title: Conserved regional patterns of GABA-related transcript expression in the neocortex of subjects with schizophrenia.
abstract: OBJECTIVE
  Individuals with schizophrenia exhibit disturbances in a number of cognitive, affective, sensory, and motor functions that depend on the circuitry of different cortical areas. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex result, at least in part, from abnormalities in GABA neurotransmission, as reflected in a specific pattern of altered expression of GABA-related genes. Consequently, the authors sought to determine whether this pattern of altered gene expression is restricted to the dorsolateral prefrontal cortex or could also contribute to the dysfunction of other cortical areas in subjects with schizophrenia.
  
  
  METHODS
  Real-time quantitative polymerase chain reaction was used to assess the levels of eight GABA-related transcripts in four cortical areas (dorsolateral prefrontal cortex, anterior cingulate cortex, and primary motor and primary visual cortices) of subjects (N=12) with schizophrenia and matched normal comparison subjects.
  
  
  RESULTS
  Expression levels of seven transcripts were lower in subjects with schizophrenia, with the magnitude of reduction for each transcript comparable across the four areas. The largest reductions were detected for mRNA encoding somatostatin and parvalbumin, followed by moderate decreases in mRNA expression for the 67-kilodalton isoform of glutamic acid decarboxylase, the GABA membrane transporter GAT-1, and the alpha 1 and delta subunits of GABA(A) receptors. In contrast, the expression of calretinin mRNA did not differ between the subject groups in any of the four areas.
  
  
  CONCLUSIONS
  Because the areas examined represent the major functional domains (e.g., association, limbic, motor, and sensory) of the cerebral cortex, our findings suggest that a conserved set of molecular alterations affecting GABA neurotransmission contribute to the pathophysiology of different clinical features of schizophrenia.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Takanori
authors.initials: T
authors.lastname: Hashimoto
authors.forename: H Holly
authors.initials: HH
authors.lastname: Bazmi
authors.forename: Karoly
authors.initials: K
authors.lastname: Mirnics
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Allan R
authors.initials: AR
authors.lastname: Sampson
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
mesh_terms: D000328:Adult; D000368:Aged; D002423:Cause of Death; D005260:Female; D020869:Gene Expression Profiling; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000378:metabolism; D019579:Neocortex / Q000737:chemistry / Q000378:metabolism*; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017397:Prefrontal Cortex / Q000737:chemistry / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D014018:Tissue Distribution / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000235:genetics* / Q000378:metabolism
chemical_list: D010320:Parvalbumins; D011963:Receptors, GABA-A; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase