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Noradrenergic Pathology in Psychiatric Disorders: Postmortem Studies

Published online by Cambridge University Press:  07 November 2014

Abstract

In this paper, we review research utilizing postmortem brain tissue in order to investigate the potential neuropathology of the noradrenergic system in psychiatri disorders. The postmortem tissue approach to the study of the noradrenergic system has been used primarily in investigations of the biology of suicide and depression. Findings from postmortem studies provide data generally consisten with the hypothesis that a norepinephrine deficiency exist depression, and possibly in the victims of suicide. However postmortem studies do not presently provide irrefutable evidence of noradrenergic neuropathology. Technical shortcomings, issues of reproducibility, and the strengths postmortem research are reviewed. More rigorously performed postmortem research is needed to aid researchers in pinpointing specific neuropathologies associated with psychiatric disease.

Type
Feature Articles
Copyright
Copyright © Cambridge University Press 2001

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References

REFERENCES

1. Prange, AJ Jr., The pharmacology and biochemistry of depression. Dis New Syst. 1964;5:217221.Google Scholar
2. Schildkraut, JJ. The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry. 1965;122:509522.Google Scholar
3. Koslow, SH, Maas, JW, Bowden, CL et al. , CSF and urinary biogenic amines and metabolites in depression and mania: a controlled, univariate analysis. Arch Gen Psychiatry. 1983;40:9991010.Google Scholar
4. Redmond, DE, Katz, MM, Maas, JW et al. , Cerebrospinal fluid amine metabolites: relationships with behavioral measurements in depressed, manic, and healthy control subjects. Arch Gen Psychiatry. 1986;43:938947.CrossRefGoogle ScholarPubMed
5. Beckmann, H, Goodwin, FK. Urinary MHPG in subgroups of depressed patients and normal controls. Neuropsychobiology. 1980;6:91100.CrossRefGoogle ScholarPubMed
6. Roy, A, Pickar, D, Linnoila, M, Potter, WZ. Plasma norepinephrine level in affective disorders: relationship to melancholia. Arch Gen Psychiatry. 1985;42:11811185.Google Scholar
7. Veith, R, Lewis, N, Linares, O et al. , Sympathetic nervous system activity in major depression: basal and desipramine-induced alterations in plasma norepinephrine kinetics. Arch Gen Psychiatry. 1994;51:411422.Google Scholar
8. Charney, DS. Monoamine dysfunction and the pathophysiology and treatment of depression. J Clin Psychiatry. 1998;59(Suppl 14):1114.Google Scholar
9. Salomon, R, Miller, HL, Krystal, JH et al. , Lack of behavioral effects of monoamine depletion in healthy subjects. Biol Psychiatry. 1997;41:5864.Google Scholar
10. Delgado, PL. Depression: the case for a monoamine deficiency. J Clin Psychiatry. 2000;61(Suppl 6):711.Google Scholar
11. Berman, RM, Narasimhan, M, Miller, H et al. , Transient depressive relapse induced by catecholamine depletion. Arch Gen Psychiatry. 1999;56:395403.Google Scholar
12. Hornykiewicz, O. Brain noradrenaline and schizophrenia. In: JM, Van Ree, SW, Matthysse, eds. Progress in Brain Research. Vienna: Elsevier Science Publisher; 1986:2939.Google Scholar
13. Weinberger, DR. Schizophrenia and the frontal lobe. TINS. 1988;11:367370.Google ScholarPubMed
14. Archer, T, Ogren, SO, Johansson, G, Ross, SB. DSP4-induced two-way active avoidance impairment in rats: involvement of central and not peripheral noradrenaline depletion. Psychopharmacology. 1982;76:303309.Google Scholar
15. Mason, ST. Noradrenaline in the brain: progress in theories of behavioural function. Prog Neurobiol. 1981;16:263303.Google Scholar
16. Plaznik, A, Pucilowski, O, Kostowski, W et al. , Rotational behavior produced by unilateral ventral noradrenergic bundle lesions: evidence for a noradrenergic-dopaminergic interaction in the brain. Pharmacol Biochem Behav. 1982;17:619622.Google Scholar
17. Lake, CR, Steinberg, DE, van Kammen, DP et al. , Schizophrenia: elevated cerebrospinal fluid norepinephrine. Science. 1980;207:331333.Google Scholar
18. Sternberg, DE, Van Kammen, DP, Lake, CR et al. , The effect of pimozide on CSF norepinephrine in schizophrenia. Am J Psychiatry. 1981;138:10451050.Google ScholarPubMed
19. Van Kammen, DP, Antelman, S. Impaired noradrenergic transmission in schizophrenia? [Review]. Life Sci. 1984;34:14031413.Google Scholar
20. Rich, CL, Young, D, Fowler, RC. San Diego suicide study. Arch Gen Psychiatry. 1986;43:577582.Google Scholar
21. Stockmeier, CA, Jurjus, G. Monoamine receptors in postmortem brain tissue in suicide. In: Agam, G, RH, Belmaker, Everall, I, eds. The Postmortem Brain in Psychiatric Research. Kluwer Academic Publishers; Dortrecht, the Netherlands; 2001: in press.Google Scholar
22. De Paermentier, F, Mauger, JM, Lowther, S et al. , Brain alpha-adrenoceptors in depressed suicides. Brain Res. 1997;757:6068.CrossRefGoogle ScholarPubMed
23. Arango, V, Ernsberger, P, Syed, AF, Mann, JJ. Quantitative autoradiography of a1 and a2 adrenergic receptors in the cerebral cortex of controls and suicide vietims. Brain Res. 1993;630:271282.Google Scholar
24. Gross-Isseroff, R, Dillon, KA, Fieldust, SJ, Biegon, A. Autoradiographic analysis of alpha 1-noradrenergic receptors in the human brain postmortem. Effect of suicide [published erratum appears in Arch Gen Psychiatry 1991 Sep;48(9):862]. Arch Gen Psychiatry: 1990;47:10491053.Google Scholar
25. Crow, TJ, Cross, AJ, Cooper, SJ et al. , Neurotransmitter receptors and monoamine metabolites in the brains of patients with Alzheimer-type dementia and depression, and suicides. Neuropharmacology. 1984;23:15611569.CrossRefGoogle ScholarPubMed
26. Klimek, V, Rajkowska, G, Luker, SN et al. , Brain noradrenergic receptors in major depression and schizophrenia. Neuropsychopharmacology. 1999;21:6981.CrossRefGoogle ScholarPubMed
27. Ferrier, IN, McKeith, IG, Cross, AJ et al. , Postmortem neurochemical studies in depression. Ann N Y Acad Sci. 1986;487:128142.Google Scholar
28. Meana, JJ, Garcia-Sevilla, JA. Increased a2-adrenoceptor density in the frontal cortex of depressed suicide victims. J Neural Transm. 1987;70:377381.Google Scholar
29. Meana, JJ, Barturen, F, Garcia-Sevilla, JA. Alpha2-adrenoceptors in the brain of suicide victims: increased receptor density associated with major depression. Biol Psychiatry. 1992;31:471490.Google Scholar
30. Sirota, P. Is schizophrenia an autoimmune disease. Isr J Med Sci. 1990;26:694697.Google Scholar
31. Joyce, JN, Lexow, N, Jin Kim, S et al. , Distribution of beta-adrenergic receptor subtypes in human post-mortem brain: Alterations in limbic regions of schizophrenics. Synapse. 1992;10:228246.Google Scholar
32. Bennett, JP, Enna, SJ, Bylund, DB et al. , Neurotransmitter receptors in frontal cortex of schizophrenics. Arch Gen Psychiatry. 1979;36:927934.Google Scholar
33. De Paermentier, F, Cheetham, SC, Crompton, MR et al. , Brain beta-adrenoceptor binding sites in antidepressant-free depressed suicide victims. Brain Res. 1990;525:7177.Google Scholar
34. Mann, JJ, Stanley, M, McBride, PA, McEwen, BS. Increased serotonin2 and b-adrenergic receptor binding in the frontal cortices of suicide victims. Arch Gen Psychiatry. 1986;43:954959.Google Scholar
35. Arango, V, Ernsberger, P, Marzuk, PM et al. , Autoradiographic demonstration of increased serotonin 5-HT2 and B-adrenergic receptor binding sites in the brain of suicide victims. Arch Gen Psychiatry. 1990;47:10381047.Google Scholar
36. Biegon, A, Israeli, M. Regionally selective increases in b-adrenergic receptor density in the brains of suicide victims. Brain Res. 1988;442:199203.Google Scholar
37. Gross-Isseroff, R, Israeli, M, Biegon, A. Autoradiographic analysis of [3H] desmethylimipramine binding in the human brain postmortem. Brain Res. 1988;456:120126.Google Scholar
38. Arora, RC, Meltzer, HY. Laterality and 3H-imipramine binding: studies in the frontal cortex of normal controls and suicide victims. Biol Psychiatry. 1991;29:10161022.Google Scholar
39. Stanley, M, Virgilio, J, Gershon, S. Tritiated imipramine binding sites are decreased in the frontal cortex of suicides. Science. 1982;216:13371339.CrossRefGoogle ScholarPubMed
40. Grote, SS, Moses, SG, Robins, E et al. , A study of selected catecholamine metabolizing enzymes: a comparison of depressive suicides and alcoholic suicides with controls. J Neurochem. 1974;23:791802.Google Scholar
41. Mann, J. J. and Stanley, M.postmortem monoamine oxidase enzyme kinetics in the frontal cortex of suicide victims and controls. Acta Psychiatr Scand. 1984;69:135139.Google Scholar
42. Maeztu, AI, Ballesteros, J, Callado, LF et al. , The density of monoamine oxidase B sites is not altered in the postmortem brain of alcoholics. Alcohol Clin Exp Res. 1997;21:14791483.Google Scholar
43. Gottfries, CG, Oreland, L, Wiberg, A, Winblad, B. Lowered monoamine oxidase activity in brains from alcoholic suicides. J Neurochem. 1975;25:667673.CrossRefGoogle ScholarPubMed
44. Callado, LF, Meana, JJ, Grijalba, B et al. , Selective increase of a2A-adrenoceptor agonist binding sites in brains of depressed suicide victims. J Neurochem. 1998;70:11141123.Google Scholar
45. Garcia, S, Escriba, PV, Ozaita, A et al. , Up-regulation of immunolabeled alpha2Aadrenoceptors, Gi coupling proteins, and regulatory receptor kinases in the prefrontal cortex of depressed suicides. J Neurochem. 1999;72:282291.Google Scholar
46. Ordway, GA, Widdowson, PS, Smith, KS, Halaris, A. Agonist binding to a2-adrenoceptors is elevated in the locus coeruleus from victims of suicide. J Neurochem. 1994;63:617624.Google Scholar
47. Ordway, GA, Schenck, JE, Dilley, GE et al. , Increased p-[125I]iodoclonidine binding to a2-adrenoceptors in the locus coeruleus in major depression. Soc Neurosci Abs. 1999;25:2139Google Scholar
48. Klimek, V, Stockmeier, CA, Overholser, JC et al. , Reduced levels of norepinephrine transporters in the locus coeruleus in major depression. J Neurosci. 1997;17:84518458.Google Scholar
49. Ordway, GA, Farley, IJ, Dilley, GE et al. , Quantitative distribution of monoamine oxidase A in brainstem monoamine nuclei is normal in major depression. Brain Res. 1999;847:7179.CrossRefGoogle ScholarPubMed
50. Ordway, GA, Smith, KS, Haycock, JW. Elevated tyrosine hydroxylase in the locus coeruleus of suicide victims. J Neurochem. 1994;62:680685.CrossRefGoogle ScholarPubMed
51. Zhu, M-Y, Klimek, V, Dilley, GE et al. , Elevated levels of tyrosine hydroxylase in the locus coeruleus in major depression. Biol Psychiatry. 1999;46:12751286.Google Scholar
52. Biegon, A, Fieldust, S. Reduced tyrosine hydroxylase immunoreactivity in locus coeruleus of suicide victims. Synapse. 1992;10:7982.CrossRefGoogle ScholarPubMed
53. Baumann, B, Danos, P, Diekmann, S et al. , Tyrosine hydroxylase immunoreactivity in the locus coeruleus is reduced in depressed non-suicidal patients but normal in depressed suicide patients. Eur Arch Psychiatry Clin Neurosci. 1999;249:212219.Google Scholar
54. Arango, V, Undenvood, MD, Mann, JJ. Fewer pigmented locus coeruleus neurons in suicide victims: preliminary results. Biol Psychiatry. 1996;39:112120.Google Scholar
55. Danysz, W, Kostowski, W, Hauptmann, M. Evidence for the locus coeruleus involvement in desipramine action in animal models of depression. Pol J Pharmacol Pharm. 1985;7:855864.Google Scholar
56. Wolfe, BB, Harden, TK, Sporn, JR, Molinoff, PB. Presynaptic modulation of beta adrenergic receptors in rat cerebral cortex after treatment with antidepressants. J Pharmacol Exp Ther. 1978;207:446457.Google Scholar
57. Biegon, A, Rainbow, TC. Localization and characterization of [3H]desmethylimipramine binding sites in rat brain by quantitative autoradiography. J Neurosci. 1983;3:10691076.Google Scholar
58. Richards, JG, Saura, J, Ulrich, J, DaPrada, M. Molecular neuroanatomy of monoamine oxidases in human brainstem. Psychopharmacology. 1992;106 (Suppl):S2123.Google Scholar
59. Cortes, R, Soriano, E, Pazos, A et al. , Autoradiography of antidepressant binding sites in the human brain: localization using [3H]imipramine and [3H]paroxetine. Neuroscience. 1988;27:473496.Google Scholar
60. Hrdina, PD, Foy, B, Hepner, A, Summers, RJ. Antidepressant binding sites in the brain: autoradiographic comparison of [3H]paroxetine and [3H]imipramine localization and relationship to serotonin transporter. J Pharmacol Exp Ther. 1990;52:410418.Google Scholar
61. Kovachich, GB, Frazer, A, Aronson, CE. Effect of chronic administration of antidepressants on alpha 2-adrenoceptors in the locus coeruleus and its projection fields in rat brain determined by quantitative autoradiography. Neuropsychopharmacology. 1993;8:5765.Google Scholar
62. Melia, KR, Rasmussen, K, Terwilliger, RZ et al. , Coordinate regulation of the cyclic AMP system with firing rate and expression of tyrosine hydroxylase in the rat locus coeruleus: effects of chronic stress and drug treatments. J Neurochem. 1992;58:494502.CrossRefGoogle ScholarPubMed
63. Weiss, JM, Goodman, PA, Losito, BG et al. , Behavioral depression produced by an uncontrollable stressor: Relationship to norepinephrine, dopamine, and serotonin levels in various regions of rat brain. Brain Res Rev. 1981;3:167205.Google Scholar
64. U'Prichard, DC, Bechtel, WD, Rouot, BM, Snyder, SH. Multiple apparent alphanoradrenergic receptor binding sites in rat brain: effect of 6-hydroxydopamine. Mol Pharmacol. 1979;16:4760.Google Scholar
65. Gross, G, Gothert, M, Glapa, U et al. , Lesioning of serotoninergic and noradrenergic nerve fiber's of the rat brain does not decrease binding of 3H-clonidine and 3H-rauwolscine to cortical membranes. Naunyn-Schmiedeherg's Arch Pharmacol. 1985;328:229235.Google Scholar
66. Cubells, JF, Kim, KS, Baker, H et al. , Differential in vivo regulation of mRNA encoding the norepinephrine transporter and tyrosine hydroxylase in rat adrenal medulla and locus coeruleus. J Neurochem. 1995;65:502509.Google Scholar
67. Lee, C-M, Javitch, JA, Snyder, SH. Recognition sites for norepinephrine uptake: regulation by neurotransmitter. Science. 1983;220:626629.Google Scholar
68. Johnson, EW, Wolfe, BB, Molinoff, PB. Regulation of subtypes of B-adrenergic receptors in rat brain following treatment with 6-hydroxydopamine. J Neurosci. 1989;9:22972305.Google Scholar
69. Ordway, GA, Gambarana, C, Frazer, A. Quantitative autoradiography of central beta adrenoceptor subtypes: comparison of the effects of chronic treatment with desipramine or centrally administered l-isoproterenol. J Pharmacol Exp Ther. 1988;247:379389.Google Scholar
70. Ordway, GA, Klimek, V, Mann, JJ. Neurocircuitry of mood disorders. In: Anonymous Psychopharmacology: The Fifth Generation of Progress. 2001: in press.Google Scholar