DEVELOPMENTAL INSULT AND BRAIN ANOMALY IN SCHIZOPHRENIA

Summary

Principal Investigator: ALAN STEWART BROWN
Abstract: DESCRIPTION: (Adapted from applicant's abstract) This study will investigate the relation of early developmental insult (EDI) to adult brain disturbance among cases of schizophrenia and schizophrenia spectrum disorder (SSD). The study represents a collaborative effort between epidemiologists and clinical neuroscientists, in which advanced neuroimaging and neuropsychological approaches are brought to bear on a large birth cohort with extensive early developmental exposure data. The proposal study builds upon two unique investigations, the Child Health and Development Study (CHDS) and one of its extensions, the Prenatal Determinants of Schizophrenia (PDS) Study. The CHDS was based on a cohort of 19,044 live births during 1959-1966 in the Oakland Hospital of the Kaiser Foundation Health Plan (KFHP). Using cases already diagnosed in the PDS study, and cases to be diagnosed in the present study, we expect that 100-11O cases and 100-110 matched controls will be assessed for all the proposed adult brain disturbances. Specifically, the applicants aim to: 1) Compare case of SSD with matched controls from the PDS study with respect to adult brain disturbances indicative of early development insult. The applicants hypothesize that associations will be demonstrated between SSD and adult brain disturbances in the following dimensions: neuroanatomical, neurochemical, and neuropsychological; 2) Examine, among cases of SSD, associations between EDI and adult brain disturbances; and 3) For those adult brain disturbances that show a relation to ED! in Aim 2, the applicants will then examine evidence for whether familial liability to SSD contributes to EDI, leading to the above adult brain abnormalities in SSD cases. This study has several notable strengths, which include: extensive prospectively collected data on EDT and prenatal sera for analysis of additional early developmental exposures; research-based diagnoses; good control of bias; a representative sample of control subjects; more refined and extensive brain measures; good statistical power; and the ability to analyze causal pathways. Important implications of this study are to provide evidence of pathogenic mechanisms by which ED! might lead to SSD, lend validation for the neurodevelopment hypothesis of schizophrenia, and elucidate underpinnings of the diverse brain disturbances found in patients with SSD.
Funding Period: 2001-03-15 - 2006-02-28
more information: NIH RePORT

Top Publications

  1. pmc Low maternal hemoglobin during pregnancy and diminished neuromotor and neurocognitive performance in offspring with schizophrenia
    Lauren M Ellman
    Department of Psychology, Temple University, Philadelphia, PA, USA
    Schizophr Res 138:81-7. 2012
  2. pmc Birth weight and neurocognition in schizophrenia spectrum disorders
    David Freedman
    Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 West 168th Street, 7th Floor, New York, NY 10032, USA
    Schizophr Bull 39:592-600. 2013
  3. pmc Maternal iron deficiency and the risk of schizophrenia in offspring
    Beverly J Insel
    New York State Psychiatric Institute, 1051 Riverside Dr, Unit 23, New York, NY 10032, USA
    Arch Gen Psychiatry 65:1136-44. 2008
  4. pmc Association of maternal genital and reproductive infections with verbal memory and motor deficits in adult schizophrenia
    Alan S Brown
    Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York, NY, USA
    Psychiatry Res 188:179-86. 2011
  5. pmc Maternal-fetal blood incompatibility and neuromorphologic anomalies in schizophrenia: Preliminary findings
    David Freedman
    Department of Epidemiology, Mailman School of Public Health of Columbia University, New York, NY, USA
    Prog Neuropsychopharmacol Biol Psychiatry 35:1525-9. 2011
  6. pmc The developmental course of executive functioning in schizophrenia
    David Freedman
    Department of Epidemiology, Mailman School of Public Health of Columbia University, New York, NY 10032, USA
    Int J Dev Neurosci 29:237-43. 2011
  7. pmc Structural brain alterations in schizophrenia following fetal exposure to the inflammatory cytokine interleukin-8
    Lauren M Ellman
    Department of Psychology, Temple University, Philadelphia, PA 19122 6085, United States
    Schizophr Res 121:46-54. 2010
  8. pmc Cognitive decline in schizophrenia from childhood to midlife: a 33-year longitudinal birth cohort study
    William S Kremen
    Department of Psychiatry, Center for Behavioral Genomics, University of California, San Diego, CA, United States
    Schizophr Res 118:1-5. 2010
  9. pmc Prenatal infection and schizophrenia: a review of epidemiologic and translational studies
    Alan S Brown
    New York State Psychiatric Institute, New York, NY 10032, USA
    Am J Psychiatry 167:261-80. 2010
  10. pmc Prenatal exposure to maternal infection and executive dysfunction in adult schizophrenia
    Alan S Brown
    New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, 1051 Riverside Dr, Unit 23, New York, NY 10032, USA
    Am J Psychiatry 166:683-90. 2009

Scientific Experts

Detail Information

Publications14

  1. pmc Low maternal hemoglobin during pregnancy and diminished neuromotor and neurocognitive performance in offspring with schizophrenia
    Lauren M Ellman
    Department of Psychology, Temple University, Philadelphia, PA, USA
    Schizophr Res 138:81-7. 2012
    ..However, no study has sought to determine whether this early insult leads to a more severe form of the disorder, characterized by worsened motor and neurocognitive functioning...
  2. pmc Birth weight and neurocognition in schizophrenia spectrum disorders
    David Freedman
    Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 West 168th Street, 7th Floor, New York, NY 10032, USA
    Schizophr Bull 39:592-600. 2013
    ..The sample consisted of all subjects in the Developmental Insult and Brain Anomaly in Schizophrenia study, a nested case-control investigation developed from a large birth cohort, which ..
  3. pmc Maternal iron deficiency and the risk of schizophrenia in offspring
    Beverly J Insel
    New York State Psychiatric Institute, 1051 Riverside Dr, Unit 23, New York, NY 10032, USA
    Arch Gen Psychiatry 65:1136-44. 2008
    ..Adopting a life course perspective, we examined the effects of early iron deficiency on the risk of schizophrenia in adulthood...
  4. pmc Association of maternal genital and reproductive infections with verbal memory and motor deficits in adult schizophrenia
    Alan S Brown
    Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York, NY, USA
    Psychiatry Res 188:179-86. 2011
    ..Although independent replications are warranted, maternal G/R infections were associated with verbal memory and motor function deficits in African-American patients with schizophrenia...
  5. pmc Maternal-fetal blood incompatibility and neuromorphologic anomalies in schizophrenia: Preliminary findings
    David Freedman
    Department of Epidemiology, Mailman School of Public Health of Columbia University, New York, NY, USA
    Prog Neuropsychopharmacol Biol Psychiatry 35:1525-9. 2011
    ..The findings also suggest that the larger hippocampal volume in exposed controls may indicate a mechanism of adaptive resilience which diminishes the risk that controls will develop schizophrenia...
  6. pmc The developmental course of executive functioning in schizophrenia
    David Freedman
    Department of Epidemiology, Mailman School of Public Health of Columbia University, New York, NY 10032, USA
    Int J Dev Neurosci 29:237-43. 2011
    ....
  7. pmc Structural brain alterations in schizophrenia following fetal exposure to the inflammatory cytokine interleukin-8
    Lauren M Ellman
    Department of Psychology, Temple University, Philadelphia, PA 19122 6085, United States
    Schizophr Res 121:46-54. 2010
    ..This study sought to determine the association between fetal exposure to IL-8 and structural brain changes among schizophrenia cases and controls...
  8. pmc Cognitive decline in schizophrenia from childhood to midlife: a 33-year longitudinal birth cohort study
    William S Kremen
    Department of Psychiatry, Center for Behavioral Genomics, University of California, San Diego, CA, United States
    Schizophr Res 118:1-5. 2010
    ....
  9. pmc Prenatal infection and schizophrenia: a review of epidemiologic and translational studies
    Alan S Brown
    New York State Psychiatric Institute, New York, NY 10032, USA
    Am J Psychiatry 167:261-80. 2010
    ..Finally, they discuss new approaches aimed at addressing current challenges in this area of research...
  10. pmc Prenatal exposure to maternal infection and executive dysfunction in adult schizophrenia
    Alan S Brown
    New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, 1051 Riverside Dr, Unit 23, New York, NY 10032, USA
    Am J Psychiatry 166:683-90. 2009
    ..The authors examined whether prenatal infection is associated with executive dysfunction in patients with schizophrenia...
  11. pmc Prenatal infection and cavum septum pellucidum in adult schizophrenia
    Alan S Brown
    Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, Mailman School of Public Health, 1051 Riverside Drive, Unit 23, New York, NY 10032, USA
    Schizophr Res 108:285-7. 2009
    ....
  12. ncbi Congenital anomalies and early functional impairments in a prospective birth cohort: risk of schizophrenia-spectrum disorder in adulthood
    John L Waddington
    Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, St Stephen s Green, Dublin 2, Ireland
    Br J Psychiatry 192:264-7. 2008
    ..Adversities operating over intrauterine life have been associated with risk of schizophrenia, but the biology of resultant developmental perturbation is poorly understood...
  13. pmc Aberrant epigenetic regulation could explain the relationship of paternal age to schizophrenia
    Mary C Perrin
    Department of Psychiatry, School of Medicine, New York University, New York, NY, USA
    Schizophr Bull 33:1270-3. 2007
    ..This article will discuss parental imprinting on the autosomal and X chromosomes and the alterations in epigenetic regulation that may lead to such errors...
  14. ncbi Does unwantedness of pregnancy predict schizophrenia in the offspring? Findings from a prospective birth cohort study
    Daniel B Herman
    New York State Psychiatric Institute, New York, NY, USA
    Soc Psychiatry Psychiatr Epidemiol 41:605-10. 2006
    ..We sought to replicate (or refute) a previous report of an association between unwantedness of a pregnancy and the risk of schizophrenia in the offspring...