. Biometrika 73:1 (1986), 13–22.
32. Lin, X., Carroll, R.J., Semiparametric regression for clustered data using generalized estimating equations. J. Am. Stat. Assoc. 96:455 (2001), 1045–1056.
33. Lisman, J.E., Coyle, J.T., Green, R.W., Javitt, D.C., Benes, F.M., Heckers, S., Grace, A.A., Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci. 31:5 (2008), 234–242.
34. van Lutterveld, R., Sommer, I.E., Ford, J.M., The neurophysiology of auditory hallucinations — a historical and contemporary review. Front. Psychiatry, 2, 2011, 28.
35. Mai, J.K., Assheuer, J., Paxinos, G., Atlas of the Human Brain. second ed, 2003, Academic Press, San Diego.
36. Medalla, M., Barbas, H., Specialized prefrontal “auditory fields”: organization of primate prefrontal-temporal pathways. Front. Neurosci., 8, 2014, 77.
37. Mitchell, A.C., Jiang, Y., Peter, C., Akbarian, S., Transcriptional regulation of GAD1 GABA synthesis gene in the prefrontal cortex of subjects with schizophrenia. Schizophr. Res. 167:1–3 (2015), 28–34.
38. Moghaddam, B., Javitt, D., From revolution to evolution: the glutamate hypothesis of schizophrenia and its implication for treatment. Neuropsychopharmacology 37:1 (2012), 4–15.
39. Moyer, C.E., Delevich, K.M., Fish, K.N., Asafu-Adjei, J.K., Sampson, A.R., Dorph-Petersen, K.A., Lewis, D.A., Sweet, R.A., Reduced glutamate decarboxylase 65 protein within primary auditory cortex inhibitory boutons in schizophrenia. Biol. Psychiatry 72:9 (2012), 734–743.
40. Müller, N., Myint, A.M., Krause, D., Weidinger, E., Schwarz, M.J., Anti-inflammatory treatment in schizophrenia. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 42 (2013), 146–153.
41. Myint, A.M., Kim, Y.K., Network beyond IDO in psychiatric disorders: revisiting neurodegeneration hypothesis. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 48 (2014), 304–313.
42. Narr, K.L., Thompson, P.M., Sharma, T., Moussai, J., Blanton, R., Anvar, B., Edris, A., Krupp, R., Rayman, J., Khaledy, M., Toga, A.W., Three-dimensional mapping of temporo-limbic regions and the lateral ventricles in schizophrenia: gender effects. Biol. Psychiatry 50:2 (2001), 84–97.
43. Nenadic, I., Smesny, S., Schlosser, R.G., Sauer, H., Gaser, C., Auditory hallucinations and brain structure in schizophrenia: voxel-based morphometric study. Br. J. Psychiatry 196:5 (2010), 412–413.
44. Pegues, M.P., Rogers, L.J., Amend, D., Vinogradov, S., Deicken, R.F., Anterior hippocampal volume reduction in male patients with schizophrenia. Schizophr. Res. 60:2–3 (2003), 105–115.
45. Perez, S.M., Lodge, D.J., Hippocampal interneuron transplants reverse aberrant dopamine system function and behavior in a rodent model of schizophrenia. Mol. Psychiatry 18:11 (2013), 1193–1198.
46. Rametti, G., Segarra, N., Junque, C., Bargallo, N., Caldu, X., Ibarretxe, N., Bernardo, M., Left posterior hippocampal density reduction using VBM and stereological MRI procedures in schizophrenia. Schizophr. Res. 96:1–3 (2007), 62–71.
47. Rey, M.J., Schulz, P., Costa, C., Dick, P., Tissot, R., Guidelines for the dosage of neuroleptics. I: Chlorpromazine equivalents of orally administered neuroleptics. Int. Clin. Psychopharmacol. 4:2 (1989), 95–104.
48. Sanchez, P.E., Zhu, L., Verret, L., Vossel, K.A., Orr, A.G., Cirrito, J.R., Devidze, N., Ho, K., Yu, G.Q., Palop, J.J., Mucke, L., Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer's disease model. Proc. Natl. Acad. Sci. U. S. A. 109:42 (2012), E2895–E2903.
49. Schmitt, A., Malchow, B., Hasan, A., Falkai, P., The impact of environmental factors in severe psychiatric disorders. Front. Neurosci., 8, 2014, 19.
50. Schobel, S.A., Chaudhury, N.H., Khan, U.A., Paniagua, B., Styner, M.A., Asllani, I., Inbar, B.P., Corcoran, C.M., Lieberman, J.A., Moore, H., Small, S.A., Imaging patients with psychosis and a mouse model establishes a spreading pattern of hippocampal dysfunction and implicates glutamate as a driver. Neuron 78:1 (2013), 81–93.
51. Schobel, S.A., Lewandowski, N.M., Corcoran, C.M., Moore, H., Brown, T., Malaspina, D., Small, S.A., Differential targeting of the CA1 subfield of the hippocampal formation by schizophrenia and related psychotic disorders. Arch. Gen. Psychiatry 66:9 (2009), 938–946.
52. Small, S.A., Schobel, S.A., Buxton, R.B., Witter, M.P., Barnes, C.A., A pathophysiological framework of hippocampal dysfunction in ageing and disease. Nat. Rev. Neurosci. 12:10 (2011), 585–601.
53. Steiner, J., Bernstein, H.G., Bielau, H., Farkas, N., Winter, J., Dobrowolny, H., Brisch, R., Gos, T., Mawrin, C., Myint, A.M., Bogerts, B., S100B-immunopositive glia is elevated in paranoid as compared to residual schizophrenia: a morphometric study. J. Psychiatr. Res. 42:10 (2008), 868–876.
54. Steiner, J., Bogerts, B., Sarnyai, Z., Walter, M., Gos, T., Bernstein, H.G., Myint, A.M., Bridging the gap between the immune and glutamate hypotheses of schizophrenia and major depression: potential role of glial NMDA receptor modulators and impaired blood–brain barrier integrity. World J. Biol. Psychiatry 13:7 (2012), 482–492.
55. Steullet, P., Cabungcal, J.H., Monin, A., Dwir, D., O'Donnell, P., Cuenod, M., Do, K.Q., Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: a “central hub” in schizophrenia pathophysiology?. Schizophr. Res. 176:1 (2016), 41–51.
56. Sweet, R.A., Bergen, S.E., Sun, Z., Marcsisin, M.J., Sampson, A.R., Lewis, D.A., Anatomical evidence of impaired feedforward auditory processing in schizophrenia. Biol. Psychiatry 61:7 (2007), 854–864.
57. Szeszko, P.R., Goldberg, E., Gunduz-Bruce, H., Ashtari, M., Robinson, D., Malhotra, A.K., Lencz, T., Bates, J., Crandall, D.T., Kane, J.M., Bilder, R.M., Smaller anterior hippocampal formation volume in antipsychotic-naive patients with first-episode schizophrenia. Am. J. Psychiatry 160:12 (2003), 2190–2197.
58. Todtenkopf, M.S., Benes, F.M., Distribution of glutamate decarboxylase65 immunoreactive puncta on pyramidal and nonpyramidal neurons in hippocampus of schizophrenic brain. Synapse 29:4 (1998), 323–332.
59. Velakoulis, D., Stuart, G.W., Wood, S.J., Smith, D.J., Brewer, W.J., Desmond, P., Singh, B., Copolov, D., Pantelis, C., Selective bilateral hippocampal volume loss in chronic schizophrenia. Biol. Psychiatry 50:7 (2001), 531–539.
60. Woo, T.U., Whitehead, R.E., Melchitzky, D.S., Lewis, D.A., A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia. Proc. Natl. Acad. Sci. U. S. A. 95:9 (1998), 5341–5346.
61. Yao, J.K., Keshavan, M.S., Antioxidants, redox signaling, and pathophysiology in schizophrenia: an integrative view. Antioxid. Redox Signal. 15:7 (2011), 2011–2035.
62. Zhang, Y., Behrens, M.M., Lisman, J.E., Prolonged exposure to NMDAR antagonist suppresses inhibitory synaptic transmission in prefrontal cortex. J. Neurophysiol. 100:2 (2008), 959–965.
63. Zierhut, K.C., Grassmann, R., Kaufmann, J., Steiner, J., Bogerts, B., Schiltz, K., Hippocampal CA1 deformity is related to symptom severity and antipsychotic dosage in schizophrenia. Brain 136:Pt 3 (2013), 804–814.