Gene expression profiling in postmortem prefrontal cortex of major depressive disorder.
Investigations of the molecular mechanisms underlying major depressive disorder (MDD) have been hampered by the complexity of brain tissue and sensitivity of gene expression profiling approaches. To address these issues, we used discrete microdissections of postmortem dorsolateral prefrontal cortex (DLPFC) (area 9) and an oligonucleotide (60mer) microarray hybridization procedure that increases sensitivity without RNA amplification. Mixed-effects statistical methods were used to rigorously control for medication usage in the subset of medicated depressed subjects. These analyses yielded a rich profile of dysregulated genes. Two of the most highly dysregulated genes of interest were stresscopin, a neuropeptide involved in stress responses, and Forkhead box D3 (FOXD3), a transcription factor. Secondary cell-based analysis demonstrated that stresscopin and FoxD3 are increased in neurons of DLPFC gray matter of MDD subjects. These findings identify abnormal gene expression in a discrete region of MDD subjects and contribute to further elucidation of the molecular alterations of this complex mood disorder.
Department Psychiatry, Yale University, New Haven, Connecticut 06508, USA.
Hyo Jung
HJ
Kang
David H
DH
Adams
Arthur
A
Simen
Birgitte B
BB
Simen
Grazyna
G
Rajkowska
Craig A
CA
Stockmeier
James C
JC
Overholser
Herbert Y
HY
Meltzer
George J
GJ
Jurjus
Lisa C
LC
Konick
Samuel S
SS
Newton
Ronald S
RS
Duman
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002453:Cell Cycle / Q000235:genetics; D016923:Cell Death; D002454:Cell Differentiation / Q000235:genetics; D003865:Major Depressive Disorder / Q000473:pathology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011180:Postmortem Changes; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology*; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors
C503514:FOXD3 protein, human; D051858:Forkhead Transcription Factors; D014157:Transcription Factors