Decrease in Reelin and Glutamic Acid Decarboxylase 67 (GAD 67 ) Expression in Schizophrenia and Bipolar Disorder

Results: Prefrontal cortex and cerebellar expression of RELN mRNA, GAD67 protein and mRNA, and prefrontal cortex RELN-positive cells was significantly decreased by 30% to 50% in patients with schizophrenia or bipolar disorder with psychosis, but not in those with unipolar depression without psychosis when compared with nonpsychiatric subjects. Group differences were absent for DAB1,GAD65 and neuron-specific‐enolase expression implying that RELN and GAD67 down-regulations were unrelated to neuronal damage. Reelin and GAD67 were also unrelated to postmortem intervals, dose, duration, or presence of antipsychotic medication. Conclusions: The selective down-regulation of RELN and GAD67 in prefrontal cortex of patients with schizophrenia and bipolar disorder who have psychosis is consistent with the hypothesis that these parameters are vulnerability factors in psychosis; this plus the loss of the correlation between these 2 parameters that exists in nonpsychotic subjects support the hypothesis that these changes may be liability factors underlying psychosis. Arch Gen Psychiatry. 2000;57:1061-1069

[1]  C. Mao,et al.  The effects of antipsychotics on the turnover rate of GABA and acetylcholine in rat brain nuclei , 1976, Nature.

[2]  E. Torrey.  Surviving Schizophrenia: A Family Manual , 1983 .

[3]  R. Shelton,et al.  Cerebral structural pathology in schizophrenia: evidence for a selective prefrontal cortical defect. , 1988, The American journal of psychiatry.

[4]  M. Erlander,et al.  Two genes encode distinct glutamate decarboxylases , 1991, Neuron.

[5]  F. Benes,et al.  Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients. , 1991, Archives of general psychiatry.

[6]  A. MacDonald,et al.  Vulnerability to delusions over time in schizophrenia and affective disorders. , 1995, Schizophrenia bulletin.

[7]  T. Curran,et al.  A protein related to extracellular matrix proteins deleted in the mouse mutant reeler , 1995, Nature.

[8]  E. G. Jones,et al.  Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. , 1995, Archives of general psychiatry.

[9]  L. Tsai,et al.  Mice Lacking p35, a Neuronal Specific Activator of Cdk5, Display Cortical Lamination Defects, Seizures, and Adult Lethality , 1997, Neuron.

[10]  Jonathan A. Cooper,et al.  Neuronal position in the developing brain is regulated by mouse disabled-1 , 1997, Nature.

[11]  D. Lewis,et al.  Development of the Prefrontal Cortex during Adolescence: Insights into Vulnerable Neural Circuits in Schizophrenia , 1997, Neuropsychopharmacology.

[12]  Yogesh K. Dwivedi,et al.  A decrease of reelin expression as a putative vulnerability factor in schizophrenia. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[13]  D. L. Martin,et al.  Two isoforms of glutamate decarboxylase: why? , 1998, Trends in pharmacological sciences.

[14]  S. Hirsch,et al.  Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia , 1998, Journal of neurology, neurosurgery, and psychiatry.

[15]  K. Herrup,et al.  Cyclin-Dependent Kinase 5-Deficient Mice Demonstrate Novel Developmental Arrest in Cerebral Cortex , 1998, The Journal of Neuroscience.

[16]  T. Woo,et al.  A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[17]  A. Guidotti,et al.  Reelin is preferentially expressed in neurons synthesizing gamma-aminobutyric acid in cortex and hippocampus of adult rats. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[18]  C. Sotelo,et al.  Regional and Cellular Patterns of reelin mRNA Expression in the Forebrain of the Developing and Adult Mouse , 1998, The Journal of Neuroscience.

[19]  G. Meyer,et al.  Prenatal development of reelin‐immunoreactive neurons in the human neocortex , 1998, The Journal of comparative neurology.

[20]  Joachim Herz,et al.  Direct Binding of Reelin to VLDL Receptor and ApoE Receptor 2 Induces Tyrosine Phosphorylation of Disabled-1 and Modulates Tau Phosphorylation , 1999, Neuron.

[21]  Ramin Homayouni,et al.  Reelin Is a Ligand for Lipoprotein Receptors , 1999, Neuron.

[22]  Yogesh K. Dwivedi,et al.  The phenotypic characteristics of heterozygous reeler mouse. , 1999, Neuroreport.

[23]  A. Guidotti,et al.  Cortical bitufted, horizontal, and Martinotti cells preferentially express and secrete reelin into perineuronal nets, nonsynaptically modulating gene expression. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[24]  T. Curran,et al.  Mutant mice with scrambled brains: understanding the signaling pathways that control cell positioning in the CNS. , 1999, Genes & development.

[25]  Martha E Shenton,et al.  P300 topography differs in schizophrenia and manic psychosis , 1999, Biological Psychiatry.

[26]  N. Toni,et al.  LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite , 1999, Nature.

[27]  A. Sampson,et al.  Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia. , 2000, Archives of general psychiatry.

[28]  D. Lewis,et al.  Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. , 2000, Archives of general psychiatry.

[29]  Erminio Costa,et al.  Colocalization of integrin receptors and reelin in dendritic spine postsynaptic densities of adult nonhuman primate cortex , 2000 .

[30]  C. Walsh,et al.  Reelin Binds α3β1 Integrin and Inhibits Neuronal Migration , 2000, Neuron.

[31]  R. Yolken,et al.  The Stanley Foundation brain collection and Neuropathology Consortium , 2000, Schizophrenia Research.