Age-related changes in the expression of schizophrenia susceptibility genes in the human prefrontal cortex.
The molecular basis of complex neuropsychiatric disorders most likely involves many genes. In recent years, specific genetic variations influencing risk for schizophrenia and other neuropsychiatric disorders have been reported. We have used custom DNA microarrays and qPCR to investigate the expression of putative schizophrenia susceptibility genes and related genes of interest in the normal human brain. Expression of 31 genes was measured in Brodmann's area 10 (BA10) in the prefrontal cortex of 72 postmortem brain samples spanning half a century of human aging (18-67 years), each without history of neuropsychiatric illness, neurological disease, or drug abuse. Examination of expression across age allowed the identification of genes whose expression patterns correlate with age, as well as genes that share common expression patterns and that possibly participate in common cellular mechanisms related to the emergence of schizophrenia in early adult life. The expression of GRM3 and RGS4 decreased across the entire age range surveyed, while that of PRODH and DARPP-32 was shown to increase with age. NRG1, ERBB3, and NGFR show expression changes during the years of greatest risk for the development of schizophrenia. Expression of FEZ1, GAD1, and RGS4 showed especially high correlation with one another, in addition to the strongest mean levels of absolute correlation with all other genes studied here. All microarray data are available at NCBI's Gene Expression Omnibus: GEO Series accession number GSE11546 (http://www.ncbi.nlm.nih.gov/geo) [corrected]
Colantuoni
Carlo
C
Clinical Brain Disorders Branch, Genes Cognition and Psychosis Program, IRP, NIMH, NIH, Bethesda, MD 20892, USA. carlo@illuminatoart.com
Hyde
Thomas M
TM
Mitkus
Shruti
S
Joseph
Andrew
A
Sartorius
Leah
L
Aguirre
Claudia
C
Creswell
Johanna
J
Johnson
Elizabeth
E
Deep-Soboslay
Amy
A
Herman
Mary M
MM
Lipska
Barbara K
BK
Weinberger
Daniel R
DR
Kleinman
Joel E
JE
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005968:Glutamate Decarboxylase / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D020890:Neuregulin-1 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011180:Postmortem Changes; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D020710:RGS Proteins / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics*; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C528597:FEZ1 protein, human; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D020710:RGS Proteins; D017475:Receptors, Nerve Growth Factor; C098799:RGS4 protein; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1