Variations in differential gene expression patterns across multiple brain regions in schizophrenia.
Large-scale gene expression studies in schizophrenia (SZ) have generally focused on the dorsolateral prefrontal cortex. Despite a wealth of evidence implicating multiple other brain regions in the disease, studies of other brain regions have been less frequent and have rarely been performed in the same subjects. We analyzed postmortem gene expression in the frontal, cingulate, temporal, parietal and occipital cortices (Brodmann areas 8, 10, 44, 46, 23/31, 24/32, 20, 21, 22, 36/28, 7 and 17, respectively) as well as in the hippocampus, caudate nucleus and putamen of persons with schizophrenia and control subjects (N's = 13) using Affymetrix GeneChip microarrays. Under identical data filtering conditions, the superior temporal cortex (BA22) of schizophrenia subjects showed the maximal number of altered transcripts (approximately 1200) compared to controls. Anterior and posterior cingulate cortices (BA23/31, 24/32) and the hippocampus followed the superior temporal cortex with two-times lower numbers of altered transcripts. The dorsolateral prefrontal cortex (BA46), a frequent target of SZ-associated studies, showed substantially fewer altered transcripts (approximately 33). These regional differences in differentially expressed genes could not be accounted for by factors such as total numbers of genes expressed or the filtering conditions and criteria used for identification of differentially expressed genes. These findings suggest that the temporal and cingulate cortices and the hippocampal formation represent brain regions of particular abnormality in SZ and may be more susceptible to the disease process(es) than other regions thus far studied.
Katsel
P
P
Department of Psychiatry, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6575, USA.
Davis
K L
KL
Gorman
J M
JM
Haroutunian
V
V
D000368:Aged; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006179:Gyrus Cinguli / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018709:Statistics, Nonparametric; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution