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Molecular abnormalities in the major psychiatric illnesses: Classification and Regression Tree (CRT) analysis of post-mortem prefrontal markers

Abstract

Post-mortem specimens from the Stanley Foundation Neuropathology Consortium, which contains matched samples from patients with schizophrenia, bipolar disorder, non-psychotic depression and normal controls (n = 15 per group), have been distributed to many research groups around the world. This paper provides a summary of abnormal markers found in prefrontal cortical areas from this collection between 1997 and 2001. With parametric analyses of variance of 102 separate data sets, 14 markers were abnormal in at least one disease. The markers pertained to a variety of neural systems and processes including neuronal plasticity, neurotransmission, signal transduction, inhibitory interneuron function and glial cells. The data sets were also examined using the non-parametric Classification and Regression Tree (CRT) technique for the four diagnostic groups and in pair-wise combinations. In contrast to the results obtained with analyses of variance, the CRT method identified a smaller set of nine markers that contributed maximally to the diagnostic classifications. Three of the nine markers observed with CRT overlapped with the ANOVA results. Six of the nine markers observed with the CRT technique pertained to aspects of glutamatergic, GABA-ergic, and dopaminergic neurotransmission.

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References

  1. Torrey EF Webster M Knable M Johnston N Yolken RH The Stanley Foundation Brain Collection and Neuropathology Consortium Schizophr Res 2000 44 151 155

    Article  CAS  PubMed  Google Scholar 

  2. Knable MB Torrey EF Webster MJ Bartko JJ Multivariate analysis of prefrontal cortical data from the Stanley Foundation Neuropathology Consortium Brain Res Bull 2001 55 651 659

    Article  CAS  PubMed  Google Scholar 

  3. Knable MB Barci BM Webster MJ Torrey EF Summary of prefrontal molecular abnormalities in the Stanley Foundation Neuropathology Consortium. In: Agam G, Belmaker RH, Everall I (eds) The Post-Mortem Brain in Psychiatric Research Kluwer Academic Publishers: Boston 2002 105 137

    Chapter  Google Scholar 

  4. Broderik JP Lu M Kothari R Levine SR Lyden PD et alFinding the most powerful measures of the effectiveness of tissue plasminogen activator in the NINDS tPA stroke trial Stroke 2000 31 2335 2341

    Article  Google Scholar 

  5. Harbeck N Alt U Berger U Kates R Kruger A Thomssen C et alLong-term follow-up confirms prognostic impact of PAI-1 and cathepsin D and L in primary breast cancer Int J Biol Markers 2000 15 79 83

    Article  CAS  PubMed  Google Scholar 

  6. Breiman L Friedman JH Olshen R Classification and Regression Trees CRC Press: Boca Raton, FL 1993

    Google Scholar 

  7. Cohen J Statistical Power Analysis for the Behavioral Sciences. 2nd edn Lawrence Erlbaum: Hillsdale, NJ 1998p42

    Google Scholar 

  8. Akbarian S Kim JJ Potkin SG Hagman JO Tafazzoli A Bunney WE et alGene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenia Arch Gen Psychiatry 1995 52 258 266

    Article  CAS  PubMed  Google Scholar 

  9. Volk DW Austin MC Pierri JN Sampson AR Lewis DA Decreased glutamic acid decarboxylase 67 messenger RNA expression in a subset of prefrontal cortical gamma-amino butyric acid neurons in subjects with schizophrenia Arch Gen Psychiatry 2000 57 237 245

    Article  CAS  PubMed  Google Scholar 

  10. Guidotti A Auta J Davis JM Gervini VD Dwivedi Y Grayson DR et alDecrease in reelin and glutamic acid decarboxylase 67 (GAD67) expression in schizophrenia and bipolar disorder Arch Gen Psychiatry 2000 57 1061 1069

    Article  CAS  PubMed  Google Scholar 

  11. Sakai K Gao XM Hashimoto T Tamminga CA Traditional and new antipsychotic drugs differentially alter neurotransmission markers in basal ganglia-thalamocortical neural pathways Synapse 2001 39 152 160

    Article  CAS  PubMed  Google Scholar 

  12. Webster MJ Knable MB O'Grady JO Orthmann J Shannon-Weickert C Regional specificity of brain glucocorticoid receptor mRNA alterations in subjects with schizophrenia and mood disorders Mol Psychiatry(in press)

  13. Dingledine R Borges K Bowie D Traynelis SF Glutamate receptor ion channels Pharmacol Rev 1999 51 7 62

    CAS  PubMed  Google Scholar 

  14. Myers SJ Dingledine R Borges K Genetic regulation of glutamate receptor ion channels Annu Rev Pharmacol Toxicol 1999 39 221 241

    Article  CAS  PubMed  Google Scholar 

  15. Conti F Weinberg RJ Shaping excitation at glutamatergic synapses TINS 1999 22 451 458

    CAS  PubMed  Google Scholar 

  16. Akbarian S Sucher NJ Bradley D Tafazzoli A Trinh D Hetrick WP et alSelective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics J Neurosci 1996 16 19 30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Riva MA Tascedda F Lovati E Racagni G Regulation of NMDA receptor subunit messenger RNA levels in the rat brain following acute and chronic exposure to antipsychotic drugs Mol Brain Res 1997 50 136 142

    Article  CAS  PubMed  Google Scholar 

  18. Tascedda F Lovati E Blom JMC Muzzioli P Brunello N Racagni G et alRegulation of ionotropic glutamate receptors in the rat brain in response to the atypical antipsychotic Seroquel Neuropsychopharmacology 1999 21 211 217

    Article  CAS  PubMed  Google Scholar 

  19. Boyer PA Skonick P Fossom LH Chronic administration of imipramine and citalopram alters the expression of NMDA receptor subunit mRNAs in mouse brain. A quantitative in situ hybridization study J Mol Neurosci 1998 10 219 233

    Article  CAS  PubMed  Google Scholar 

  20. Petrie RX Reid IC Stewart CA The N-methyl-D-aspartate receptor, synaptic plasticity, and depressive disorder. A critical review Pharmacol Ther 2000 87 11 25

    Article  CAS  PubMed  Google Scholar 

  21. Healy DJ Meador-Woodruff JH Clozapine and haloperidol differentially affect AMPA and kainate receptor subunit mRNA levels in rat cortex and striatum Mol Brain Res 1997 47 331 338

    Article  CAS  PubMed  Google Scholar 

  22. Snyder SH Ferris CD Novel neurotransmitters and the neuropsychiatric relevance Am J Psychiatry 2000 157 1738 1751

    Article  CAS  PubMed  Google Scholar 

  23. Ferrer I Alpha-synucleinopathies Neurologia 2001 16 163 170

    CAS  PubMed  Google Scholar 

  24. Rosengren E Linder-Eliasson E Carlsson A Detection of 5-S-cysteinyldopamine in human brain J Neural Transm 1985 63 247 253

    Article  CAS  PubMed  Google Scholar 

  25. Carlsson A Waters N Hansson LO Neurotransmitter aberrations in schizophrenia: new findingsIn: Fog R, Gerlach J, Hemmingsen R (eds)SchizophreniaAlfred Benzon Symposium: Copenhagen1995pp332 340

  26. Hansson LO Waters N Winblad B Gottfries C-G Carlsson A Evidence for biochemical heterogeneity in schizophrenia: a multi-variate study of monoaminergic indices in human post-mortem brain tissue J Neural Transm [Gen Sect] 1998 98 217 235

    Article  Google Scholar 

  27. Kozlovsky N Belmaker RH Agam G Low GSK-3β immunoreactivity in postmortem frontal cortex of schizophrenic patients Am J Psychiatry 2000 157 831 833

    Article  CAS  PubMed  Google Scholar 

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Knable, M., Barci, B., Bartko, J. et al. Molecular abnormalities in the major psychiatric illnesses: Classification and Regression Tree (CRT) analysis of post-mortem prefrontal markers. Mol Psychiatry 7, 392–404 (2002). https://doi.org/10.1038/sj.mp.4001034

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