Molecular and Chemical Neuropathology

, Volume 12, Issue 2, pp 99–119

Huntington’s disease as a model for mood disorders

Clues from neuropathology and neurochemistry
  • Carol Efron Peyser
  • Susan E. Folstein
Article

Abstract

Huntington’s disease (HD) is an inherited neuropsychiatric degenerative process characterized by movement disorder, dementia, and, often, affective disorder (AfD) (seen in 38% of patients). Depression in HD is not just an understandable reaction to fatal illness: 10% of HD patients develop mania; AfD can occur 20 yr before neurological signs; and mood disorders are not randomly distributed, but occur in a subset of HD families. This evidence suggests that AfD in HD relates to brain pathophysiology. With its clear neuropathology, HD is proposed as one model for biological underpinnings of idiopathic AfD. There is striking atrophy and neuronal loss in HD neostriatum, particularly caudate. Caudate has rich connections to the limbic system. It is hypothesized that AfD in HD relates to dysfunction of the part of the neostriatum damaged earliest, dorsal medial caudate. Preliminary studies on neuropathological differences between HD patients with and without AfD are discussed. HD neurochemistry is reviewed, emphasizing the excitotoxin hypothesis, which involves dysfunction of the glutamate neurotransmitter system in HD (especially the NMDA receptor, which contains a channel with a phencyclidine (PCP) binding site). Based on the HD model, it is suggested that the glutamate system (particularly NMDA receptors) be examined in idiopathic AfD.

Index Entries

Huntington’s disease affective disorder excitoxin hypothesis glutamate neurotransmitter system 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aronin, N., Difiglia, M., Graveland, G. A., et al. (1984) Localization of immunoreactive enkaphalins in GABA synthesizing neurons of the rat neostriatum.Brain Res. 300, 376–380.PubMedCrossRefGoogle Scholar
  2. Aronin, N., Cooper, P. E., Lorenz, I. J., et al. Somatostatin is increased in the basal ganglia in Huntington disease. (1983)Ann. Neurol. 13, 519–526.PubMedCrossRefGoogle Scholar
  3. Beal, M. F. and Martin, J. B. (1986) Neuropeptides in neurological disease.Ann. Neurol. 20, 547–565.PubMedCrossRefGoogle Scholar
  4. Benson, D. F. (1982) The treatable dementias, inPsychiatric Aspects of Neurological Disease, vol. II (Benson D. F. and Blumer D., eds.), Grune and Stratton, NY pp. 123–148.Google Scholar
  5. Berger, M., Sperk, G., and Hornykiewicz, O. (1982) Serotonergic denervation partially protects rat striatum from kainic acid toxicity.Nature 299, 254–256.PubMedCrossRefGoogle Scholar
  6. Bernheimer, H. and Hornykiewicz, O. (1973) Brain amines in Huntington’s chorea.Adv. Neurol. 1, 525–531.Google Scholar
  7. Bird, E. D. (1979) Huntington’s chorea,Nuerotransmitter Systems and their Clinical Disorders. (Legg N. J., ed.), Academic, London, pp. 143–150.Google Scholar
  8. Bird, E. D. (1980) Chemical pathology of Huntington’s disease.Annu. Rev. Pharmacol. Toxicol. 20, 533–551.PubMedCrossRefGoogle Scholar
  9. Bird, E. D. and Iversen, L. L. (1974) Huntington’s chorea: Postmortem measurements of glutamic acid decarboxylase, choline acetyl-transferase and dopamine in basal ganglia.Brain 97, 457–472.PubMedCrossRefGoogle Scholar
  10. Bird, E. D., MacKay, A. V. P., Rayner, C. N., and Iversen, L. L. (1973) Reduced glutamic-acid-decarboxylase activity of postmortem brain in Huntington’s chorea.Lancet 1, 1090–1092.PubMedCrossRefGoogle Scholar
  11. Bruyn, G. W. (1968) Huntington’s chorea. Historical, clinical and laboratory synopsis, inHandbook of Clinical Neurology (Vinken P. J. and Bruyn G. W., eds.), North-Holland, Amsterdam, pp. 298–378.Google Scholar
  12. Bruyn, G. W., Bots, G. Th. A. M., and Dom, R. (1979) Huntington’s chorea: Current neuropathological status, inAdvances in Neurology (Chase T. N., Wexler, N. S. and Barbeau, A., eds.) vol. 23, Raven, New York pp. 83–93.Google Scholar
  13. Byers, R. K., Gilles, F. H., and Fung, C. (1973) Huntington’s disease in children: Neuropathologic study of four cases.Neurology 23, 561–569.PubMedGoogle Scholar
  14. Caine, E. D. and Shoulson, I. (1983) Psychiatric syndromes in Huntington’s disease.Am. J. Psychiatry 140, 728–733.PubMedGoogle Scholar
  15. Choi, D. W. (1988) Glutamate neurotoxicity and diseases of the nervous system.Neuron 1, 623–634.PubMedCrossRefGoogle Scholar
  16. Coyle, J. T. and Schwarcz, R. (1976) Lesions of striatal neurons with kainic acid provides a model for Huntington’s chorea.Nature 263, 244–246.PubMedCrossRefGoogle Scholar
  17. Cross, A. J., Slater, P., and Reynolds, G. P. (1986) Reduced high-affinity glutamate uptake sites in the brains of patients with Huntington’s disease.Neurosci. Lett. 67, 199–202.CrossRefGoogle Scholar
  18. Crow, T. W. (1982) The biology of schizophrenia.Experientia 38, 1275.PubMedCrossRefGoogle Scholar
  19. Dawbarn, D., De Quidt, M. E., and Emson, P. C. (1985) Survival of basal ganglia neuropeptide Y-somatostatin neurons in Huntington’s disease.Brain Res. 340, 251–260.PubMedCrossRefGoogle Scholar
  20. De La Monte, S. M., Vonsattel, J-P., and Richardson, E. P. (1988) Morphometric demonstration of atrophic changes in the cerebral cortex, white matter and neostriatum in Huntington’s disease.J. Neuropathol. Exp. Neurol. 47, 516–525.PubMedCrossRefGoogle Scholar
  21. DeFelipe, M. C., DeCedallos, N. L., Gil, C., and Fuentes, J. A. (1985) Chronic antidepressant treatment increases enkephalin levels in nucleus accumbens and striatum of the rat.Eur. J. Pharmacol. 112, 119–122.CrossRefGoogle Scholar
  22. Dening, T. R. and Berrids, G. E. (1989) Wilson’s disease: Psychiatric symptoms in 195 patients.Arch. Gen. Psych. 46, 1126–1134.Google Scholar
  23. Difiglia, M., Aronin, N. and Martin, J. B. (1982) Light and electron microscopic localizations of immunoreactive leu-enkephalin in the monkey basal gangliaJ. Neurosci. 2, 303–320.PubMedGoogle Scholar
  24. Dom, R. (1976)Neostriatal and Thalamic Interneurons. Their Role in the Pathophysiology of Huntington’s Chorea, Parkinson’s Disease and Catatonic Schizophrenia (Acco, Leuven).Google Scholar
  25. Dom, R., Baro, F. and Bruchner, J. M. (1973) A cytometric study of the putamen in different types of Huntington’s chorea, inHuntington’s Chorea, 1872–1972 (Barbeau, A., Chase, T. N., and Paulson, G. W., eds.), Raven, New York pp. 369–385.Google Scholar
  26. Dom, R., Malfroid, M., and Baro, F. (1976b) Neuropathology of Huntington’s chorea: Cytometric studies of the ventrobasal complex of the thalamus.Neurology 26, 64–68.PubMedGoogle Scholar
  27. Emson, P. C., Arregui, A., Clement-Jones, V., Sandberg, B. E. B., and Rossor, M. (1980) Regional distribution of methionine-enkephalin and substance-P like immunoreactivity in normal brain and in Huntington’s disease.Brain Res. 198, 497–500.PubMedCrossRefGoogle Scholar
  28. Enna, S. J. (1981) Neuropharmacological and clinical aspects of gamma-aminobutyric acid (GABA), inNeuropharmacology of Central Nervous System and Behavioral Disorders (Palmer, G., ed.), Academic, New York.Google Scholar
  29. Ettenburg, A., Pettit, H. O., Bloom, F. E., and Koob, G. F. (1982) Heroin and cocaine intravenous self-administration in rats: Mediation by separate neural systems.Psychopharmacology 78, 204–209.CrossRefGoogle Scholar
  30. Feigenbaum, L. A., Graybiel, A. M., Vonsattel, J. P., Richardson, E. P., and Bird, E. D. (1986) Striosomal markers in the striatumin Huntington’s disease.Soc. Neurosci. Abstracts 12.Google Scholar
  31. Ferrante, R. J., Kowall, N. W., Beal, M. F., Richardson, E. P., Bird, E. D., and Martin, J. B. (1985) Selective sparing of a class of striatal neurons in Huntington’s disease.Science 230, 561–563.PubMedCrossRefGoogle Scholar
  32. Ferrante, R. J., Kowall, N. W., Richardson, E. P., Bird, E. D., and Martin, J. B. (1986) Topography of enkephalin, substance P and acetylcholinesterase staining in Huntington’s disease striatum.Neurosci. Lett. 71, 283–288.PubMedCrossRefGoogle Scholar
  33. Ferrante, R. J., Kowall, N. W., Beal, M. F., et al. (1987) Morphological and histochemical characteristics of a spared subset of striatal neurons in Huntington’s disease.J. Neuropathol. Exp. Neurol. 46, 12–27.PubMedCrossRefGoogle Scholar
  34. Folstein, S. E. (in press) Disease of the cuadate: A model of manic depressive disorder, inFunction and Dysfunction of the Basal Ganglia (Franks et al., eds.), Manchester University Press, Manchester, England.Google Scholar
  35. Folstein, S. E., Folstein, M. F., and McHugh, P. R. (1979) Psychiatric syndromes in Huntington’s disease, inAdvances in Neurology (Chase, T. N., Wexler, N. S., and Barbeau, A., eds.), Raven, New York, pp. 281–289.Google Scholar
  36. Folstein, S. E., Abbott, M. H., Chase, G. A., Jensen, B. A., and Folstein, M. F. (1983a) The association of affective disorder with Huntington’s disease in case series and in families.Psychol. Med. 13, 537–542.PubMedCrossRefGoogle Scholar
  37. Folstein, S. E., Franz, M. L., Jensen, B., Chase, G. A., and Folstein, M. F. (1983b) Conduct disorder and affective disorder among the offspring of patients with Huntington’s disease, inChildhood Psychopathology and Development (Guze, F., Earls, J., and Barrett, J. E., eds.), Raven, New York, pp. 231–245.Google Scholar
  38. Folstein, S. E., Abbott, M. H., Franz, M. L., Huang, S., Chase, G. A., and Folstein, M. F. (1984) Phenotypic heterogeneity in Huntington’s disease.J. Neurogenetic.,1, 175–184.CrossRefGoogle Scholar
  39. Folstein, S. E., Leigh, R. J., Parhad, I. M., and Folstein, M. F. (1986) The diagnosis of Huntington’s disease.Neurology 36, 1279–1283.PubMedGoogle Scholar
  40. Folstein, S. E., Chase, G. A., Wahl, W. E., McDonnell, A. M., and Folstein, M. F. (1987) Huntington’s disease: Clinical aspects of racial variation.Amer. J. Hum. Genet. 41, 168–179.PubMedGoogle Scholar
  41. Gerfen, C. R. (1984) The neostriatal matrix: Compartmentalization of corticostriatal input and striatonigral output systems.Nature 311, 461–464.PubMedCrossRefGoogle Scholar
  42. Gerfen, C. R. (1986) The developmental and biochemical basis of dual “patch” and “matrix” nigrostriatal dopaminergic systems in the rat.Neurosci. Abst 362.8.Google Scholar
  43. Gerfen, C. R., Baimbridge, K. G., and Thibault, J. (1987a) The neo-striatal mosaic: III Biochemical and developmental dissociation of patch-matrix striatal systems.J. Neurosci. 7, 3935–3944.PubMedGoogle Scholar
  44. Gerfen, C. R., Herkenham, M., and Thibault, J. (1987b) The neostriatal mosaic: II Patch- and matrix-directed mesostriatal dopaminergic and non-dopaminergic systems.J. Neurosci. 7, 3915–3934.PubMedGoogle Scholar
  45. Graybiel, A. M. and Ragsdale, C. W. (1978) Histochemically distinct compartments in the striatum of human, monkey and cat demonstrated by acetylcholiesterase staining.Proc. Natl. Acad. Sci. USA 75, 5723–5726.PubMedCrossRefGoogle Scholar
  46. Graybiel, A. M., and Ragsdale, C. W. (1983) Biochemical anatomy of the human striatum,Chemical Neuroanatomy (Emson, P. C., ed.) Raven, New York pp. 427–504.Google Scholar
  47. Gusella, J. F., Wexler, N. S., Conneally, P. M., Naylor, S. L., Anderson, M. A., Tanzi, R. E., Watkins, P. C., Ottina, K., Wallace, M. R., Sakaguchi, A. Y., Young, A. B., Shoulson, I., Bonilla, E., and Martin, J. B. (1983) A polymorphic DNA marker genetically linked to Huntington’s disease.Nature 306, 234–238.PubMedCrossRefGoogle Scholar
  48. Hoehn-Saric R. (1982) Neurotransmitters in anxiety.Arch. Gen. Psychiatry 39, 635–642.Google Scholar
  49. Huber, S. J., Paulson, G. W., and Shuttleworth, E. C. (1988) Depression in Parkinson’s disease.Neuropsychiatr. Neuropsychol. Behav. Neurol. 1, 47–51.Google Scholar
  50. Hunt, J. R. (1917) Progressive atrophy of the globus pallidus. (Primary atrophy of the pallidal system) A system disease of the paralysis agitans type, characterized by atrophy of the motor cells of the corpus striatum: A contribution to the funcitons of the corpus striatum.Brain 40, 58–148.CrossRefGoogle Scholar
  51. Huntington, G. (1872) On chorea.Adv. Neurol. 1, 33–35.Google Scholar
  52. Iversen, L. L., Rosser, M. N., and Reynolds, G. P. (1983) Loss of pigmented dopamine-β-hydrosylase positive cells from locus coeruleus in senile dementia of Alzheimer’s type.Neurosci. Lett. 39, 95–100.PubMedCrossRefGoogle Scholar
  53. Kane, J., Struve, F., Weinhold, P., et al. (1980) Strategy for the study of patients at high risk for tardive dyskinesia.Am. J. Psychol. 137, 1265–1267.Google Scholar
  54. Kemp, J. A., Foster, A. C., and Wong, E. H. F. (1987) Non-competitive antagonists of excitatory amino acid receptors.TINS,10, 294–298.Google Scholar
  55. Kiesselbach, G. (1914) Anatomischer Befund eines Falles von Huntingtonischer Chorea. Mschr.Psychiatr. Neurol. 35, 525–543.CrossRefGoogle Scholar
  56. Kish, S. J., Shannak, K. S., and Hornykiewicz, O. (1987) Elevated serotonin and reduced dopamine in subregionally divided Huntington’s disease striatum.Ann. Neurol. 22, 386–389.PubMedCrossRefGoogle Scholar
  57. Kurlan, R., Caine, E., Rubin, A., Nemeroff, C. B., Bissette, G., Zaczek, R., Coyle, J., Spielman, F. J., Irvine, D., and Shoulson, I. (1988) Cerebrospinal fluid correlates of depression in Huntington’s disease.Arch. Neurol. 45, 881–883.PubMedGoogle Scholar
  58. Lange, H. W. (1981) quantitative changes of telencephalon, diencephalon, and mesencephalon in Huntington’s chorea, post-encephalitic and idiopathic Parkinsonism.Verh. Anat. Ges. 75, 923–125.Google Scholar
  59. Lange, H. and Thorner, G. (1974) Zur Neuroanatomie and Neuropathologie des Corpus Striatum, Globus Pallidus und Nucleus Subthalamicus beim Mefxhen. Eine morphometrischstatistische Strukturanalyse at 13 Normal- und 15 Choreage-hirnen (unpublished).Google Scholar
  60. Lange, H., Thorner, G., Hopf, A., and Schroeder, K. F. (1976) Morphometric studies of the neuropathological changes in choreatic diseases.J. Neurol. Sci. 28, 401–425.PubMedCrossRefGoogle Scholar
  61. Lloyd, K. G., Thuret, F., and Pilc, A. (1985) Upregulation of Gamma-aminobutyric acid (GABA) B binding sites in rat frontal cortex: a common action of repeated administration of different classes of antidepressants and electro-shock.J. Pharmacol. Exp. Ther. 235, 191–199.PubMedGoogle Scholar
  62. Lloyd, K. G., Zivkovic, B., Scatton, B., Morselli, P. L., and Bartholini, G. (1989) The GABAergic hypothesis of depression.Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 13, 341–351.CrossRefGoogle Scholar
  63. Lodge, D., Aram, J. A., Church, J., Davies, S. N., Martin, D., O’Shaughnessy, C. T., and Zeman, S. (1987) Excitatory aminoacids and PCP like drugs.Neurol. Neurobiol. 24, 83–90.Google Scholar
  64. Lucas, D. R. and Newhouse, P. (1957) The toxic effect of sodiuml-glutamate on the inner layers of the retins.Arch. Opthalmol. 58, 193–201.Google Scholar
  65. Malick, J. B., Enna, S. J., and Yamamura, H. I. (1983)Anxiolytics: Neurochemical, Behavioral and Clinical Perspectives, Raven, New York.Google Scholar
  66. Marshall, P. E., Landis, D. M. D., and Zalneraitis, E. (1983) Immunocytochemical studies of substance P and leucine-enkephalinin Huntington’s disease.Brain Res. 298, 11–26.CrossRefGoogle Scholar
  67. Martin, J. B. (1984) Huntington’s disease: New approaches to an old problem.Neurology 34, 1059–1072.PubMedGoogle Scholar
  68. Mazziotta, J. C., Phelps, M. E., Pahl, J. J., et al. (1987) Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington’s disease. inEng. J. Medicine 316, 357–362.Google Scholar
  69. McCaughey, W. T. E. (1961) The pathological spectrum of Huntington’s chorea.J. Nerv. Ment. Dis. 133, 91–103.Google Scholar
  70. McGeer, E. G., and McGeer, P. L. (1976) Duplication of biochemical changes of Huntington’s chorea,Progress in Neurogenetics (Barbeau A. and Brunette T. R., eds.) Excerpta Medica Foundation, Amsterdam pp. 645–650.Google Scholar
  71. McHugh, P. R. (in press) The Basal Ganglia: The region, the integration of its systems and implications for psychiatry and neurology, inFunction and Dysfunction of the Basal Ganglia (Franks et al., eds) Manchester University Press, Manchester, EnglandGoogle Scholar
  72. McHugh, P. R. and Folstein, M. F. (1975) Psychiatric syndromes of Huntington’s chorea: A clinical and phenomenologic study, inPsychiatric Aspects of Neurologic Disease (Benson D. F. and Blumer, D., eds.) Grune and Stratton, New York.Google Scholar
  73. Melamed, E., Hefti, F., and Bird, E. D. (1982) Huntington chorea is not associated with hyperactivity of nigrostriatal dopaminergic neurons: Studies in postmortem tissues and in rats with kainic acid lesions.Neurology 32, 640–644.PubMedGoogle Scholar
  74. Minski, L. and Guttman, E. (1938) Huntington’s chorea: A study of thirty-four families.J. Ment. Sci. 84, 21–96.Google Scholar
  75. Morselli, P. L., Priore, P., Loeb, C., Albano, C., Nielsen, N. P., Serrati, C., and Musch, B. (1988) Antidepressant activity of progabide and fengabine, inNew Directions in Affective Disorders (Lerer, B. and Gershon, S., eds.). Springer-Verlag, NY.Google Scholar
  76. Nakata, Y., Chang, K. J., Mitchell, C. L., and Hong, J. S. (1985) Repeated electroconvulsive shock down regulates the opioid receptors in rat brain.Brain Res. 346, 160–163.PubMedCrossRefGoogle Scholar
  77. Nauta, W. J. H. and Domesick, V. B. (1981) Ramifications of the limbic system,Psychiatry and Biology of the Human Brain (Matthysse S., ed.) Elsevier North Holland Biomedical, New York.Google Scholar
  78. Nauta, H. J. W. (1986) The relationship of the basal ganglia to the limbic system,Extrapyramidal Disorders (Vinken P. J., Bruyn, G. W., and Klawans H. L., eds.) Elsevier Science, New York pp. 19–31.Google Scholar
  79. Nauta, W. J. H. and Feirtag, M. (1986)Fundamental Neuroanatomy. Freeman, New York.Google Scholar
  80. Nemeroff, C. B., Youngblood, W. W., Manberg, P. J., et al. (1983) Regional brain concentrations of neuropeptides in Huntington’s chorea and schizophrenia.Science 221, 972–975.PubMedCrossRefGoogle Scholar
  81. Olney, J. W. (1969) Glutamate-induced retinal degeneration in neonatal mice: Electronmicroscopy of acutely evolving lesions.J. Neuropathol. Exp. Neurol. 28, 455–474.PubMedCrossRefGoogle Scholar
  82. Oyanagi, K., Takeda, S., Takahashi, H., Ohama, E., and Ikuta, F. (1989) A quantitative investigation of the substantia nigra in Huntington’s disease.Ann. Neurol. 26, 13–19.PubMedCrossRefGoogle Scholar
  83. Pasik, P., Pasik, T. and DiFiglia, M. (1979) The internal organization of the neostriatum in mammals, inThe Neostriatum (Divac J. and Oberg R. G., eds.) pp. 5–36.Google Scholar
  84. Penney, Jr., J. B. and Young, A. B. (1982) Quantitative autoradiography in neurotransmitter receptors in Huntington disease.Neurology 32, 1391–1395.PubMedGoogle Scholar
  85. Perry, T. L., Hansen, S. and Kloster, M. (1973) Huntington’s chorea: Deficiency of gamma-aminobutyric acid in brain.N. Engl. J. Med. 288, 337–342.PubMedCrossRefGoogle Scholar
  86. Rabins, P. (1982) The psychopathology of Parkinson’s disease.Compr. Psychiatry 23, 421–428.PubMedCrossRefGoogle Scholar
  87. Reiner, A., Albin, R. L., Anderson, K. D., D’Amato, C. J., Penney, J. B., and Young, A. B. (1988) Differential loss of striatal projection neurons in Huntington’s disease.Proc. Natl. Acad. Sci. USA,85, 5733–5737.PubMedCrossRefGoogle Scholar
  88. Ribak, C. E., Vaughn, J. E., and Roberts, E. (1979) The GABA neurons and their axon terminals in the rat corpus striatum as demonstrated by GAD immunocytochemistry.J. Comp. Neurol. 187, 267–284.CrossRefGoogle Scholar
  89. Robinson, M. B. and Coyle, J. T. (1987) Glutamate and related acidic excitatory neurotransmitters: From basic science to clinical application.Fed Soc. Exp. Biol. 1, 446–455.Google Scholar
  90. Rodda, R. A. (1981) Cerebellar atrophy in Huntington’s disease.J. Neurol. Sci. 50, 147–157.PubMedCrossRefGoogle Scholar
  91. Schwarcz, R., Kohler, C., Mangano, R. M., and Neophytides, A. N. (1981) Glutamate-induced neuronal degeneration: Studies on the role of glutamate re-uptake, inGlutamate as a Neurotransmitter (DiChiara, G. D. and Gessa, G. L. eds.)27, 403–412.Google Scholar
  92. Shoulson, I., Chase, T. N., Roberts, E., and Van Balgooy, J. N. (1975) Huntington’s disease: treatment with imidazole-4-acetic acid.N. Engl. J. Med. 293, 504, 505.PubMedGoogle Scholar
  93. Shoulson, I., Kartzinel, R., and Chase, T. N. (1976) Huntington’s disease: Treatment with dipropylacetic acid and gamma-aminobutyric acid.Neurology 26, 61–63.PubMedGoogle Scholar
  94. Spokes, E. G. S. (1980) Neurochemical alterations in Huntington’s chorea: A study of postmortem brain tissue.Brain 103, 179–210.PubMedCrossRefGoogle Scholar
  95. Trautner, R. J., Cummings, J. L., Read, S. L., and Benson, D. F. (1988) Idiopathic basal ganglia calcification and organic mood disorder.Am. J. Psychiatry 145, 350–353.PubMedGoogle Scholar
  96. Vonsattel, J. P., Meyers, R. H., Stevens, T. J., Ferrante, R. J., Bird, E. D., and Richardson, E. P., Jr. (1985) Neuropathological classification of Huntington’s disease.J. Neuropathol. Exp. Neurol. 44, 559–577.PubMedCrossRefGoogle Scholar
  97. Wexler, N. S., Young, A. B., Tanzi, R. E., Travers, H., Starosta-Rubinstein, S., Penney, J. B., Snodgrass, S. R., Shoulson, I., Gomez, F., Ramos, A., Penchaszadeh, G. K., Moreno, U., Gibbons, K., Faryniarz, A., Hobbs, W., Anderson, M. A., Bonilla, E., Conneally, T. M., and Guzella, J. F. (1987) Homozygotes for Huntington’s disease.Nature 326, 194–197.PubMedCrossRefGoogle Scholar
  98. Whitehouse, P. J., Jones, B. E., Trifiletti, R. R., Folstein, S. E., Price, D. L., and Kuhar, M. J. (1985) Neurotransmitter receptor alterations in Huntington’s disease: Autoradiographic studies.Ann. Neurol.,18, 202–210.PubMedCrossRefGoogle Scholar
  99. Wolfe, J., Granholm, E., Butters, N., Saunders, E., and Janowsky, D. (1987) Verbal memory deficits associated with major affective disorders: a comparison of unipolar and bipolar patients.J. Aff. Dis. 13, 83–92.CrossRefGoogle Scholar
  100. Young, A. B., Greenamyre, J. T., Hollingswoth, Z., Albin, R., D’Amato, C., Shoulson, I., and Penney, J. B. (1988) NMDA receptor losses in putamen from patients with Huntington’s disease (HD)Science 241, 981–983.PubMedCrossRefGoogle Scholar
  101. Young, A. B., Pan, H. S., Ciliax, B. J., and Penney, J. B. (1984) GABA and Benzodiazepine receptors in basal ganglion function.Neurosci. Lett. 47, 361–367.PubMedCrossRefGoogle Scholar
  102. Young, A. B., Penney, J. B., Starosta-Rubenstein, S., Markel, B., Berent, S., Rothley, J., Betley, A., and Hickwa, R. (1987) Normal caudate glucose metabolism in persons at risk for Huntington’s disease.Arch. Neurol. 44, 254–257.PubMedGoogle Scholar
  103. Zech, M., Roberts, G. W., Bogerts, B., Crow, T. J., and Polak, J. M. (1986) Neuropeptides in the amygdala of controls, schizophrenics and patients suffering from Huntington’s chorea: An immunohistochemical study.Acta Neuropathol. 71, 259–266.PubMedCrossRefGoogle Scholar
  104. Zweig, R. M., Ross, C. A., Hedreen, J. C., et al. (1988) The neuropathology of aminergic nuclei in Alzheimer’s disease.Ann. Neurol. 24, 233–242.PubMedCrossRefGoogle Scholar
  105. Zweig, R. M., Ross, C. A., Hedreen, J. C., Peyser, C. E., Cardillo, J. E., Cohen, M., Folstein, S. E., and Price, D. L. (1989) Clinical and pathological correlates of locus coeruleus pathology in Parkinson’s disease and Huntington’s disease.Soc. Neurosci. Abstracts 369.1, 931.Google Scholar

Copyright information

© Humana Press Inc. 1990

Authors and Affiliations

  • Carol Efron Peyser
    • 1
  • Susan E. Folstein
    • 1
  1. 1.Department of PsychiatryJohns Hopkins University of School of MedicineBaltimore

Personalised recommendations