Quantitative Cytoarchitectonic Findings in Postmortem Brain Tissue from Mood Disorder Patients

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

Abstract

A considerable body of pharmacological and neurochemical literature has accumulated on affective disorders. Until recently, however, there have been no quantitative neuroanatomical studies of these disorders at the microscopic level. Clinical neuroimaging studies and pre-clinical animal studies, however, strongly suggest that cell atrophy, cell loss or impairments in neuroplasticity and cellular resilience may underlie the neurobiology of primary mood disorders (i.e., major depressive disorder and bipolar manic-depressive disorder).

Recent quantitative cytoarchitectonic studies on postmortem tissues from patients with mood disorders provide direct evidence that mood disorders are characterized by specific changes in the number, density or size of both neurons and glial cells. Although published reports are scarce and based on rather small sample sizes, these studies are surprisingly consistent in revealing previously unrecognized reductions in glial cell number and density as well as alterations in the density and/or size of specific types of cortical neurons in frontal limbic brain regions.

This chapter reviews the current findings from stereological and morphometric postmortem studies on glia and neurons in primary mood disorders. The relevance of cellular changes in mood disorders to dysfunctional monoaminergic and glutamatergic circuits and a possible role of neurotrophic and neuroprotective factors in cell pathology is discussed. A possible link between cellular changes in mood disorders and the action of psychotherapeutic drugs is suggested as well.

Keywords

Prefrontal Cortex Anterior Cingulate Cortex Mood Disorder Dorsal Raphe Neuronal Density 
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. Agam G, Levine J. Glycogen synthase kinase-3–a new target for lithium’s effects in bipolar patients? (Editorial). Human Psychopharmacol. Clin Exp 1998; 13: 463–465Google Scholar
  2. Altshuler LL, Conrad A, Hauser P, et al. Reduction of temporal lobe volume in bipolar disorder: a preliminary report of magnetic resonance imaging [letter]. Arch Gen Psychiatry 1991; 48: 482–3.PubMedGoogle Scholar
  3. Anand A, Charney DS. Norepinephrine dysfunction in depression. J Clin Psychiatry 2000; 61: 16–24.PubMedGoogle Scholar
  4. Arango V, Underw000d MD, Gubbi AV, Mann JJ. Localized alterations in pre-and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims. Brain Res 1995; 688: 121–133.PubMedGoogle Scholar
  5. Auer DP, Putz B, Kraft E, Lipinski B, Schill J, Holsboer F. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry 2000; 47: 305–13.PubMedGoogle Scholar
  6. Baumann B, Danos P, Krell D, et al. Unipolar-bipolar dichotomy of mood disorders is supported by noradrenergic brainstem system morphology. J Affect Disord 1999; 54: 217–24.PubMedGoogle Scholar
  7. Baxter LR, Schwartz JM, Phelps ME, et al. Reduction of prefrontal cortex glucose metabolism common to three types of depression. Arch Gen Psychiatry 1989; 46: 243–250.PubMedGoogle Scholar
  8. Bench CJ, Friston KJ, Brown RG, Frackowiak RSJ, Dolan RI. Regional cerebral blood flow in depression measured by positron emission tomography: the relationship with clinical dimensions. Psychol Med 1993; 23: 579–590.PubMedGoogle Scholar
  9. Benes FM, Kwok EW, Vincent SL, Todtenkopf MS. A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives. Biol Psychiatry 1998; 44: 88–97.PubMedGoogle Scholar
  10. Benes FM, Vincent SL, Todtenkopf MS. The Density of Pyramidal and Nonpyramidal Neurons in Anterior Cingulate Cortex of Schizophrenic and Bipolar Subjects. Biol Psychiatry 2001;in press.Google Scholar
  11. Bertolino A. Dysregulation of dopamine and pathology of prefrontal neurons: neuroimaging studies in schizophrenia and related animal models. Epidemiol Psichiatr Soc 1999; 8: 248–54.PubMedGoogle Scholar
  12. Bertolino A, Frye M, Callicott JH, et al. Neuronal pathology in the hippocampal area of patients with bipolar disorder. Biol Psychiatry 1999; 45: 135S.Google Scholar
  13. Bijur GN, De Sarno P, lope RS. Glycogen synthase kinase-3beta facilitates staurosporine-and heat shock-induced apoptosis. Protection by lithium. J Biol Chem 2000; 275: 7583–90.PubMedGoogle Scholar
  14. Biver F, Goldman S, Delvenne V, et al. Frontal and parietal metabolic disturbances in unipolar depression. Biol Psychiatry 1994; 36: 381–388.PubMedGoogle Scholar
  15. Blier P, de Montigny C. Current advances and trends in the treatment of depression [see comments]. Trends Pharmacol Sci 1994; 15: 220–6.PubMedGoogle Scholar
  16. Blumberg HP, Stern E, Ricketts S, et al. Rostral and orbital prefrontal cortex dysfunction in the manic state of bipolar disorder. Am J Psychiatry 1999; 156: 1986–8.PubMedGoogle Scholar
  17. Botteron KN, Vannier MW, Geller B, Todd RD, Lee BC. Preliminary study of magnetic resonance imaging characteristics in 8- to 16-year-olds with mania J Am Acad Child Adolesc Psychiatry 1995; 34: 742–9.Google Scholar
  18. Bowley MP, Drevets WC, Ongur D, Price JL. Glial chnages in the amygdala and entorhinal cortex in mood disorders. Soc Neurosci Abstr 2000; 26: 23–13.Google Scholar
  19. Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS. Hippocampal volume reduction in major depression. Am J Psychiatry 2000; 157: 115–8.PubMedGoogle Scholar
  20. Buchsbaum MS, Wu J, DeLisi LE, et al. Frontal cortex and basal ganglia metabolic rates assessed by positron emission tomography with [18F]2-deoxyglucose in affective illness. J Affect Disord 1986; 10: 137–52.PubMedGoogle Scholar
  21. Chen G, Rajkowska G, Du F, Seraji-Bozorgzad N, Manji HK. Enhancement of hippocampal neurogenesis by lithium. J Neurochem 2000; 75: 1729–34.PubMedGoogle Scholar
  22. Chen G, Zeng WZ, Yuan PX, et al. The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bc1–2 in the CNS. J Neurochem 1999; 72: 879–82.PubMedGoogle Scholar
  23. Chen RW, Chuang DM. Long term lithium treatment suppresses p53 and Bax expression but increases Bc1–2 expression. A prominent role in neuroprotection against excitotoxicity. J Biol Chem 1999; 274: 6039–42.Google Scholar
  24. Coffey CE, Wilkinson WE, Weiner RD, et al. Quantitative cerebral anatomy in depression. A controlled magnetic resonance imaging study. Arch Gen Psychiatry 1993; 50: 7–16.PubMedGoogle Scholar
  25. Coffman JA, Bornstein RA, Olson SC, Schwarzkopf SB, Nasrallah HA. Cognitive impairment and cerebral structure by MRI in bipolar disorder. Biol Psychiatry 1990; 27: 1188–96.PubMedGoogle Scholar
  26. Cotter D, Mackay D, Landau S, Kerwin R, Everall I. Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry 2001; 58: 545–553.PubMedGoogle Scholar
  27. Coyle JT, Schwarcz R. Mind glue: implications of glial cell biology for psychiatry. Arch Gen Psychiatry 2000; 57: 90–3.PubMedGoogle Scholar
  28. Deicken RF, Fein G, Weiner MW. Abnormal frontal lobe phosphorous metabolism in bipolar disorder. Am J Psychiatry 1995; 152: 915–8.PubMedGoogle Scholar
  29. Diekmann S, Baumann B, Schmidt U, Bogerts B. Significant reduction of calretinin-IR neurons in layer II in the anterior cingulate cortex in subjects with affective disorders. Soc Neurosci Abstr 1998; 24: 386. 5.Google Scholar
  30. Drevets W, Price J, Simpson JR J, et al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature 1997; 386: 824–7.PubMedGoogle Scholar
  31. Drevets WC. Prefrontal cortical-amygdalar metabolism in major depression. Ann N Y Acad Sci 1999; 877: 614–37.PubMedGoogle Scholar
  32. Duman RS, Malberg J, Nakagawa S, D’Sa C. Neuronal plasticity and survival in mood disorders. Biol Psychiatry 2000; 48: 732–9.PubMedGoogle Scholar
  33. Eastwood SL, Harrison PJ. Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs. Mol Psychiatry 2000; 5: 425–32.PubMedGoogle Scholar
  34. Elkis H, Friedman L, Wise A, Meltzer HY. Meta-analyses of studies of ventricular enlargement and cortical sulcal prominence in mood disorders. Arch Gen Psy 1995; 52: 735–746.Google Scholar
  35. Erickson JT, Brosenitsch TA, Katz DM. Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor Are Required Simultaneously for Survival of Dopaminergic Primary Sensory Neurons In Vivo. J Neurosci 2001; 21: 581–589.PubMedGoogle Scholar
  36. Friedman WJ, Olson L, Persson H. Cells that express brain-derived neurotrophic factor mRNA in the developing postnatal brain. Eur J Neurose 1991; 3: 688–697.Google Scholar
  37. George MS, Ketter TA, Post RM. SPECT and PET imaging in mood disorders. J Clin Psychiatry 1993;54 Suppl: 6–13.Google Scholar
  38. Ghosh A, Carnahan J, Greenberg ME. Requirement for BDNF in activity-dependent survival of cortical neurons. Science 1994; 263: 1618–23.PubMedGoogle Scholar
  39. Gould E, Reeves AJ, Graziano MS, Gross CG. Neurogenesis in the neocortex of adult primates. Science 1999; 286: 548–52.PubMedGoogle Scholar
  40. Gould E, Tanapat P. Stress and hippocampal neurogenesis. Biol Psychiatry 1999; 46: 1472–1479.PubMedGoogle Scholar
  41. Griffith R, Sutin J. Reactive astrocyte formation in vivo is regulated by noradrenergic axons. J Comp Neural 1996; 371: 362–75.Google Scholar
  42. Gundersen HJG, Bagger P, Bendtsen TF, et al. The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. Acta Pathol Microbiol Immunol Scand 1988; 96: 857–881.Google Scholar
  43. Hauser P, Altshuler LL, Berrettini W, Dauphinais ID, Gelernter J, Post RM. Temporal lobe measurement in primary affective disorder by magnetic resonance imaging. J Neuropsychiatry Clin Neurosci 1989; 1: 128–34.PubMedGoogle Scholar
  44. Hedreen JC, Peyser CE, Folstein SE, Ross CA. Neuronal loss in layers V and VI of cerebral cortex in Huntington’s disease. Neurosci Lett 1991; 133: 257–261.PubMedGoogle Scholar
  45. Holsboer F, Spengler D, Heuser I. The role of corticotropin-releasing hormone in the pathogenesis of Cushing’s disease, anorexia nervosa, alcoholism, affective disorders and dementia Prog Brain Res 1992; 93: 385–417.Google Scholar
  46. Huntley GW, Benson DL, Jones EG, Isackson PJ. Developmental expression of brain derived neurotrophic factor mRNA by neurons of fetal and adult monkey prefrontal cortex. Brain Res Dev Brain Res 1992; 70: 53–63.PubMedGoogle Scholar
  47. Jeste DV, Heaton SC, Paulsen JS, Ercoli L, Harris J, Heaton RK. Clinical and neuropsychological comparison of psychotic depression with nonpsychotic depression and schizophrenia [see comments]. Am J Psychiatry 1996; 153: 490–6.PubMedGoogle Scholar
  48. Johnston-Wilson NL, Sims CD, Hofmann JP, et al. Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. The Stanley Neuropathology Consortium. Mol Psychiatry 2000; 5: 142–9.PubMedGoogle Scholar
  49. Jope RS. Anti-bipolar therapy. mechanism of action of lithium. Mol Psychiatry 1999; 4: 1 1728.Google Scholar
  50. Kasir SA, Underwood MD, Bakalian MJ, Mann JJ, Arango V. 5-HT1A binding in dorsal and median raphe nuclei of suicide victims. Soc Neurosci Abstr 1998; 24: 505. 3.Google Scholar
  51. Kato T, Shioiri T, Murashita J, et al. Lateralized abnormality of high energy phosphate metabolism in the frontal lobes of patients with bipolar disorder detected by phase-encoded 31P-MRS. Psychol Med 1995; 25: 557–66.PubMedGoogle Scholar
  52. Kawamoto Y, Nakamura S, Kawamata T, Akiguchi I, Kimura J. Cellular localization of brain-derived neurotrophic factor-like immunoreactivity in adult monkey brain. Brain Res 1999; 821: 341–349.PubMedGoogle Scholar
  53. Khan ZU, Koulen P, Rubinstein M, Grandy DK, Goldman-Rakic PS. An astroglia-linked dopamine D2-receptor action in prefrontal cortex. Proc Nati Acad Sci USA 2001; 98: 1964–1969.Google Scholar
  54. Klimek V, Stockmeier C, Overholser J, et al. Reduced levels of norepinephrine transporters in the locus coeruleus in major depression. J Neurosci 1997; 17: 8451–8.PubMedGoogle Scholar
  55. Korbo L. Glial cell loss in the hippocampus of alcoholics. Alcohol Clin Exp Res 1999; 23: 164–8.PubMedGoogle Scholar
  56. Krimer LS, Jakab RL, Goldman-Rakic PS. Quantitative three-dimensional analysis of the catecholaminergic innervation of identified neurons in the macaque prefrontal cortex. J Neurosci 1997; 17: 7450–61.PubMedGoogle Scholar
  57. Levine S, Saltzman A, Klein AW. Proliferation of glial cells in vivo induced in the neural lobe of the rat pituitary by lithium. Cell Prolif 2000; 33: 203–7.PubMedGoogle Scholar
  58. Lewis DA. The catecholaminergic innervation of primate prefrontal cortex. J Neural Trans 1992; 36: 179–200.Google Scholar
  59. Lim KO, Rosenbloom MJ, Faustman WO, Sullivan EV, Pfefferbaum A. Cortical gray matter deficit in patients with bipolar disorder. Schizophr Res 1999; 40: 219–27.PubMedGoogle Scholar
  60. Lu R, Song L, Jope RS. Lithium attenuates p53 levels in human neuroblastoma SH-SY5Y cells. Neuroreport 1999; 10: 1123–5.PubMedGoogle Scholar
  61. Lucassen PJ, Salehi A, Pool CW, Gonatas NK, Swaab DF. Activation of vasopressin neurons in aging and Alzheimer’s disease. J Neuroendocrinol 1994; 6: 673–9.PubMedGoogle Scholar
  62. Malberg JE, Eisch AJ, Nestler EJ, Duman RS. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 2000; 20: 9104–10.PubMedGoogle Scholar
  63. Manji HK, Moore GJ, Chen G. Lithium up-regulates the cytoprotective protein Bd-2 in the CNS in vivo: a role for neurotrophic and neuroprotective effects in manic depressive illness. J Clin Psychiatry 2000a; 61: 82–96.PubMedGoogle Scholar
  64. Manji HK, Moore GJ, Rajkowska G, Chen G. Neuroplasticity and cellular resilience in mood disorders. Mol Psychiatry 2000b; 5: 578–93PubMedGoogle Scholar
  65. Marty S, Berzaghi Md, Berninger B. Neurotrophins and activity-dependent plasticity of cortical interneurons. Trends Neurosci 1997; 20: 198–202.PubMedGoogle Scholar
  66. Mayberg HS. Depression. In Mazziotta JC, Toga AW, Frackowiak RSJ (eds), Brain Mapping. The Disorders: Academic Press, 2000; pp 485–505.Google Scholar
  67. Mazer C, Muneyyirci J, Taheny K, Raio N, Borella A, WhitakerAzmitia P. Serotonin depletion during synaptogenesis leads to decreased synaptic density and learning deficits in the adult rat: A possible model of neurodev elopmental disorders with cognitive deficits. Brain Res 1997; 760X: 68X - 73X.Google Scholar
  68. Miguel-Hidalgo JJ, Baucom C, Dilley G, et al. Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder. Biol Psychiatry 2000; 48: 861–73.PubMedGoogle Scholar
  69. Moore GJ, Bebchuk JM, Hasanat K, et al. Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2’s neurotrophic effects? Biol Psychiatry 2000a; 48: 1–8.PubMedGoogle Scholar
  70. Moore GJ, Bebchuk JM, Wilds IB, Chen G, Menji HK. Lithium-induced increase in human brain grey matter. Lancet 2000b; 356: 1241–2.PubMedGoogle Scholar
  71. Murer MG, Boissiere F, Yan Q, et al. An immunohistochemical study of the distribution of brain-derived neurotrophic factor in the adult human brain, with particular reference to Alzheimer’s disease. Neuroscience 1999; 88: 1015–32.PubMedGoogle Scholar
  72. Nowak G, Ordway GA, Paul IA. Alterations in the N-methyl-D-aspartate (NMDA) receptor complex in the frontal cortex of suicide victims. Brain Res 1995; 675: 157–64.PubMedGoogle Scholar
  73. Ohgoh M, Kimura M, Ogura H, Katayama K, Nishizawa Y. Apoptotic cell death of cultured cerebral cortical neurons induced by withdrawal of astroglial trophic support. Experimental Neurology 1998; 149: 51–63.PubMedGoogle Scholar
  74. Ongur D, Drevets WC, Price JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA 1998; 95: 13290–5.PubMedGoogle Scholar
  75. Orlovskaya DD, Vikhreva OV, Zimina IS, Denisov DV, Uranova NA. Ultrastructural Dystrophic chnages of oligodendroglial cells in autopsied prefrontal cortex and striatum in schizophrenia: a morphometric study. Schizophr Res. 1999; 36: 82–83.Google Scholar
  76. Orlovskaya DD, Vostrikov VM, Rachmanova NA, Uranova NA. Decreased numerical density of oligodendroglial cells in postmortem prefrontal cortex in schizophrenia, bipolar affective disorder and major depression. Schizophr Res. 2000; 41: 105.Google Scholar
  77. Pazos A, Probst A, Palacios J. Serotonin receptors in the human brain-III. Autoradiographic mapping ofserotonin-1 receptors. Neuroscience 1987; 21: 97–122.PubMedGoogle Scholar
  78. Pearlson GD, Barta PE, Powers RE, et al. Ziskind-Somerfeld Research Award 1996. Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder. Biol Psychiatry 1997; 41: 1–14.PubMedGoogle Scholar
  79. Pfrieger FW, Barres BA. Synaptic efficacy enhanced by glial cells in vitro. Science 1997; 277: 1684–7.PubMedGoogle Scholar
  80. Prange AJ. The pharmacology and biochemistry of depression. Dis New Syst 1964; 25: 217221.Google Scholar
  81. Purba JS, Hoogendijk WJ, Hofman MA, Swaab DF. Increased number of vasopressin-and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression. Arch Gen Psychiatry 1996; 53: 137–43.PubMedGoogle Scholar
  82. Raadsheer FC, Hoogendijk WJ, Stam FC, Tilders FJ, Swaab DF. Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology 1994; 60: 436–44.PubMedGoogle Scholar
  83. Raadsheer FC, van Heerikhuize JJ, Lucassen PJ, Hoogendijk WJ, Tilders FJ, Swaab DF. Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer’s disease and depression. Am J Psychiatry 1995; 152: 1372–1376.PubMedGoogle Scholar
  84. Rajkowska G. Histopathology of the prefrontal cortex in major depression: what does it tell us about dysfunctional monoaminergic circuits? Prog Brain Res 2000a; 126: 397–412.PubMedGoogle Scholar
  85. Rajkowska G. Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry 2000b; 48: 766–77.PubMedGoogle Scholar
  86. Rajkowska G, Halaris A, Selemon LD. Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder. Biol. Psychiatry 2001; 49: 74 1752.Google Scholar
  87. Rajkowska G, Miguel-Hidalgo JJ, Wei J, et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry 1999a; 45: 1085–98.PubMedGoogle Scholar
  88. Rajkowska G, Miguel-Hidalgo JJ, Wei J, Stockmeier CA. Reductions in glia distinguish orbitofrontal region from dorsolateral prefrontal cortex in schizophrenia. Soc Neurosci Abstr 1999b; 25: 818.Google Scholar
  89. Rajkowska G, Selemon LD, Goldman-Rakic PS. Neuronal and glial somal size in the prefrontal cortex: a postmortem morphometric study of schizophrenia and Huntington disease. Arch Gen Psychiatry 1998; 55: 215–24.PubMedGoogle Scholar
  90. Rajkowska G, Wei J, Miguel-Hidalgo JJ, Stockmeier C. Glial and neuronal pathology in rostral orbitofrontal cortex in schizophrenic postmortem brain. Schizophr Res. 1999c; 36: 84.Google Scholar
  91. Rocha E, Achaval M, Santos P, Rodnight R. Lithium treatment causes gliosis and modifies the morphology of hippocampal astrocytes in rats. Neuroreport 1998; 9: 3971–4.PubMedGoogle Scholar
  92. Rocha E, Rodnight R. Chronic administration of lithium chloride increases iormunodetectable glial fibrillary acidic protein in the rat hippocampus. J Neurochem 1994; 63: 1582–4.PubMedGoogle Scholar
  93. Rosoklija G, Toomayan G, Ellis SP, et al. Structural abnormalities of subicular dendrites in subjects with schizophrenia and mood disorders: preliminary findings. Arch Gen Psychiatry 2000; 57: 349–56.PubMedGoogle Scholar
  94. Rothstein JD, Dykes-Hoberg M, Pardo CA, et al. Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 1996; 16: 675–86.PubMedGoogle Scholar
  95. Rutherford LC, Nelson SB, Turrigiano GG. BDNF has opposite effects on the quantal amplitude of pyramidal neuron and interneuron excitatory synapses. Neuron 1998; 21: 521–30.PubMedGoogle Scholar
  96. Sapolsky RM. The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death. Biol Psychiatry 2000; 48: 755–65.PubMedGoogle Scholar
  97. Schildkraut H. The cathecolamine hypothesis of affective disorders: a review of suppoting evidence. Am J Psychiat 1965; 122: 509–522.PubMedGoogle Scholar
  98. Selemon LD, Goldman-Rakic PS. Longitudinal topography and interdigitation of corticostriatal projections in the rhesus monkey. J Neuroscience 1985; 5: 776–794.Google Scholar
  99. Selemon LD, Goldman-Rakic PS. The reduced neuropil hypothesis: a circuit based model of schizophrenia [In Process Citation]. Biol Psychiatry 1999; 45: 17–25.PubMedGoogle Scholar
  100. Selemon LD, Lidow MS, Goldman-Rakic PS. Increased volume and glial density in primate prefrontal cortex associated with chronic antipsychotic drug exposure. Biol Psychiatry 1999; 46: 161–72.PubMedGoogle Scholar
  101. Selemon LD, Rajkowska G, Goldman-Rakic PS. Abnormally high neuronal density in the schizophrenic cortex: a morphometric analysis of prefrontal area 9 and occipital area 17. Arch Gen Psychiatry 1995; 52: 805–818.PubMedGoogle Scholar
  102. Selemon LD, Rajkowska G, Goldman-Rakic PS. Elevated neuronal density in prefrontal area 46 in brains from schizophrenic patients: application of a three-dimensional, stereologic counting method. J Comp Neurol 1998; 392: 402–12.PubMedGoogle Scholar
  103. Sesack SR, Hawrylak VA, Melchitzky DS, Lewis DA. Dopamine innervation of a subclass of local circuit neurons in monkey prefrontal cortex: ultrastructural analysis of tyrosine hydroxylase and parvalbumin immunoreactive structures. Cereb Cortex 1998; 8: 6 1422.Google Scholar
  104. Shankaranarayana Rao BS, Lakshmana MK, Meti BL, Raju TR. Chronic (-) deprenyl administration alters dendritic morphology of layer III pyramidal neurons in the prefrontal cortex of adult Bonnett monkeys. Brain Res 1999; 821: 218–223.PubMedGoogle Scholar
  105. Sheline YI, Gado MH, Price JL. Amygdala core nuclei volumes are decreased in recurrent major depression [published erratum appears in Neuroreport 1998 Jul 13;9(10):2436]. Neuroreport 1998; 9: 2023–8.Google Scholar
  106. Sheline YI, Sanghavi M, Mintun MA, Gado MH. Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci 1999; 19: 5034–43.PubMedGoogle Scholar
  107. Shimizu M, Nishida A, Zensho H, Yamawaki S. Chronic antidepressant exposure enhances 5hydroxytryptamine7 receptor-mediated cyclic adenosine monophosphate accumulation in rat frontocortical astrocytes. J Pharmacol Exp Ther 1996; 279: 1551–8.PubMedGoogle Scholar
  108. Shiraishi H, Koizumi J, Hori M, et al. A computerized tomographic study in patients with delusional and non-delusional depression. Jpn J Psychiat Neurol 1992; 46: 99–105.Google Scholar
  109. Smiley JF, Goldman-Rakic PS. Heterogenous targets of dopamine synapses in monkey prefrontal cortex demonstrated by serial section electron microscopy: a laminar analysis using the silver-enhanced diaminobenzidine sulfide (SEDS) immunolabeling technique. Cereb Cortex 1993; 3: 223–238.PubMedGoogle Scholar
  110. Smiley JF, Goldman-Rakic PS. Serotonergic axons in monkey prefrontal cerebral cortex synapse predominantly on interneurons as demonstrated by serial section electron microscopy. J Comp Neurol 1996; 367: 431–43.PubMedGoogle Scholar
  111. Soares J, Mann J. The anatomy of mood disorders-review of structural neuroimaging studies. Biol Psychiatry 1997; 41: 86–106.PubMedGoogle Scholar
  112. Stanford SC. Monoamines in response and adaptation to stress. In Stanford SC, Salmon P (eds), Stress: from synapse to syndrome. London: Academic Press, 1993; pp 282–332.Google Scholar
  113. Steingard RJ, Yurgelun-Todd DA, Hennen J, et al. Increased orbitofrontal cortex levels of choline in depressed adolescents as detected by in vivo proton magnetic resonance spectroscopy. Biol Psychiatry 2000; 48: 1053–61.PubMedGoogle Scholar
  114. Stockmeier CA, Dilley GE, Kulnane LS, Miguel-Hidalgo JJ, Rajkowska-Markow G. Morphometric evaluation of the midbrain dorsal raphe nucleus (DR) in suicide victims with major depression (MD). Soc Neurosc Abstr 1999; 25: 2098.Google Scholar
  115. Stockmeier CA, Shapiro LA, Dilley GE, Kolli TN, Friedman L, Rajkowska G. Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity. J Neurosci 1998; 18: 7394–401.PubMedGoogle Scholar
  116. Swaab DF, Hofman MA, Lucassen PJ, Purba JS, Raadsheer FC, Van de Nes JA. Functional neuroanatomy and neuropathology of the human hypothalamus. Anat Embryol (Berl) 1993; 187: 317–30.Google Scholar
  117. Tanaka K, Watase K, Manabe T, et al. Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science 1997; 276: 1699–702.PubMedGoogle Scholar
  118. Thierry AM, Le Douarin C, Penit J, Ferron A, Glowinski J. Variation in the ability of neuroleptics to block the inhibitory influence of dopaminergic neurons on the activity of cells in the rat prefrontal cortex. Brain Res Bull 1986; 16: 155–60.PubMedGoogle Scholar
  119. Tsacopoulos M, Magistretti PJ. Metabolic coupling between glia and neurons. J Neurosci 1996; 16: 877–85.PubMedGoogle Scholar
  120. Tsai G, Coyle JT. N-acetylaspartate in neuropsychiatric disorders. Prog Neurobiol 1995; 46: 531–40.PubMedGoogle Scholar
  121. Ullian EM, Sapperstein SK, Christopherson KS, Barres BA. Control of Synapse Number by Glia. Science 2001; 291: 657–661.PubMedGoogle Scholar
  122. Underwood MD, Khaibulina AA, Ellis SP, et al. Morphometry of the dorsal raphe nucleus serotonergic neurons in suicide victims. Biol Psychiatry 1999; 46: 473–83.PubMedGoogle Scholar
  123. Wang Y, Sheen VL, Macklis JD. Cortical intemeurons upregulate neurotrophins in vivo in response to targeted apoptotic degeneration of neighboring pyramidal neurons. Exp Neurol 1998; 154: 389–402.PubMedGoogle Scholar
  124. Watanabe Y, Gould E, McEwen BS. Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res 1992; 588: 341–5.PubMedGoogle Scholar
  125. West MJ. New stereological methods for counting neurons. Neurobiol Aging 1993; 14: 27585.Google Scholar
  126. Whitaker-Azmitia P, Clarke C, Azmitia E. Localization of 5-HT1A receptors to astroglial cells in adult rats: implications for neuronal-glial interactions and psychoactive drug mechanism of action. Synapse 1993; 14: 201–5.PubMedGoogle Scholar
  127. Williams SM, Goldman-Rakic PS. Characterization of the dopaminergic innervation of the primate frontal cortex using a dopamine-specific antibody. Cereb Cortex 1993; 3: 199222.Google Scholar
  128. Willner P. Dopaminergic mechanisms in depression and mania. Psychopharmacology: The Fourth Generation of Progress (Bloom FE and Kupfer DJ eds), Raven Press, New York 1995; pp 921–931.Google Scholar
  129. Winsberg ME, Sachs N, Tate DL, Adalsteinsson E, Spielman D, Ketter TA. Decreased dorsolateral prefrontal N-acetyl aspartate in bipolar disorder. Biol Psychiatry 2000; 47: 475–81.PubMedGoogle Scholar
  130. Wolosker H, Blackshaw S, Snyder SH. Serine racemase: a glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission. Proc Natl Acad Sci USA 1999; 96: 13409–14.PubMedGoogle Scholar
  131. Zimmer DB, Cornwall EH, Landar A, Song W. The S 100 protein family history, function, and expression. Brain Res Bull 1995; 37: 417–29.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Grazyna Rajkowska

There are no affiliations available

Personalised recommendations