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Neuropathological changes in the nucleus basalis in schizophrenia

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Abstract

The nucleus basalis has not been examined in detail in severe mental illness. Several studies have demonstrated decreases in glia and glial markers in the cerebral cortex in schizophrenia, familial bipolar disorder and recurrent depression. Changes in neocortical neuron size and shape have also been reported. The nucleus basalis is a collection of large cholinergic neurons in the basal forebrain receiving information from the midbrain and limbic system, projecting to the cortex and involved with attention, learning and memory, and receives regulation from serotonergic inputs. Forty-one cases aged 41–60 years with schizophrenia or major depressive disorder with age-matched controls were collected. Formalin-fixed paraffin-embedded coronal nucleus basalis sections were histologically stained for oligodendrocyte identification with cresyl-haematoxylin counterstain, for neuroarchitecture with differentiated cresyl violet stain and astrocytes were detected by glial fibrillary acid protein immunohistochemistry. Cell density and neuroarchitecture were measured using Image Pro Plus. There were larger NB oval neuron soma in the combined schizophrenia and major depression disorder groups (p = 0.038), with no significant change between controls and schizophrenia and major depression disorder separately. There is a significant reduction in oligodendrocyte density (p = 0.038) in the nucleus basalis in schizophrenia. The ratio of gemistocytic to fibrillary astrocytes showed a greater proportion of the former in schizophrenia (18.1 %) and major depressive disorder (39.9 %) than in controls (7.9 %). These results suggest glial cell abnormalities in the nucleus basalis in schizophrenia possibly leading to cortical-limbic disturbance and subcortical dysfunction.

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References

  1. Aasen I, Kumari V, Sharma T (2005) Effects of rivastigmine on sustained attention in schizophrenia: an fMRI study. J Clin Psychopharmacol 25:311–317

    Article  PubMed  CAS  Google Scholar 

  2. Afifi M (2007) Gender differences in mental health. Singap Med J 48:385–391

    CAS  Google Scholar 

  3. Amunts VV (2007) Structural asymmetry of the basal nucleus of Meynert in men and women. Neurosci Behav Physiol 37:517–521

    Article  PubMed  CAS  Google Scholar 

  4. Bancher C, Paulus W, Paukner K, Jellinger K (1997) Neuropathologic diagnosis of Alzheimer disease: consensus between practicing neuropathologists? Alzheimer Dis Assoc Disord 11:207–219

    PubMed  CAS  Google Scholar 

  5. Bartus RT, Dean RL, Beer B 3rd, Lippa AS (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217:408–414

    Article  PubMed  CAS  Google Scholar 

  6. Benes FM, Lange N (2001) Two-dimensional versus three-dimensional cell counting: a practical perspective. Trends Neurosci 24:11–17

    Article  PubMed  CAS  Google Scholar 

  7. Bennett JP Jr, Enna SJ, Bylund DB, Gillin JC, Wyatt RJ, Snyder SH (1979) Neurotransmitter receptors in frontal cortex of schizophrenics. Arch Gen Psychiatry 36:927–934

    Article  PubMed  CAS  Google Scholar 

  8. Bilder RM, Wu H, Bogerts B, Degreef G, Ashtari M, Alvir JM, Snyder PJ, Lieberman JA (1994) Absence of regional hemispheric volume asymmetries in first-episode schizophrenia. Am J Psychiatry 151:1437–1447

    PubMed  CAS  Google Scholar 

  9. Bora E, Veznedaroglu B, Kayahan B (2005) The effect of galantamine added to clozapine on cognition of five patients with schizophrenia. Clin Neuropharmacol 28:139–141

    Article  PubMed  Google Scholar 

  10. Bushong EA, Martone ME, Ellisman MH (2004) Maturation of astrocyte morphology and the establishment of astrocyte domains during postnatal hippocampal development. Int J Dev Neurosci 22:73–86

    Article  PubMed  Google Scholar 

  11. Carnes KM, Fuller TA, Price JL (1990) Sources of presumptive glutamatergic/aspartatergic afferents to the magnocellular basal forebrain in the rat. J Comp Neurol 302:824–852

    Article  PubMed  CAS  Google Scholar 

  12. Chiba AA, Bucci DJ, Holland PC, Gallagher M (1995) Basal forebrain cholinergic lesions disrupt increments but not decrements in conditioned stimulus processing. J Neurosci Off J Soc Neurosci 15:7315–7322

    CAS  Google Scholar 

  13. Choi CY, Han SR, Yee GT, Lee CH (2010) A understanding of the temporal stem. J Korean Neurosurg Soc 47:365–369

    Article  PubMed  Google Scholar 

  14. Cotter DR, Pariante CM, Everall IP (2001) Glial cell abnormalities in major psychiatric disorders: the evidence and implications. Brain Res Bull 55:585–595

    Article  PubMed  CAS  Google Scholar 

  15. Cowell PE, Kostianovsky DJ, Gur RC, Turetsky BI, Gur RE (1996) Sex differences in neuroanatomical and clinical correlations in schizophrenia. Am J Psychiatry 153:799–805

    PubMed  CAS  Google Scholar 

  16. Crook JM, Dean B, Pavey G, Copolov D (1999) The binding of [3H]AFDX 384 is reduced in the caudate-putamen of subjects with schizophrenia. Life Sci 64:1761–1771

    Article  PubMed  CAS  Google Scholar 

  17. Crook JM, Tomaskovic-Crook E, Copolov DL, Dean B (2000) Decreased muscarinic receptor binding in subjects with schizophrenia: a study of the human hippocampal formation. Biol Psychiatry 48:381–388

    Article  PubMed  CAS  Google Scholar 

  18. Crook JM, Tomaskovic-Crook E, Copolov DL, Dean B (2000) Low muscarinic receptor binding in prefrontal cortex from subjects with schizophrenia: a study of Brodmann’s areas 8, 9, 10, and 46 and the effects of neuroleptic drug treatment. Am J Psychiatry 158:918–925

    Google Scholar 

  19. Cummings JL, Kaufer D (1996) Neuropsychiatric aspects of Alzheimer’s disease: the cholinergic hypothesis revisited. Neurology 47:876–883

    Article  PubMed  CAS  Google Scholar 

  20. Dean B, Crook JM, Opeskin K, Hill C, Keks N, Copolov DL (1996) The density of muscarinic M1 receptors is decreased in the caudate-putamen of subjects with schizophrenia. Mol Psychiatry 1:54–58

    PubMed  CAS  Google Scholar 

  21. Dean B, McLeod M, Keriakous D, McKenzie J, Scarr E (2002) Decreased muscarinic 1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia. Mol Psychiatry 7:1083–1091

    Article  PubMed  CAS  Google Scholar 

  22. Drevets WC, Gautier C, Price JC, Kupfer DJ, Kinahan PE, Grace AA, Price JL, Mathis CA (2001) Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria. Biol Psychiatry 49:81–96

    Article  PubMed  CAS  Google Scholar 

  23. Emsley JG, Macklis JD (2006) Astroglial heterogeneity closely reflects the neuronal-defined anatomy of the adult murine CNS. Neuron Glia Biol 2:175–186

    Article  PubMed  Google Scholar 

  24. Erickson SK, Schwarzkopf SB, Palumbo D, Badgley-Fleeman J, Smirnow AM, Light GA (2005) Efficacy and tolerability of low-dose donepezil in schizophrenia. Clin Neuropharmacol 28:179–184

    Article  PubMed  CAS  Google Scholar 

  25. Falkai P, Honer WG, David S, Bogerts B, Majtenyi C, Bayer TA (1999) No evidence for astrogliosis in brains of schizophrenic patients. A post-mortem study. Neuropathol Appl Neurobiol 25:48–53

    Article  PubMed  CAS  Google Scholar 

  26. Fellner L, Jellinger KA, Wenning GK, Stefanova N (2011) Glial dysfunction in the pathogenesis of α-synucleinopathies: emerging concepts. Acta Neuropathol 121:675–693

    Article  PubMed  CAS  Google Scholar 

  27. Freudenreich O, Herz L, Deckersbach T, Evins AE, Henderson DC, Cather C, Goff DC (2005) Added donepezil for stable schizophrenia: a double-blind, placebo-controlled trial. Psychopharmacology (Berlin) 181:358–363

    Article  CAS  Google Scholar 

  28. Gasbarri A, Sulli A, Pacitti C, McGaugh JL (1999) Serotonergic input to cholinergic neurons in the substantia innominata and nucleus basalis magnocellularis in the rat. Neuroscience 91:1129–1142

    Article  PubMed  CAS  Google Scholar 

  29. Guest PC, Schwarz E, Krishnamurthy D, Harris LW, Leweke FM, Rothermundt M, van Beveren NJ, Spain M, Barnes A, Steiner J, Rahmoune H, Bahn S (2011) Altered levels of circulating insulin and other neuroendocrine hormones associated with the onset of schizophrenia. Psychoneuroendocrinology 36:1092–1096

    Article  PubMed  CAS  Google Scholar 

  30. Hafner H, Maurer K, Loffler W, Riecher-Rossler A (1993) The influence of age and sex on the onset and early course of schizophrenia. Brit J Psychiatry J Mental Sci 162:80–86

    Article  CAS  Google Scholar 

  31. Hakak Y, Walker JR, Li C, Wong WH, Davis KL, Buxbaum JD, Haroutunian V, Fienberg AA (2001) Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc Natl Acad Sci USA 98:4746–4751

    Article  PubMed  CAS  Google Scholar 

  32. Hamidi M, Drevets WC, Price JL (2004) Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes. Biol Psychiatry 55:563–569

    Article  PubMed  Google Scholar 

  33. Harrison PJ (1999) The neuropathological effects of antipsychotic drugs. Schizophr Res 40:87–99

    Article  PubMed  CAS  Google Scholar 

  34. Heimer L (2000) Basal forebrain in the context of schizophrenia. Brain Res Rev 31:205–235

    Article  PubMed  CAS  Google Scholar 

  35. Hof PR, Haroutunian V, Friedrich VL Jr, Byne W, Buitron C, Perl DP, Davis KL (2003) Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia. Biol Psychiatry 53:1075–1085

    Article  PubMed  CAS  Google Scholar 

  36. Hutchinson M, Fazzini E (1996) Cholinesterase inhibition in Parkinson’s disease. J Neurol Neurosurg Psychiatry 61:324–325

    Article  PubMed  CAS  Google Scholar 

  37. Ishibashi T, Dakin KA, Stevens B, Lee PR, Kozlov SV, Stewart CL, Fields RD (2006) Astrocytes promote myelination in response to electrical impulses. Neuron 49:823–832

    Article  PubMed  CAS  Google Scholar 

  38. Jellinger KA (2009) Lewy body/alpha-synucleinopathy in schizophrenia and depression: a preliminary neuropathological study. Acta Neuropathol 117:423–427

    Article  PubMed  CAS  Google Scholar 

  39. Johnston-Wilson NL, Sims CD, Hofmann JP, Anderson L, Shore AD, Torrey EF, Yolken RH (2000) Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. Stanley Neuropathol Consortium Mol Psychiatry 5:142–149

    CAS  Google Scholar 

  40. Jones BE, Cuello AC (1989) Afferents to the basal forebrain cholinergic cell area from pontomesencephalic–catecholamine, serotonin, and acetylcholine–neurons. Neuroscience 31:37–61

    Article  PubMed  CAS  Google Scholar 

  41. Jones EG, Burton H, Saper CB, Swanson LW (1976) Midbrain, diencephalic and cortical relationships of the basal nucleus of Meynert and associated structures in primates. J Comp Neurol 167:385–419

    Article  PubMed  CAS  Google Scholar 

  42. Kasper BS, Taylor DC, Janz D, Kasper EM, Maier M, Williams MR, Crow TJ (2010) Neuropathology of epilepsy and psychosis: the contributions of J.A.N. Corsellis Brain 133:3795–3805

    Article  Google Scholar 

  43. Katerina Z, Andrew K, Filomena M, Xu-Feng H (2004) Investigation of m1/m4 muscarinic receptors in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression disorder. Neuropsychopharmacology 29:619–625

    Article  PubMed  CAS  Google Scholar 

  44. Laming PR (2000) Potassium signalling in the brain: its role in behaviour. Neurochem Int 36:271–290

    Article  PubMed  CAS  Google Scholar 

  45. Lara DR, Gama CS, Belmonte-de-Abreu P, Portela LV, Goncalves CA, Fonseca M, Hauck S, Souza DO (2001) Increased serum S100B protein in schizophrenia: a study in medication-free patients. J Psychiatr Res 35:11–14

    Article  PubMed  CAS  Google Scholar 

  46. Lenzi A, Maltinti E, Poggi E, Fabrizio L, Coli E (2003) Effects of rivastigmine on cognitive function and quality of life in patients with schizophrenia. Clin Neuropharmacol 26:317–321

    Article  PubMed  CAS  Google Scholar 

  47. Lim KO, Hedehus M, Moseley M, de Crespigny A, Sullivan EV, Pfefferbaum A (1999) Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging. Arch Gen Psychiatry 56:367–374

    Article  PubMed  CAS  Google Scholar 

  48. Mai J, Assheuer J, Paxinos G (2004) Atlas of the human brain, 2nd edn. Elsevier publishing, Amsterdam

    Google Scholar 

  49. Mattsson A, Olson L, Svensson TH, Schilström B (2007) Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in the accumbens but not striatum. Exp Neurol 208:73–79

    Article  PubMed  CAS  Google Scholar 

  50. Mesulam MM, Mufson EJ (1984) Neural inputs into the nucleus basalis of the substantia innominata (Ch4) in the rhesus monkey. Brain A J Neurol 107:253–274

    Article  Google Scholar 

  51. Mesulam MM, Mufson EJ, Levey AI, Wainer BH (1983) Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol 214:170–197

    Article  PubMed  CAS  Google Scholar 

  52. Miller R, Chouinard G (1993) Loss of striatal cholinergic neurons as a basis for tardive and L-dopa-induced dyskinesias, neuroleptic-induced supersensitivity psychosis and refractory schizophrenia. Biol Psychiatry 34:713–738

    Article  PubMed  CAS  Google Scholar 

  53. Moises HW, Zoega T, Gottesman II (2002) The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia. BMC Psychiatry 2:8

    Article  PubMed  Google Scholar 

  54. Pakkenberg B (1990) Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. Arch Gen Psychiatry 47:1023–1028

    Article  PubMed  CAS  Google Scholar 

  55. Pariante CM, Pearce BD, Pisell TL, Owens MJ, Miller AH (1997) Steroid-independent translocation of the glucocorticoid receptor by the antidepressant desipramine. Mol Pharmacol 52:571–581

    PubMed  CAS  Google Scholar 

  56. Perry EK, Marshall E, Perry RH, Irving D, Smith CJ, Blessed G, Fairbairn AF (1990) Cholinergic and dopaminergic activities in senile dementia of Lewy body type. Alzheimer Dis Assoc Disord 4:87–95

    PubMed  CAS  Google Scholar 

  57. Pinto T, Lanctôt KL, Herrmann N (2011) Revisiting the cholinergic hypothesis of behavioral and psychological symptoms in dementia of the Alzheimer’s Type. Ageing Res Rev 10:404–412

    PubMed  CAS  Google Scholar 

  58. Raedler TJ, Knable MB, Jones DW, Urbina RA, Gorey JG, Lee KS, Egan MF, Coppola R, Weinberger DR (2003) In vivo determination of muscarinic acetylcholine receptor availability in schizophrenia. Am J Psychiatry 160:118–127

    Article  PubMed  Google Scholar 

  59. Rajkowska G, Miguel-Hidalgo JJ, Makkos Z, Meltzer H, Overholser J, Stockmeier C (2002) Layer-specific reductions in GFAP-reactive astroglia in the dorsolateral prefrontal cortex in schizophrenia. Schizophr Res 57:127–138

    Article  PubMed  Google Scholar 

  60. Rao TS, Correa LD, Adams P, Santori EM, Sacaan AI (2003) Pharmacological characterization of dopamine, norepinephrine and serotonin release in the rat prefrontal cortex by neuronal nicotinic acetylcholine receptor agonists. Brain Res 990:203–208

    Article  PubMed  CAS  Google Scholar 

  61. Rasmusson DD, Szerb IC, Jordan JL (1996) Differential effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate receptor antagonists applied to the basal forebrain on cortical acetylcholine release and electroencephalogram desynchronization. Neuroscience 72:419–427

    Article  PubMed  CAS  Google Scholar 

  62. Rothermundt M, Missler U, Arolt V, Peters M, Leadbeater J, Wiesmann M, Rudolf S, Wandinger KP, Kirchner H (2001) Increased S100B blood levels in unmedicated and treated schizophrenic patients are correlated with negative symptomatology. Mol Psychiatry 6:445–449

    Article  PubMed  CAS  Google Scholar 

  63. Satoh J, Tabunoki H, Yamamura T, Arima K, Konno H (2007) Human astrocytes express aquaporin-1 and aquaporin-4 in vitro and in vivo. Neuropathol Off J Jpn Soc Neuropathol 27:245–256

    Article  Google Scholar 

  64. Schmitt A, Steyskal C, Bernstein HG, Schneider-Axmann T, Parlapani E, Schaeffer EL, Gattaz WF, Bogerts B, Schmitz C, Falkai P (2009) Stereologic investigation of the posterior part of the hippocampus in schizophrenia. Acta Neuropathol 117:395–407

    Article  PubMed  Google Scholar 

  65. Sinclair D, Tsai SY, Woon HG, Weickert CS (2011) Abnormal glucocorticoid receptor mRNA and protein isoform expression in the prefrontal cortex in psychiatric illness. Neuropsychopharmacology 36:2698–2709

    Article  PubMed  CAS  Google Scholar 

  66. Smiley JF, Mesulam MM (1999) Cholinergic neurons of the nucleus basalis of Meynert receive cholinergic, catecholaminergic and GABAergic synapses: an electron microscopic investigation in the monkey. Neuroscience 88:241–255

    Article  PubMed  CAS  Google Scholar 

  67. Stark AK, Uylings HB, Sanz-Arigita E, Pakkenberg B (2004) Glial cell loss in the anterior cingulate cortex, a subregion of the prefrontal cortex, in subjects with schizophrenia. Am J Psychiatry 161:882–888

    Article  PubMed  Google Scholar 

  68. Steiner J, Bernstein HG, Bielau H, Farkas N, Winter J, Dobrowolny H, Brisch R, Gos T, Mawrin C, Myint AM, Bogerts B (2008) S100B-immunopositive glia is elevated in paranoid as compared to residual schizophrenia: a morphometric study. J Psychiatr Res 42:868–876

    Article  PubMed  Google Scholar 

  69. Steriade M, Parent A, Pare D, Smith Y (1987) Cholinergic and non-cholinergic neurons of cat basal forebrain project to reticular and mediodorsal thalamic nuclei. Brain Res 408:372–376

    Article  PubMed  CAS  Google Scholar 

  70. Stoehr JD, Mobley SL, Roice D, Brooks R, Baker LM, Wiley RG, Wenk GL (1997) The effects of selective cholinergic basal forebrain lesions and aging upon expectancy in the rat. Neurobiol Learn Mem 67:214–227

    Article  PubMed  CAS  Google Scholar 

  71. Stryer R, Strous R, Bar F, Shaked G, Shiloh R, Rozencwaig S, Grupper D, Buchman N, Kotler M, Rabey JM, Weizman A (2004) Donepezil augmentation of clozapine monotherapy in schizophrenia patients: a double blind cross-over study. Hum Psychopharmacol 19:343–346

    Article  Google Scholar 

  72. Stryer R, Strous RD, Bar F, Werber E, Shaked G, Buhiri Y et al (2003) Beneficial effect of donepezil augmentation for the management of comorbid schizophrenia and dementia. Clin Neuropharmacol 26:12–17

    Article  Google Scholar 

  73. Sugai T, Kawamura M, Iritani S, Araki K, Makifuchi T, Imai C, Nakamura R, Kakita A, Takahashi H, Nawa H (2004) Prefrontal abnormality of schizophrenia revealed by DNA microarray: impact on glial and neurotrophic gene expression. Ann N Y Acad Sci 1025:84–91

    Article  PubMed  CAS  Google Scholar 

  74. Tugal O, Yazici KM, Yagcioglu AE, Gogus A (2004) A double-blind, placebo controlled, cross-over trial of adjunctive donepezil for cognitive impairment in schizophrenia. Int J Neuropsychopharmacol 7:117–123

    Article  PubMed  CAS  Google Scholar 

  75. Uranova NA, Vostrikov VM, Vikhreva OV, Zimina IS, Kolomeets NS, Orlovskaya DD (2007) The role of oligodendrocyte pathology in schizophrenia. Int J Neuropsychopharmacol 10:537–545

    Article  PubMed  CAS  Google Scholar 

  76. Uranova NA, Vostrikov VM, Orlovskaya DD, Rachmanova VI (2004) Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley neuropathology consortium. Schizophr Res 67:269–275

    Article  PubMed  Google Scholar 

  77. van Haren NE, Schnack HG, Cahn W, van den Heuvel MP, Lepage C, Collins L, Evans AC, Hulshoff Pol HE, Kahn RS (2011) Changes in cortical thickness during the course of illness in schizophrenia. Arch Gen Psychiatry 68:871–880

    Article  PubMed  Google Scholar 

  78. Virgin CE Jr, Ha TP, Packan DR, Tombaugh GC, Yang SH, Horner HC, Sapolsky RM (1991) Glucocorticoids inhibit glucose transport and glutamate uptake in hippocampal astrocytes: implications for glucocorticoid neurotoxicity. J Neurochem 57:1422–1428

    Article  PubMed  CAS  Google Scholar 

  79. Watanabe S, Nishikawa T, Takashima M, Toru M (1983) Increased muscarinic cholinergic receptors in prefrontal cortices of medicated schizophrenics. Life Sci 33:2187–2196

    Article  PubMed  CAS  Google Scholar 

  80. Webster MJ, Knable MB, Johnston-Wilson N, Nagata K, Inagaki M, Yolken RH (2001) Immunohistochemical localization of phosphorylated glial fibrillary acidic protein in the prefrontal cortex and hippocampus from patients with schizophrenia, bipolar disorder, and depression. Brain Behav Immun 15:388–400

    Article  PubMed  CAS  Google Scholar 

  81. Webster MJ, O’Grady J, Kleinman JE, Weickert CS (2005) Glial fibrillary acidic protein mRNA levels in the cingulate cortex of individuals with depression, bipolar disorder and schizophrenia. Neuroscience 133:453–461

    Article  PubMed  CAS  Google Scholar 

  82. Wenk GL (1997) The nucleus basalis magnocellularis cholinergic system: one hundred years of progress. Neurobiol Learn Mem 67:85–95

    Article  PubMed  CAS  Google Scholar 

  83. Whitehouse PJ, Hedreen JC, White CL, Price DL (1983) Basal forebrain neurons in the dementia of Parkinson disease. Ann Neurol 13:243–248

    Article  PubMed  CAS  Google Scholar 

  84. Whitehouse PJ, Price DL, Clark AW, Coyle JT, DeLong MR (1981) Alzheimer’s disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 10:122–126

    Article  PubMed  CAS  Google Scholar 

  85. Williams MR, Chaudhry R, Perera S, Pearce RKB, Hirsch SR, Ansorge O, Thom M, Maier M (2012a). Changes in cortical thickness in the frontal lobes in schizophrenia are a result of thinning of pyramidal cell layers. Eur Arch Psychiatry Clin Neurosci (May 19th Epub)

  86. Williams MR, Hampton T, Pearce RKB, Hirsch SR, Ansorge O, Thom M, Maier M (2012b) Astrocyte decrease in the subgenual cingulate and callosal genu in schizophrenia. Eur Arch Psychiatry Clin Neurosci (June 4th Epub)

  87. Williams MR, Pearce RKB, Hirsch SR, Ansorge O, Thom M, Maier M (2006) Astrocytes abnormalities differentiate schizophrenia from affective disorders in post-mortem brain. Schizophr Res 81(supp):72

    Google Scholar 

  88. Zaborszky L, Cullinan WE (1992) Projections from the nucleus accumbens to cholinergic neurons of the ventral pallidum: a correlated light and electron microscopic double-immunolabeling study in rat. Brain Res 570:92–101

    Article  PubMed  CAS  Google Scholar 

  89. Zaborszky L, Gaykema RP, Swanson DJ, Cullinan WE (1997) Cortical input to the basal forebrain. Neuroscience 79:1051–1078

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Dr. Federico Roncaroli for aid with dissection and Prof. Federico Turkheimer for advice on statistics. This work was funded by the Stanley foundation and MRC-UK PET Methodology Programme Grant G1100809/1. The tissue was obtained from the Corsellis collection, which is supported by the Starr foundation and the West London Mental Health Trust.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. King’s College London, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK

    M. R. Williams

  2. Neuropathology Unit, Department of Medicine, Imperial College London, Charing Cross Hospital, Charing Cross Campus, London, W6 8RF, UK

    M. R. Williams, R. Marsh, R. K. B. Pearce, S. R. Hirsch & S. M. Gentleman

  3. Academic Neurosurgery Unit, St. George’s, University of London, London, UK

    C. D. Macdonald

  4. Department of Biology, Johns Hopkins University, 3400N. Charles St., Baltimore, MD, 21218, USA

    J. Jain

  5. Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK

    J. Jain

  6. Department of Neuropathology, The Radcliffe Infirmary, Oxford, OX2 6HE, UK

    O. Ansorge

  7. Trust HQ, West London Mental Health NHS Trust, Southall, Middlesex, UB1 3EU, UK

    M. Maier

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Williams, M.R., Marsh, R., Macdonald, C.D. et al. Neuropathological changes in the nucleus basalis in schizophrenia. Eur Arch Psychiatry Clin Neurosci 263, 485–495 (2013). https://doi.org/10.1007/s00406-012-0387-7

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