Dysregulated brain development in adult men with schizophrenia: a magnetic resonance imaging study

  • George Bartzokis
    Address reprint requests to George Bartzokis, M.D., University of California, Los Angeles, Alzheimer’s Disease Center, 710 Westwood Plaza, RNRC, Room 2-238, Los Angeles CA 90095-1769, USA.
    Department of Neurology (GB), University of California School of Medicine, Los Angeles, California USA

    Laboratory of Neuroimaging, Department of Neurology, Division of Brain Mapping (GB), University of California School of Medicine, Los Angeles, California USA

    Greater Los Angeles VA Healthcare System (GB, PHL, SR, JM), West Los Angeles, California, USA
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  • Keith H Nuechterlein
    Department of Psychiatry (KHN, PHL, MG, JM), University of California School of Medicine, Los Angeles, California, USA
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  • P.o H Lu
    Department of Psychiatry (KHN, PHL, MG, JM), University of California School of Medicine, Los Angeles, California, USA

    Greater Los Angeles VA Healthcare System (GB, PHL, SR, JM), West Los Angeles, California, USA
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  • Michael Gitlin
    Department of Psychiatry (KHN, PHL, MG, JM), University of California School of Medicine, Los Angeles, California, USA
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  • Steven Rogers
    Greater Los Angeles VA Healthcare System (GB, PHL, SR, JM), West Los Angeles, California, USA
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  • Jim Mintz
    Department of Psychiatry (KHN, PHL, MG, JM), University of California School of Medicine, Los Angeles, California, USA

    Greater Los Angeles VA Healthcare System (GB, PHL, SR, JM), West Los Angeles, California, USA
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      Recent imaging evidence suggests that normal brain development/maturation of the frontal lobes and association areas is a well-regulated process consisting of continued myelination and expansion of white matter volumes into the late 40s accompanied by complementary reductions in gray matter volumes. The possibility that a dysregulation of this process may contribute to the syndrome of schizophrenia was investigated using magnetic resonance imaging.


      Fifty-two normal adult males and 35 males with schizophrenia underwent magnetic resonance imaging. Coronal images were acquired using pulse sequences that maximized myelin signal. The age-related change in the gray to white matter ratio was used as a measure of developmental dysregulation in the schizophrenic subjects and contrasted to the age-related changes of the normal control group.


      Regression analyses on frontal and temporal gray to white matter ratio yielded highly significant interactions of diagnosis and age for both regions (p = .0003 and p = .01, respectively). In the normal group, both frontal and temporal gray to white matter ratios decreased significantly and linearly across the age range. In contrast, neither ratio showed meaningful age-related change in the schizophrenia group. Thus, differences in gray to white matter ratio between the groups increased markedly with age, driven primarily by the absence of a white matter volume expansion in the patient group.


      The absence of the normal complementary volume changes in the gray and white matter with age in the schizophrenic sample suggests that this dynamic developmental process is dysregulated in adult schizophrenic subjects. The importance of myelination to the continued maturation and normal functioning of the brain has implications for the diagnosis, treatment, and prognosis of schizophrenia.


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