Summary of Prefrontal Molecular Abnormalities in the Stanley Foundation Neuropathology Consortium
Postmortem 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 chapter provides a summary of abnormal markers found in prefrontal cortical areas from this collection between 1997 and 2000. From 69 separate data sets, a total of 17 abnormal markers were identified that pertained to a variety of neural systems and processes including neuronal plasticity, neurotransmission, signal transduction, inhibitory interneuron function, and glial cells. Schizophrenia was associated with the largest number of abnormalities, many of which were also present in bipolar disorder. Major depression was associated with relatively few abnormalities. Most abnormal findings represented a decrease in protein or mRNA levels that could not be fully explained by exposure to psychotropic or illicit drugs or by other confounding variables. It is argued that the abnormal findings are not due to stochastic processes but represent viable markers for independent replication and further study as candidate genes or targets for new treatments.
KeywordsBipolar Disorder Prefrontal Cortex Glial Fibrillary Acidic Protein Diagnostic Group Linear Discriminant Function
Unable to display preview. Download preview PDF.
- Cohen, J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed., Lawrence Erlbaum, Hillsdale, NJ, 1998; p 42.Google Scholar
- Fatemi SH. Reelin mutations in mouse and man: from reeler mouse to schizophrenia, mood disorders, autism and lissencephaly. Mol Psychiatry, in press.Google Scholar
- Guidotti A, Auta J, Davis JM, Gerevini VD, Dwivedi Y, Grayson DR, Impagnatiello F, Pandey G, Pesold C, Sharma R, Vzonov D, Costa E. Decrease in reelin and glutamic acid decarboxylase 67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study. Arch Gen Psychiatry 2000; 57: 1061–1069.PubMedCrossRefGoogle Scholar
- Impagnatiello F, Guidotti A, Pesold C, Dwivedi Y, Caruncho H, Pisu MG, Uzunov DP, Smalheiser NR, Davis JM, Pandey GN, Pappas GD, Tueting P, Sharma RP, Costa E. A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Proc Natl Acad Sci USA 1998; 95: 15718–15723.PubMedCrossRefGoogle Scholar
- Ohnuma T, Augood SJ, Arai H, McKenna Pi, Emson PC. Measurement of GABAergic parameters in the prefrontal cortex in schizophrenia: focus on GABA content, GABA(A) receptor alpha-1 subunit messenger RNA and human GABA transporter-1 (HGAT-1) messenger RNA expression. Neuroscience 1999; 93: 441–448.PubMedCrossRefGoogle Scholar
- Shapiro J, Belmaker RH, Bigeon A, Seher A, Agam A. Scyllo-inositol in postmortem brain of suicide victims, bipolar, unipolar and schizophrenic patients. J Neural Transm, in press.Google Scholar
- Song L, Greendorfer AJ, Bartolucci AA, Jope RS. Phosphoinositide signal transduction system and G-protein levels in postmortem brain from subjects with bipolar disorder, major depression, and schizophrenia. J Psychiatr Res, in press.Google Scholar
- Tom M, Watanabe S, Shibuya H, Nishikawa T, Noda K, Mitsushio H, Ichikawa H, Kurumaji A, Takashima M, Mataga N, Ogawa A. Neurotransmitters, receptors and neuropeptides in postmortem brains of chronic schizophrenic patients. Acta Psychiatr Scand 1988; 78: 121–137.Google Scholar
- Uranova NA, Vostrikov VM, Olovskaya DD, Rachmanova VI. Oligodendroglial density in the prefrontal cortex area 9 in schizophrenia and mood disorders: A study of the Stanley Foundation Neuropathology Consortium. Submitted manuscript.Google Scholar
- Xing G, Post R. Reduced Nurrl (NOTI) and NGFI-B (TR3) expression in the prefrontal cortex of schizophrenic and unipolar patients. Submitted manuscript.Google Scholar