Schizophrenia Research
Volume 93, Issue 1 , Pages 13-22 , July 2007

Differential effects of typical and atypical antipsychotics on brain myelination in schizophrenia

  • George Bartzokis

      Affiliations

    • Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
    • Laboratory of Neuroimaging, Department of Neurology, Division of Brain Mapping, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
    • Greater Los Angeles VA Healthcare System, West Los Angeles, CA, 90073, United States
    • Brain Research Institute, UCLA, Los Angeles, CA 90095, United States
    • Corresponding Author InformationCorresponding author. UCLA Alzheimer's Disease Center, 710 Westwood Plaza, Room 2-238, Los Angeles, CA 90095-1769, United States. Tel.: +1 310 206 3207; fax: +1 310 268 3266.
    • ,
  • Po H. Lu

      Affiliations

    • Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
    • Greater Los Angeles VA Healthcare System, West Los Angeles, CA, 90073, United States
    • ,
  • Keith H. Nuechterlein

      Affiliations

    • Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
    • Department of Psychology, UCLA, Los Angeles, CA 90095, United States
    • ,
  • Michael Gitlin

      Affiliations

    • Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
    • ,
  • Clarissa Doi

      Affiliations

    • Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
    • Greater Los Angeles VA Healthcare System, West Los Angeles, CA, 90073, United States
    • ,
  • Nancy Edwards

      Affiliations

    • Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
    • Greater Los Angeles VA Healthcare System, West Los Angeles, CA, 90073, United States
    • ,
  • Christopher Lieu

      Affiliations

    • Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
    • Greater Los Angeles VA Healthcare System, West Los Angeles, CA, 90073, United States
    • ,
  • Lori L. Altshuler

      Affiliations

    • Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
    • Department of Psychology, UCLA, Los Angeles, CA 90095, United States
    • ,
  • Jim Mintz

      Affiliations

    • Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States

Received 28 September 2006 ,Revised 14 February 2007 ,Accepted 16 February 2007.

References 

  1. Allen JS, Bruss J, Brown CK, Damasio H. Normal neuroanatomical variation due to age: the major lobes and a parcellation of the temporal region. Neurobiol. Aging. 2005;26:1245–1260
  2. Ardekani BA, Nierenberg J, Hoptman MJ, Javitt DC, Lim KO. MRI study of white matter diffusion anisotropy in schizophrenia. NeuroReport. 2003;14:2025–2029
  3. Ardekani BA, Bappal A, D'Angelo D, Ashtari M, Lencz T, Szeszko PR, et al. Brain morphometry using diffusion-weighted magnetic resonance imaging: application to schizophrenia. NeuroReport. 2005;16:1455–1459
  4. Aston C, Jiang L, Sokolov BP. Microarray analysis of postmortem temporal cortex from patients with schizophrenia. J. Neurosci. Res. 2004;77:858–866
  5. Aston C, Jiang L, Sokolov BP. Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder. Mol. Psychiatry. 2005;10:309–322
  6. Barch DM, Carter CS. Amphetamine improves cognitive function in medicated individuals with schizophrenia and in healthy volunteers. Schizophr. Res. 2005;77:43–58
  7. Barkovich AJ, Lyon G, Evrard P. Formation, maturation, and disorders of white matter. AJNR. Am. J. Neuroradiol. 1992;13:447–461
  8. Bartzokis G. Schizophrenia: breakdown in the well-regulated lifelong process of brain development and maturation. Neuropsychopharmacology. 2002;27:672–683
  9. Bartzokis G. Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer's disease. Neurobiol. Aging. 2004;25:5–18
  10. Bartzokis G. Quadratic trajectories of brain myelin content: unifying construct for neuropsychiatric disorders. Neurobiol. Aging. 2004;25:49–62
  11. Bartzokis G. Brain myelination in prevalent neuropsychiatric developmental disorders: primary and comorbid addiction. Adolesc. Psych. 2005;29:55–96
  12. Bartzokis G, Altshuler LL. Biological underpinnings of treatment resistance in schizophrenia: a hypothesis. Psychopharmacol. Bull. 2003;37:5–7
  13. Bartzokis G, Altshuler L. Reduced intracortical myelination in schizophrenia. Am. J. Psychiatry. 2005;162:1229–1230
  14. Bartzokis G, Mintz J, Marx P, Osborn D, Gutkind D, Chiang F, et al. Reliability of in vivo volume measures of hippocampus and other brain structures using MRI. Magn. Reson. Imaging. 1993;11:993–1006
  15. Bartzokis G, Beckson M, Lu PH, Nuechterlein KH, Edwards N, Mintz J. Age-related changes in frontal and temporal lobe volumes in men: a magnetic resonance imaging study. Arch. Gen. Psychiatry. 2001;58:461–465
  16. Bartzokis G, Nuechterlein KH, Lu PH, Gitlin M, Rogers S, Mintz J. Dysregulated brain development in adult men with schizophrenia: a magnetic resonance imaging study. Biol. Psychiatry. 2003;53:412–421
  17. Bartzokis G, Sultzer D, Lu PH, Nuechterlein KH, Mintz J, Cummings J. Heterogeneous age-related breakdown of white matter structural integrity: implications for cortical “disconnection” in aging and Alzheimer's disease. Neurobiol. Aging. 2004;25:843–851
  18. Bartzokis G, Lu PH, Turner J, Mintz J, Saunders CS. Adjunctive risperidone in the treatment of chronic combat-related posttraumatic stress disorder. Biol. Psychiatry. 2005;57:474–479
  19. Beasley CL, Honer WG, Bergmann K, Falkai P, Lutjohann D, Bayer TA. Reductions in cholesterol and synaptic markers in association cortex in mood disorders. Bipolar Disord. 2005;7:449–455
  20. Belachew S, Rogister B, Rigo JM, Malgrange B, Moonen G. Neurotransmitter-mediated regulation of CNS myelination: a review. Acta Neurol. Belg. 1999;99:21–31
  21. Benes FM, Turtle M, Khan Y, Farol P. Myelination of a key relay zone in the hippocampal formation occurs in the human brain during childhood, adolescence, and adulthood. Arch. Gen. Psychiatry. 1994;51:477–484
  22. Braga RJ, Petrides G. The combined use of electroconvulsive therapy and antipsychotics in patients with schizophrenia. J. ECT. 2005;21:75–83
  23. Cahir M, Costello I, King DJ, Reynolds GP. Chronic haloperidol or clozapine treatment does not alter parvalbumin immunoreactivity in the rat frontal cortex or hippocampus. Neurosci. Lett. 2005;373:57–60
  24. Chambers JS, Perrone-Bizzozero NI. Altered myelination of the hippocampal formation in subjects with schizophrenia and bipolar disorder. Neurochem. Res. 2004;29:2293–2302
  25. Cotter D, Mackay D, Chana G, Beasley C, Landau S, Everall IP. Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder. Cereb. Cortex. 2002;12:386–394
  26. Eltayb A, Wadenberg ML, Svensson TH. Enhanced cortical dopamine output and antipsychotic-like effect of raclopride with adjunctive low-dose l-dopa. Biol. Psychiatry. 2005;58:337–343
  27. Ferno J, Raeder MB, Vik-Mo AO, Skrede S, Glambek M, Tronstad KJ, et al. Antipsychotic drugs activate SREBP-regulated expression of lipid biosynthetic genes in cultured human glioma cells: a novel mechanism of action?. Pharmacogenomics J. 2005;5:298–304
  28. Flynn SW, Lang DJ, Mackay AL, Goghari V, Vavasour IM, Whittall KP, et al. Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins. Mol. Psychiatry. 2003;8:811–820
  29. Garver DL, Holcomb JA, Christensen JD. Cerebral cortical gray expansion associated with two second-generation antipsychotics. Biol. Psychiatry. 2005;58:62–66
  30. Ge Y, Grossman RI, Babb JS, Rabin ML, Mannon LJ, Kolson DL. Age-related total gray matter and white matter changes in normal adult brain. Part I: Volumetric MR Imaging Analysis. AJNR. Am. J. Neuroradiol. 2002;23:1327–1333
  31. Hakak Y, Walker JR, Li C, Wong WH, Davis KL, Buxbaum JD, et al. Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. PNAS. 2001;98:4746–4751
  32. Hamidi M, Drevets WC, Price JL. Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes. Biol. Psychiatry. 2004;55:563–569
  33. Harvey PD, Green MF, McGurk SR, Meltzer HY. Changes in cognitive functioning with risperidone and olanzapine treatment: a large-scale, double-blind, randomized study. Psychopharmacology (Berl). 2003;169:404–411
  34. Ho BC, Andreasen NC, Nopoulos P, Arndt S, Magnotta V, Flaum M. Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia. Arch. Gen. Psychiatry. 2003;60:585–594
  35. Hof PR, Haroutunian V, Copland C, Davis KL, Buxbaum JD. Molecular and cellular evidence for an oligodendrocyte abnormality in schizophrenia. Neurochem. Res. 2002;27:1193–1200
  36. Hof PR, Haroutunian V, Friedrich VL, Byne W, Buitron C, Perl DP, et al. Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia. Biol. Psychiatry. 2003;53:1075–1085
  37. Jernigan TL, Gamst AC. Changes in volume with age-consistency and interpretation of observed effects. Neurobiol. Aging. 2005;26:1271–1274
  38. Kaes T. Die Grosshirnrinde des Menschen in ihren Massen und in ihrem Fasergehalt. Jena: Gustav Fisher; 1907;
  39. Kanaan RA, Kim JS, Kaufmann WE, Pearlson GD, Barker GJ, McGuire PK. Diffusion tensor imaging in schizophrenia. Biol. Psychiatry. 2005;58:921–929
  40. Kemper T. Neuroanatomical and neuropathological changes during aging and dementia. In:  Albert M,  Knoefel J editor. Clinical Neurology of Aging. 2nd ed.. New York: Oxford University Press; 1994;p. 3–67
  41. Kodama M, Fujioka T, Duman RS. Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat. Biol. Psychiatry. 2004;56:570–580
  42. Koenig SH. Cholesterol of myelin is the determinant of gray–white contrast in MRI of brain. Magn. Reson. Med. 1991;20:285–291
  43. Kubicki M, Park H, Westin CF, Nestor PG, Mulkern RV, Maier SE, et al. DTI and MTR abnormalities in schizophrenia: analysis of white matter integrity. NeuroImage. 2005;26:1109–1118
  44. Li T, Stefansson H, Gudfinnsson E, Cai G, Liu X, Murray RM, et al. Identification of a novel neuregulin 1 at-risk haplotype in Han schizophrenia Chinese patients, but no association with the Icelandic/Scottish risk haplotype. Mol. Psychiatry. 2004;1–7
  45. Li Z, Ichikawa J, Huang M, Prus AJ, Dai J, Meltzer HY. ACP-103, a 5-HT(2A/2C) inverse agonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens. Psychopharmacology (Berl). 2005;183:144–153
  46. Lieberman J, Chakos M, Wu H, Alvir J, Hoffman E, Robinson D, et al. Longitudinal study of brain morphology in first episode schizophrenia. Biol. Psychiatry. 2001;49:487–499
  47. Lieberman JA, Tollefson GD, Charles C, Zipursky R, Sharma T, Kahn RS, et al. Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch. Gen. Psychiatry. 2005;62:361–370
  48. Liu CM, Hwu HG, Fann CS, Lin CY, Liu YL, Ou-Yang WC, et al. Linkage evidence of schizophrenia to loci near neuregulin 1 gene on chromosome 8p21 in Taiwanese families. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2005;134:79–83
  49. Lu A, Leow AD, Lee AD, Gogtay N, Rapoport JL, Toga AW, et al. Growth pattern abnormalities in childhood-onset schizophrenia visualized using tensor-based morphometry. In: 12th Annual Meeting of the Organization for Human Brain Mapping (OHBM), Florence, Italy, June 11–15, 2006. 2006;
  50. Madsen TM, Yeh DD, Valentine GW, Duman RS. Electroconvulsive seizure treatment increases cell proliferation in rat frontal cortex. Neuropsychopharmacology. 2005;30:27–34
  51. Marner L, Pakkenberg B. Total length of nerve fibers in prefrontal and global white matter of chronic schizophrenics. J. Psychiatr. Res. 2003;37:539–547
  52. McCormick L, Decker L, Nopoulos P, Ho BC, Andreasen N. Effects of atypical and typical neuroleptics on anterior cingulate volume in schizophrenia. Schizophr. Res. 2005;80:73–84
  53. McDonald C, Bullmore ET, Sham PC, Chitnis X, Wickham H, Bramon E, et al. Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes. Arch. Gen. Psychiatry. 2004;61:974–984
  54. Michailov GV, Sereda MW, Brinkmann BG, Fischer TM, Haug B, Birchmeier C, et al. Axonal neuregulin-1 regulates myelin sheath thickness. Science. 2004;304:700–703
  55. Miller AK, Alston RL, Corsellis JA. Variation with age in the volumes of grey and white matter in the cerebral hemispheres of man: measurements with an image analyser. Neuropathol. Appl. Neurobiol. 1980;6:119–132
  56. Molina V, Reig S, Sanz J, Palomo T, Benito C, Sanchez J, et al. Increase in gray matter and decrease in white matter volumes in the cortex during treatment with atypical neuroleptics in schizophrenia. Schizophr. Res. 2005;80:61–71
  57. Mori K, Nagao M, Yamashita H, Morinobu S, Yamawaki S. Effect of switching to atypical antipsychotics on memory in patients with chronic schizophrenia. Prog. Neuro-Psychopharmacol. Biol. Psychiatry. 2004;28:659–665
  58. Nuechterlein KH, Dawson ME, Ventura J, Gitlin M, Subotnik KL, Snyder KS, et al. The vulnerability/stress model of schizophrenic relapse: a longitudinal study. Acta Psychiatr. Scand., Suppl. 1994;382:58–64
  59. Nuechterlein KH, Subotnik KL, Gitlin MJ, Siegel BV, Bartzokis G, Fogelson DL, et al. Functional and cognitive outcome of first episode psychosis patients treated with fluphenazine decanoate or risperidone. In: American College of Neuropsychopharmacology 39th Annual Meeting. San Juan, Puerto Rico. Abstracts of Panels and Posters. vol. 56:2001;
  60. O'Brien JS, Sampson EL. Lipid composition of the normal human brain: gray matter, white matter, and myelin. J. Lipid Res. 1965;6:537–544
  61. Peirce TR, Bray NJ, Williams NM, Norton N, Moskvina V, Preece A, et al. Convergent evidence for 2′,3′-cyclic nucleotide 3′-phosphodiesterase as a possible susceptibility gene for schizophrenia. Arch. Gen. Psychiatry. 2006;63:18–24
  62. Rosin C, Colombo S, Calver AA, Bates TE, Skaper SD. Dopamine D2 and D3 receptor agonists limit oligodendrocyte injury caused by glutamate oxidative stress and oxygen/glucose deprivation. Glia. 2005;52:336–343
  63. Rouser G, Kritchevsky G, Yamamoto A, Baxter CF. Lipids in the nervous system of different species as a function of age: brain, spinal cord, peripheral nerve, purified whole cell preparations, and subcellular particulates: regulatory mechanisms and membrane structure. Adv. Lipid Res. 1972;10:261–360
  64. Schmitt A, Wilczek K, Blennow K, Maras A, Jatzko A, Petroianu G, et al. Altered thalamic membrane phospholipids in schizophrenia: a postmortem study. Biol. Psychiatry. 2004;56:41–45
  65. Selemon LD, Goldman-Rakic PS. The reduced neuropil hypothesis: a circuit based model of schizophrenia. Biol. Psychiatry. 1999;45:17–25
  66. 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(discussion 819–20)
  67. 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;46:161–172
  68. Selemon LD, Mrzljak J, Kleinman JE, Herman MM, Goldman-Rakic PS. Regional specificity in the neuropathologic substrates of schizophrenia: a morphometric analysis of Broca's area 44 and area 9. Arch. Gen. Psychiatry. 2003;60:69–77
  69. Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW. Mapping cortical change across the human life span. Nat. Neurosci. 2003;6:309–315
  70. Spencer KM, Nestor PG, Perlmutter R, Niznikiewicz MA, Klump MC, Frumin M, et al. Neural synchrony indexes disordered perception and cognition in schizophrenia. Proc. Natl. Acad Sci. U. S. A. 2004;101:17288–17293
  71. Stark AK, Uylings HB, Sanz-Arigita E, Pakkenberg B. Glial cell loss in the anterior cingulate cortex, a subregion of the prefrontal cortex, in subjects with schizophrenia. Am. J. Psychiatry. 2004;161:882–888
  72. Stefansson H, Sarginson J, Kong A, Yates P, Steinthorsdottir V, Gudfinnsson E, et al. Association of neuregulin 1 with schizophrenia confirmed in a Scottish population. Am. J. Hum. Genet. 2003;72:83–87
  73. Szeszko PR, Ardekani BA, Ashtari M, Kumra S, Robinson DG, Sevy S, et al. White matter abnormalities in first-episode schizophrenia or schizoaffective disorder: a diffusion tensor imaging study. Am. J. Psychiatry. 2005;162:602–605
  74. Tkachev D, Mimmack ML, Ryan MM, Wayland M, Freeman T, Jones PB, et al. Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet. 2003;362:798–805
  75. Tosato S, Dazzan P, Collier D. Association between the neuregulin 1 gene and schizophrenia: a systematic review. Schizophr. Bull. 2005;31:613–617
  76. Uranova NA, Vostrikov VM, Orlovskaya DD, Rachmanova VI. Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium. Schizophr. Res. 2004;67:269–275
  77. Uranova N, Vostrikov V, Vichreva O, Zimina I. Oligodendroglia in schizophrenia: findings from postmortem studies. In: World Federation of Societies of Biological Psychiatry, 8th World Congress of Biological Psychiatry. vol. 6:Vienna, Austria: The World Journal of Biological Psych; 2005;p. 74;supplement 1
  78. Valk J, van der Knaap MS. Magnetic Resonance of Myelin, Myelination, and Myelin Disorders. New York: Spring-Verlag; 1989;
  79. van der Knaap MS, Valk J. MR imaging of the various stages of normal myelination during the first year of life. Neuroradiology. 1990;31:459–470
  80. van der Stelt O, Frye J, Lieberman JA, Belger A. Impaired P3 generation reflects high-level and progressive neurocognitive dysfunction in schizophrenia. Arch. Gen. Psychiatry. 2004;61:237–248
  81. Van Kampen JM, Hagg T, Robertson HA. Induction of neurogenesis in the adult rat subventricular zone and neostriatum following dopamine D receptor stimulation. Eur. J. Neurosci. 2004;19:2377–2387
  82. Walhovd KB, Fjell AM, Reinvang I, Lundervold A, Dale AM, Eilertsen DE, et al. Effects of age on volumes of cortex, white matter and subcortical structures. Neurobiol. Aging. 2005;26:1261–1270
  83. Walterfang M, Wood SJ, Velakoulis D, Copolov D, Pantelis C. Diseases of white matter and schizophrenia-like psychosis. Aust. N. Z. J. Psychiatry. 2005;39:746–756
  84. Wang HD, Dunnavant FD, Jarman T, Deutch AY. Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat. Neuropsychopharmacology. 2004;29:1230–1238
  85. Wang Q, Wang Z, Zhu P, Jiang J. Alterations of myelin basic protein and ultrastructure in the limbic system at the early stage of trauma-related stress disorder in dogs. J. Trauma. 2004;56:604–610
  86. Woo TU, Crowell AL. Targeting synapses and myelin in the prevention of schizophrenia. Schizophr. Res. 2005;73:193–207
  87. Yakovlev PI, Lecours AR. Regional Development of the Brain in Early Life. Boston: Blackwell Scientific Publications; 1967;
  88. Zai G, Bezchlibnyk YB, Richter MA, Arnold P, Burroughs E, Barr CL, et al. Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive–compulsive disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2004;129:64–68

☆ Presented in part at the Society of Biological Psychiatry's 60th Annual Meeting, Atlanta, GA, May 2005.

PII: S0920-9964(07)00102-8

doi: 10.1016/j.schres.2007.02.011

Schizophrenia Research
Volume 93, Issue 1 , Pages 13-22 , July 2007

Article Tools

* Image Usage & Resolution