title: Altered cortical expression of GABA-related genes in schizophrenia: illness progression vs developmental disturbance.
abstract: BACKGROUND
  Schizophrenia is a neurodevelopmental disorder with altered expression of GABA-related genes in the prefrontal cortex (PFC). However, whether these gene expression abnormalities reflect disturbances in postnatal developmental processes before clinical onset or arise as a consequence of clinical illness remains unclear.
  
  
  METHODS
  Expression levels for 7 GABA-related transcripts (vesicular GABA transporter [vGAT], GABA membrane transporter [GAT1], GABAA receptor subunit α1 [GABRA1] [novel in human and monkey cohorts], glutamic acid decarboxylase 67 [GAD67], parvalbumin, calretinin, and somatostatin [previously reported in human cohort, but not in monkey cohort]) were quantified in the PFC from 42 matched pairs of schizophrenia and comparison subjects and from 49 rhesus monkeys ranging in age from 1 week postnatal to adulthood.
  
  
  RESULTS
  Levels of vGAT and GABRA1, but not of GAT1, messenger RNAs (mRNAs) were lower in the PFC of the schizophrenia subjects. As previously reported, levels of GAD67, parvalbumin, and somatostatin, but not of calretinin, mRNAs were also lower in these subjects. Neither illness duration nor age accounted for the levels of the transcripts with altered expression in schizophrenia. In monkey PFC, developmental changes in expression levels of many of these transcripts were in the opposite direction of the changes observed in schizophrenia. For example, mRNA levels for vGAT, GABRA1, GAD67, and parvalbumin all increased with age.
  
  
  CONCLUSIONS
  Together with published reports, these findings support the interpretation that the altered expression of GABA-related transcripts in schizophrenia reflects a blunting of normal postnatal development changes, but they cannot exclude a decline during the early stages of clinical illness.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA; Department of Neuroscience, Medical Scientist Training Program, University of Pittsburgh, Pittsburgh, PA;
authors.forename: Gil D
authors.initials: GD
authors.lastname: Hoftman
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA;
authors.forename: David W
authors.initials: DW
authors.lastname: Volk
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA;
authors.forename: H Holly
authors.initials: HH
authors.lastname: Bazmi
authors.affiliation: Department of Statistics, University of Pittsburgh, Pittsburgh, PA;
authors.forename: Siyu
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Statistics, University of Pittsburgh, Pittsburgh, PA;
authors.forename: Allan R
authors.initials: AR
authors.lastname: Sampson
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA; Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA lewisda@upmc.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
mesh_terms: D000328:Adult; D000818:Animals; D064032:Calbindin 2 / Q000235:genetics; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005968:Glutamate Decarboxylase / Q000235:genetics; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D010320:Parvalbumins / Q000235:genetics; D017397:Prefrontal Cortex / Q000254:growth & development / Q000378:metabolism*; D011618:Psychotic Disorders / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D013004:Somatostatin / Q000235:genetics; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C576764:CALB2 protein, human; D064032:Calbindin 2; D050485:GABA Plasma Membrane Transport Proteins; C546240:GABRA1 protein, human; D010320:Parvalbumins; D012333:RNA, Messenger; D011963:Receptors, GABA-A; C492245:SLC32A1 protein, human; C493413:SLC6A1 protein, human; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: GABA; neurodevelopment; parvalbumin; prefrontal cortex; schizophrenia