Studies in the Human Frontal Cortex: Evidence for Changes in Neurochemical Markers in Schizophrenia and Bipolar Disorder

  • Brian Dean
Part of the Neurobiological Foundation of Aberrant Behaviors book series (NFAB, volume 4)

Abstract

Commonality of treatments in schizophrenia and bipolar disorder suggest that there may be a single pathology driving some of the symptoms of these illnesses. To test this hypothesis, the literature on the changes in the molecular neuroanatomy of postmortem brain tissue from subjects with schizophrenia and bipolar disorder has been reviewed to attempt to identify a common neurobiology. Such studies provide evidence to suggest that changes in the serotonergic system of the frontal cortex may be such a common factor. However, currently available data does not support the argument that the same changes in the serotonergic systems of the frontal cortex are present in schizophrenia and bipolar disorder. By contrast, such data would suggest that targeting receptor-G-protein interactions might be therapeutically beneficial in both illnesses.

Keywords

Bipolar Disorder Frontal Cortex Serotonin Receptor Serotonin Transporter Serotonergic System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Akil M, Pierri JN, Whitehead RE, Edgar CL, Mohila C, Sampson AR, and Lewis DA. Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects. A J Psychiatry 1999; 156: 1580–1589.Google Scholar
  2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (Forth edition). American Psychiatric Association, Washington, D.C., 1994.Google Scholar
  3. Andrews G, Hall W, Goldstein G, Lapsley H, Bartels R, and Silove D. The economic costs of schizophrenia. Implications for public policy. Arch Gen Psychiatry 1985; 42: 537–543.PubMedCrossRefGoogle Scholar
  4. Arora RC and Meltzer HY. Serotonin2 (5-HT2) receptor binding in the frontal cortex of schizophrenic patients. J Neural Transm Gen Sect 1991; 85: 19–29.PubMedCrossRefGoogle Scholar
  5. Avissar S, Schreiber G, Aulakh CS, Wozniak KM, and Murphy DL. Carbamazepine and electroconvulsive shock attenuate beta-adrenoceptor and muscarinic cholinoceptor coupling to G proteins in rat cortex. Eur J Pharmacol 1990; 189: 99–103.PubMedCrossRefGoogle Scholar
  6. Bennett JP, Enna SJ, Bylund DB, Gillin JC, Wyatt RJ, and Snyder SH. Neurotransmitter receptors in frontal cortex of schizophrenics. Arch Gen Psychiatry 1979; 36: 927–934.PubMedCrossRefGoogle Scholar
  7. Burnet PW, Eastwood SL, and Harrison PJ. 5-HT1A and 5-HT2A receptor mRNA and binding site densities are differentially altered in schizophrenia. Neuropsychopharmacology 1996; 15: 442–455.PubMedCrossRefGoogle Scholar
  8. Calabrese JR, Bowden V, and Woyshville MJ. Lithium and the anticonvilsants in bipolar disorder. In: Bloom FE and Kupfer DJ, (eds). Psychopharmacology: The Fourth Generation of Progress. Raven Press,New York, 1995; pp 1099–1111.Google Scholar
  9. Dean B. Signal transmission, rather than reception, is the underlying neurochemical abnormality in schizophrenia. Aust N Z J Psychiatry 2000; 34: 560–569.PubMedCrossRefGoogle Scholar
  10. Dean B and Hayes W. Decreased frontal cortical serotonin2A receptors in schizophrenia. Schizophr Res 1996; 21: 133–139.PubMedCrossRefGoogle Scholar
  11. Dean B, Hayes W, Hill C, and Copolov D. Decreased serotonin2A receptors in Brodmann’s area 9 from schizophrenic subjects. A pathological or pharmacological phenomenon? Mol Chem Neuropathol 1998; 34: 133–145.PubMedCrossRefGoogle Scholar
  12. Dean B, Hussain T, Hayes W, Scan E, Kitsoulis S, Hill C, Opeskin K, and Copolov DL. Changes in serotonin2A and GABA(A) receptors in schizophrenia: studies on the human dorsolateral prefrontal cortex. J Neurochem 1999a; 72: 1593–1599.PubMedCrossRefGoogle Scholar
  13. Dean B, Opeskin K, Pavey G, Naylor L, Hill C, Keks N, and Copolov DL. [3H]paroxetine binding is altered in the hippocampus but not the frontal cortex or caudate nucleus from subjects with schizophrenia. J Neurochem 1995; 64: 1197–1202.PubMedCrossRefGoogle Scholar
  14. Dean B, Pavey G, McLeod M, Opeskin K, Keks N, and Copolov D. Evidence for an abnormality in the assembly of the GABAA receptor in the prefrontal cortex of subjects with bipolar disorder. J Affect Dis 2000; (In press).Google Scholar
  15. Dean B, Tomaskovic-Crook E, Opeskin K, Keks N, and Copolov D. No change in the density of the serotoninlA receptor, the serotonin4 receptor or the serotonin transporter in the dorsolateral prefrontal cortex from subjects with schizophrenia. Neurochem Int 1999b; 34: 109–115.PubMedCrossRefGoogle Scholar
  16. Friedman E and Wang HY. Receptor-mediated activation of G proteins is increased in postmortem brains of bipolar affective disorder subjects. J Neurochem 1996; 67: 1145 1152.Google Scholar
  17. Fuster JM. The Prefrontal Cortex: Anatomy, Physiology and Neuropsychology of the Frontal Lobe. Raven Press, New York, 1989.Google Scholar
  18. Gerner RH, Post RM, and Bunney WE, Jr. A dopaminergic mechanism in mania. Am J Psychiatry 1976; 133: 1177–1180.PubMedGoogle Scholar
  19. Gurevich EV and Joyce JN. Alterations in the cortical serotonergic system in schizophrenia: A postmortem study. Biol Psychiatry 1997; 42: 529–545.PubMedCrossRefGoogle Scholar
  20. Hashimoto T, Kitamura N, Kajimoto Y, Shirai Y, Shirakawa O, Mita T, Nishino N, and Tanaka C. Differential changes in serotonin 5-HT1A and 5-HT2 receptor binding in patients with chronic schizophrenia. Psychopharmacology (Berl) 1993; 112: S35 - S39.CrossRefGoogle Scholar
  21. Hashimoto T, Nishino N, Nakai H, and Tanaka C. Increase in serotonin 5-HT IA receptors in prefrontal and temporal cortices of brains from patients with chronic schizophrenia. Life Sci 1991; 48: 355–363.PubMedCrossRefGoogle Scholar
  22. Hitri A, Casanova MF, Kleinman JE, Weinberger DR, and Wyatt RJ. Age-related changes in [3H]GBR 12935 binding site density in the prefrontal cortex of controls and schizophrenics. Biol Psychiatry 1995; 37: 175–182.PubMedCrossRefGoogle Scholar
  23. Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, and Humphrey PP. International Union of Pharmacology classification of receptors for 5hydroxytryptamine (Serotonin). Pharmacol Rev 1994; 46: 157–203.PubMedGoogle Scholar
  24. Huttunen M. The evolution of the serotonin-dopamine antagonist concept. J Clin Psychopharmacol 1995;1, Suppl 15: 4S - 10S.Google Scholar
  25. Jope RS, Song L, Li PP, Young LT, Kish SJ, Pacheco MA, and Warsh JJ. The phosphoinositide signal transduction system is impaired in bipolar affective disorder brain. J Neurochem 1996; 66: 2402–2409.PubMedCrossRefGoogle Scholar
  26. Joyce JN, Shane A, Lexow N, Winokur A, Casanova MF, and Kleinman JE. Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenics. Neuropsychopharmacology 1993; 8: 315–336.PubMedGoogle Scholar
  27. Keller MB and Baker LA. Bipolar disorder: epidemiology, course, diagnosis, and treatment. Bull Menninger Clin 1991; 55: 172–181.PubMedGoogle Scholar
  28. Knable MB, Hyde TM, Murray AM, Herman MM, and Kleinman JE. A postmortem study of frontal cortical dopamine D1 receptors in schizophrenics, psychiatric controls, and normal controls. Biol Psychiatry 1996; 40: 1191–1199.PubMedCrossRefGoogle Scholar
  29. Laruelle M, Abi-Dargham A, Casanova MF, Toti R, Weinberger DR, and Kleinman JE. Selective abnormalities of prefrontal serotonergic receptors in schizophrenia: A postmortem study. Arch Gen Psychiatry 1993; 50: 810–818.PubMedCrossRefGoogle Scholar
  30. Leake A, Fairbairn AF, McKeith IG, and Ferrier IN. Studies on the serotonin uptake binding site in major depressive disorder and control postmortem brain: neurochemical and clinical correlates. Psychiatry Res 1991; 39: 155–165.PubMedCrossRefGoogle Scholar
  31. Meador-Woodruff JH, Haroutunian V, Powchik P, Davidson M, Davis KL, and Watson SJ. Dopamine receptor transcript expression in striatum and prefrontal and occipital cortex. Focal abnormalities in orbitofrontal cortex in schizophrenia. Arch Gen Psychiatry 1997; 54: 1089–1095.PubMedCrossRefGoogle Scholar
  32. Meltzer HY. Biological studies in schizophrenia. Schizophr Bull 1987; 13: 77–107.PubMedCrossRefGoogle Scholar
  33. Mita T, Hanada S, Nishino N, Kuno T, Nakai H, Yamadori Y, and Tanaka C. Decreased serotonin S2 and increased dopamine D2 receptors in chronic schizophrenics. Biol Psychiatry 1986; 21: 1407–1414.PubMedCrossRefGoogle Scholar
  34. Mu!crone J and Kerwin RW. No difference in the expression of the D4 gene in postmortem frontal cortex from controls and schizophrenics. Neurosci Lett 1996; 219: 163–166.PubMedCrossRefGoogle Scholar
  35. O’Donnell T, Rotzinger S, Nakashima TT, Hanstock CC, Ulrich M, and Silverstone PH. Chronic lithium and sodium valproate both decrease the concentration of myo-inositol and increase the concentration of inositol monophosphates in rat brain. Brain Res 2000; 880: 84–91.PubMedCrossRefGoogle Scholar
  36. Rahman S, Li PP, Young LT, Kofman O, Kish SJ, and Warsh JJ. Reduced [3H]cyclic AMP binding in postmortem brain from subjects with bipolar affective disorder. J Neurochem 1997; 68: 297–304.PubMedCrossRefGoogle Scholar
  37. Scott J, Stanton B, Garland A, and Ferrier IN. Cognitive vulnerability in patients with bipolar disorder. Psychol Med 2000; 30: 467–472.PubMedCrossRefGoogle Scholar
  38. Shimon H, Agam G, Belmaker RH, Hyde TM, and Kleinman JE. Reduced frontal cortex inositol levels in postmortem brain of suicide victims and patients with bipolar disorder. Am J Psychiatry 1997; 154: 1148–1150.PubMedGoogle Scholar
  39. Simpson MDC, Lubman DI, Slater P, and Deakin JFW. Autoradiography with [3H]8-OHDPAT reveals increases in 5-HT1A receptors in ventral prefrontal cortex in schizophrenia. Biol Psychiatry 1996; 39: 919–928.PubMedCrossRefGoogle Scholar
  40. Spleiss O, van Calker D, Scharer L, Adamovic K, Berger M, and Gebicke-Haerter PJ. Abnormal G protein alpha(s)–and alpha(i2)-subunit mRNA expression in bipolar affective disorder. Mol Psychiatry 1998; 3: 512–520.PubMedCrossRefGoogle Scholar
  41. Stefanis NC, Bresnick JN, Kerwin RW, Schofield WN, and McAllister G. Elevation of D4 dopamine receptor mRNA in postmortem schizophrenic brain. Brain Res Mol Brain Res 1998; 53: 112–119.PubMedCrossRefGoogle Scholar
  42. Stevens AA, Goldman-Rakic PS, Gore JC, Fulbright RK, and Wexler BE. Cortical dysfunction in schizophrenia during auditory word and tone working memory demonstrated by functional magnetic resonance imaging. Arch Gen Psychiatry 1998; 55: 1097–1103.PubMedCrossRefGoogle Scholar
  43. Stevens JR. Anatomy of schizophrenia revisited. Schizophr Bull 1997; 23: 373–383.PubMedCrossRefGoogle Scholar
  44. Sumiyoshi T, Stockmeier CA, Overholser JC, Dilley GE, and Meltzer HY. SerotoninlA. receptors are increased in postmortem prefrontal cortex in schizophrenia. Brain Res 1996; 708: 209–214.PubMedCrossRefGoogle Scholar
  45. Vawter MP, Freed WJ, and Kleinman JE. Neuropathology of bipolar disorder. Biol Psychiatry 2000; 48: 486–504.PubMedCrossRefGoogle Scholar
  46. Wirshing WC, Marder SR, Van Putten T, and Ames D. Acute treatment of schizophrenia. In: Bloom FE and Kupfer DJ, (eds). Psychopharmacology: The Fourth Generation of Progress. Raven Press, New York, 1995; pp 1259–1275.Google Scholar
  47. Young LT, Asghari V, Li PP, Kish SJ, Fahnestock M, and Warsh JJ. Stimulatory G-protein alpha-subunit mRNA levels are not increased in autopsied cerebral cortex from patients with bipolar disorder. Brain Res Mol Brain Res 1996, 42: 45–50.PubMedCrossRefGoogle Scholar
  48. Young LT, Li PP, Kish SJ, Siu KP, and Warsh JJ. Postmortem cerebral cortex Gs alpha- subunit levels are elevated in bipolar affective disorder. Brain Res 1991; 553: 323–326.PubMedCrossRefGoogle Scholar
  49. Young LT, Warsh JJ, Kish SJ, Shannak K, and Hornykeiwicz O. Reduced brain 5-HT and elevated NE turnover and metabolites in bipolar affective disorder. Biol Psychiatry 1994; 35: 121–127.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Brian Dean

There are no affiliations available

Personalised recommendations