Brain Development on Adults with Schizophrenia

Summary

Principal Investigator: G Bartzokis
Abstract: [unreadable] DESCRIPTION (provided by applicant): Magnetic resonance imaging has shown that normal brain development continues into the mid-to-late 40's when maximal white matter volumes are reached in the frontal and temporal lobes. This confirms postmortem evidence suggesting that myelination of these brain areas continues into the 40's. Myelin is crucial for normal brain function because it increases the speed of axonal transmission. The increase in myelination is well regulated and occurs in concert with a decrease in gray matter volume resulting in a constant brain volume in adulthood. Schizophrenia is believed to be a disease caused in part by abnormal brain development. We observed that when examined crossectionally, brain development was dysregulated in adult schizophrenic subjects with an absence of normal myelination in adulthood. This project will examine gray and white matter volume changes in schizophrenia and normal adults prospectively by rescanning cohorts of subjects that were initially scanned 5 and 11 years ago. The project will more definitively test the theory that in schizophrenia, brain development is dysregulated in adulthood and will examine whether patients that have a poor outcome are particularly likely to suffer from this developmental problem in adulthood. If confirmed, the prevailing concept of a fixed and therefore unreparable brain developmental problem causing all schizophrenia will be surpassed. This will change our concept of how we could treat this illness, the feasibility of changing its lifelong course, and would encourage the development of novel pharmacologic interventions to improve myelination. [unreadable] [unreadable]
Funding Period: 2004-03-01 - 2010-02-28
more information: NIH RePORT

Top Publications

  1. ncbi Apolipoprotein E genotype and age-related myelin breakdown in healthy individuals: implications for cognitive decline and dementia
    George Bartzokis
    Department of Neurology, The David Geffen School of Medicine at UCLA, USA
    Arch Gen Psychiatry 63:63-72. 2006
  2. pmc Impact on intracortical myelination trajectory of long acting injection versus oral risperidone in first-episode schizophrenia
    George Bartzokis
    Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine at UCLA, Los Angeles, California, USA
    Schizophr Res 140:122-8. 2012
  3. pmc Neuroglialpharmacology: myelination as a shared mechanism of action of psychotropic treatments
    George Bartzokis
    Department of Psychiatry, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Neuropharmacology 62:2137-53. 2012
  4. pmc Premenopausal hysterectomy is associated with increased brain ferritin iron
    Todd A Tishler
    Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Neurobiol Aging 33:1950-8. 2012
  5. pmc Long acting injection versus oral risperidone in first-episode schizophrenia: differential impact on white matter myelination trajectory
    George Bartzokis
    Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine at UCLA, Los Angeles, California, United States
    Schizophr Res 132:35-41. 2011
  6. pmc Gender and iron genes may modify associations between brain iron and memory in healthy aging
    George Bartzokis
    Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 6968, USA
    Neuropsychopharmacology 36:1375-84. 2011
  7. pmc Apolipoprotein E genotype is associated with temporal and hippocampal atrophy rates in healthy elderly adults: a tensor-based morphometry study
    Po H Lu
    Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 7226, USA
    J Alzheimers Dis 23:433-42. 2011
  8. pmc Prevalent iron metabolism gene variants associated with increased brain ferritin iron in healthy older men
    George Bartzokis
    Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 6968, USA
    J Alzheimers Dis 20:333-41. 2010
  9. pmc Alzheimer's disease as homeostatic responses to age-related myelin breakdown
    George Bartzokis
    Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Neurobiol Aging 32:1341-71. 2011
  10. pmc In vivo evidence of differential impact of typical and atypical antipsychotics on intracortical myelin in adults with schizophrenia
    George Bartzokis
    Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 6968, USA
    Schizophr Res 113:322-31. 2009

Detail Information

Publications18

  1. ncbi Apolipoprotein E genotype and age-related myelin breakdown in healthy individuals: implications for cognitive decline and dementia
    George Bartzokis
    Department of Neurology, The David Geffen School of Medicine at UCLA, USA
    Arch Gen Psychiatry 63:63-72. 2006
    ..This may result in a progressive "disconnection" of widely distributed neural networks that may underlie the age risk factor for AD...
  2. pmc Impact on intracortical myelination trajectory of long acting injection versus oral risperidone in first-episode schizophrenia
    George Bartzokis
    Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine at UCLA, Los Angeles, California, USA
    Schizophr Res 140:122-8. 2012
    ..Insofar as the trajectory of ICM decline in chronic SZ is due to medication non-adherence or pharmacokinetics, it may be modifiable by long acting injection (LAI) formulations...
  3. pmc Neuroglialpharmacology: myelination as a shared mechanism of action of psychotropic treatments
    George Bartzokis
    Department of Psychiatry, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Neuropharmacology 62:2137-53. 2012
    ..Such efforts may provide insights into novel avenues for treatment and prevention of some of the most prevalent and devastating human diseases...
  4. pmc Premenopausal hysterectomy is associated with increased brain ferritin iron
    Todd A Tishler
    Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Neurobiol Aging 33:1950-8. 2012
    ..It is possible that brain iron can be influenced by peripheral iron levels and may thus be a modifiable risk factor for age-related degenerative diseases...
  5. pmc Long acting injection versus oral risperidone in first-episode schizophrenia: differential impact on white matter myelination trajectory
    George Bartzokis
    Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine at UCLA, Los Angeles, California, United States
    Schizophr Res 132:35-41. 2011
    ..Insofar as the trajectory of WM decline associated with chronic disease may be due to medication non-adherence, it may be modifiable by long acting injection (LAI) formulations...
  6. pmc Gender and iron genes may modify associations between brain iron and memory in healthy aging
    George Bartzokis
    Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 6968, USA
    Neuropsychopharmacology 36:1375-84. 2011
    ..Combining genetic and MRI biomarkers may provide opportunities to design primary prevention clinical trials that target high-risk groups...
  7. pmc Apolipoprotein E genotype is associated with temporal and hippocampal atrophy rates in healthy elderly adults: a tensor-based morphometry study
    Po H Lu
    Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 7226, USA
    J Alzheimers Dis 23:433-42. 2011
    ..Possession of the ε4 allele is associated with greater temporal and hippocampal volume reduction well before the onset of cognitive deficits...
  8. pmc Prevalent iron metabolism gene variants associated with increased brain ferritin iron in healthy older men
    George Bartzokis
    Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 6968, USA
    J Alzheimers Dis 20:333-41. 2010
    ..Clarifying mechanisms of brain iron accumulation may help identify novel interventions for age-related neurodegenerative diseases...
  9. pmc Alzheimer's disease as homeostatic responses to age-related myelin breakdown
    George Bartzokis
    Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Neurobiol Aging 32:1341-71. 2011
    ..Such interventions could potentially treat multiple degenerative brain disorders by mitigating the effects of aging and associated changes in iron, cholesterol, and free radicals on oligodendrocytes and their myelin...
  10. pmc In vivo evidence of differential impact of typical and atypical antipsychotics on intracortical myelin in adults with schizophrenia
    George Bartzokis
    Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 6968, USA
    Schizophr Res 113:322-31. 2009
    ..Increased white matter (WM) volume suggestive of increased myelination was detected in the patient group treated with an atypical antipsychotic compared to a typical one...
  11. pmc Lifespan trajectory of myelin integrity and maximum motor speed
    George Bartzokis
    Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA
    Neurobiol Aging 31:1554-62. 2010
    ..We tested the hypothesis that the age-related trajectory of FTS is related to brain myelin integrity...
  12. pmc Human brain myelination and amyloid beta deposition in Alzheimer's disease
    George Bartzokis
    Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
    Alzheimers Dement 3:122-5. 2007
    ....
  13. ncbi Apolipoprotein E affects both myelin breakdown and cognition: implications for age-related trajectories of decline into dementia
    George Bartzokis
    Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
    Biol Psychiatry 62:1380-7. 2007
    ..Apolipoprotein E (ApoE) 4 allele is the second most important AD risk factor. We tested the hypothesis that ApoE4 accelerates age-related slowing in CPS through the process of myelin breakdown...
  14. ncbi Myelin breakdown and iron changes in Huntington's disease: pathogenesis and treatment implications
    George Bartzokis
    Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Neurochem Res 32:1655-64. 2007
    ..A unique combination of in vivo tissue integrity and iron level assessments was used to examine the hypothesis...
  15. pmc Differential effects of typical and atypical antipsychotics on brain myelination in schizophrenia
    George Bartzokis
    Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1769, United States
    Schizophr Res 93:13-22. 2007
    ..Atypical antipsychotics have been shown to have a wide spectrum of efficacy across multiple psychiatric diseases and to be particularly efficacious in treatment resistant cases of disorders such as schizophrenia...
  16. ncbi Relationship between white matter fractional anisotropy and other indices of cerebral health in normal aging: tract-based spatial statistics study of aging
    P Kochunov
    Research Imaging Center, University of Texas Health Science Center at San Antonio, Research Imaging Center, 7703 Floyd Curl Drive, San Antonio, TX 78284, USA
    Neuroimage 35:478-87. 2007
    ..These data are consistent with the hypothesis that late-myelinating regions of the brain bear the brunt of age-related degenerative changes...
  17. ncbi Brain ferritin iron may influence age- and gender-related risks of neurodegeneration
    George Bartzokis
    Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Neurobiol Aging 28:414-23. 2007
    ..We hypothesized that brain iron may influence both the age- and gender-related risks of developing these diseases...
  18. pmc Methodological improvements in voxel-based analysis of diffusion tensor images: applications to study the impact of apolipoprotein E on white matter integrity
    Shawn M Newlander
    Department of Physics, San Diego State University, San Diego, California, USA
    J Magn Reson Imaging 39:387-97. 2014
    ....