Dysregulation of the fibroblast growth factor system in major depression.
In this report we describe findings that imply dysregulation of several fibroblast growth factor (FGF) system transcripts in frontal cortical regions of brains from human subjects with major depressive disorder (MDD). This altered gene expression was discovered by microarray analysis of frontal cortical tissue from MDD, bipolar, and nonpsychiatric control subjects and was verified by quantitative real-time PCR analysis and, importantly, in a separate cohort of MDD subjects. Furthermore, we show, through a separate analysis of specific serotonin reuptake inhibitor (SSRI)-treated and non-SSRI-treated MDD subjects that the observed changes in expression of FGF transcripts are not secondary to drug treatment. Rather, changes in specific FGF transcripts are attenuated by SSRIs and may thus be partially responsible for the mechanism of action of these drugs. We also make available the gene-expression profile of all of the other growth factors and growth factor receptors detected in these postmortem samples.
Department of Psychiatry and Mental Health Research Institute, University of Michigan, Ann Arbor, MI 48109, USA. evanssi@umich.edu
S J
SJ
Evans
P V
PV
Choudary
C R
CR
Neal
J Z
JZ
Li
M P
MP
Vawter
H
H
Tomita
J F
JF
Lopez
R C
RC
Thompson
F
F
Meng
J D
JD
Stead
D M
DM
Walsh
R M
RM
Myers
W E
WE
Bunney
S J
SJ
Watson
E G
EG
Jones
H
H
Akil
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use
D005346:Fibroblast Growth Factors; D017367:Selective Serotonin Reuptake Inhibitors