Putative psychosis genes in the prefrontal cortex: combined analysis of gene expression microarrays.
BACKGROUND
Recent studies have shown similarities between schizophrenia and bipolar disorder in phenotypes and in genotypes, and those studies have contributed to an ongoing re-evaluation of the traditional dichotomy between schizophrenia and bipolar disorder. Bipolar disorder with psychotic features may be closely related to schizophrenia and therefore, psychosis may be an alternative phenotype compared to the traditional diagnosis categories.


METHODS
We performed a cross-study analysis of 7 gene expression microarrays that include both psychosis and non-psychosis subjects. These studies include over 400 microarray samples (163 individual subjects) on 3 different Affymetrix microarray platforms.


RESULTS
We found that 110 transcripts are differentially regulated (p < 0.001) in psychosis after adjusting for confounding variables with a multiple regression model. Using a quantitative PCR, we validated a set of genes such as up-regulated metallothioneins (MT1E, MT1F, MT1H, MT1K, MT1X, MT2A and MT3) and down-regulated neuropeptides (SST, TAC1 and NPY) in the dorsolateral prefrontal cortex of psychosis patients.


CONCLUSIONS
This study demonstrates the advantages of cross-study analysis in detecting consensus changes in gene expression across multiple microarray studies. Differential gene expression between individuals with and without psychosis suggests that psychosis may be a useful phenotypic variable to complement the traditional diagnosis categories.
Choi
Kwang Ho
KH
Stanley Laboratory of Brain Research, 9800 Medical Center Dr. Bldg 2C, Rockville, MD 20850, USA. choik@stanleyresearch.org
Elashoff
Michael
M
Higgs
Brandon W
BW
Song
Jonathan
J
Kim
Sanghyeon
S
Sabunciyan
Sarven
S
Diglisic
Suad
S
Yolken
Robert H
RH
Knable
Michael B
MB
Torrey
E Fuller
EF
Webster
Maree J
MJ
D000368:Aged; D001714:Bipolar Disorder / Q000235:genetics; D002102:Cadaver; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000145:classification / Q000235:genetics; D008668:Metallothionein / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000592:standards; D018579:Patient Selection; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011180:Postmortem Changes; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011618:Psychotic Disorders / Q000145:classification / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D012559:Schizophrenia / Q000145:classification / Q000235:genetics
D012333:RNA, Messenger; D008668:Metallothionein