Dysregulation of Specific Growth Factor System Gene Expression in Limbic Structures of Subjects with Major Depressive Disorder.

SJ Evans; J Li; PV Choudary; H Tomita; MP Vawter; CA Turner; JF Lopez; RC Thompson; F Meng; BM Bolstad; TP Speed; RM Myers; WE Bunney; EG Jones; SJ Watson; H Akil
Society for Neuroscience 34th Annual Meeting. 2004.


Growth factor disregulation has been implicated in psychiatric illness and may contribute to malfunction of neuronal circuitry. We have previously described studies of post-mortem human brains using DNA microarray technology and real-time PCR to discover that the fibroblast growth factor (FGF) system is dysregulated in neocortical regions, including anterior cingulated cortex and dorsolateral prefrontal cortex, in subjects with major depressive disorder (MDD). Importantly, we do not find dysregulation of this system in subjects with bipolar disorder (BPD), suggesting that this may be specific for MDD. Here we report an extension of our study with the addition of more MDD and BPD subjects as well as matched controls. Furthermore, we have added more limbic structures, including amygdala and hippocampus and have discovered similar dysregulation of the FGF system in MDD subjects in these regions. Importantly, we have analyzed separately depressive subjects on antidepressant therapy and those not receiving medication to show that dysregulation of the FGF system is not likely secondary to drug treatment. In fact SSRI therapy tended to normalize expression of specific FGF system transcripts, in the direction of controls, suggesting that the FGF system might be one target of this class of drugs. The authors are members of the Pritzker Neuropsychiatric Disorders Research Consortium which is supported by the Pritzker Family Philanthropic Fund. A shared intellectual property agreement exists between the Pritzker Family Philanthropic Fund and all the universities involved, in order to encourage the development of appropriate findings for research and clinical applications.