Fibroblast growth factors 2 and 9 may act as molecular organizers in anterior cingulate cortex and hippocampus to mediate circuit function in MDD
Aurbach EL, Hagenauer MH, Prater KE, Bunney WE, Myers RM, Barchas JD, Schatzberg AF, Li JZ, Meng F, Watson SJ, Akil H
Society for Neuroscience. 2016.
The neurotrophic hypothesis posits that changes in the expression and function of growth factors in the brain underlie the pathophysiology of Major Depressive Disorder (MDD). Previous work implicated two members of the fibroblast growth factor (FGF) system in MDD and affective dysregulation in animal models. We have previously shown that FGF2 as an endogenous anxiolytic and antidepressant molecule whose expression is downregulated in the depressed brain, while FGF9 has anxiogenic and pro-depressant properties and is upregulated in the depressed brain. However, it is unknown if FGF2 and/or FGF9 act in isolation to mediate these effects or if they are part of a larger ensemble of genes which become selectively dysregulated in MDD. Because we hypothesized that relative levels of FGF2 and FGF9 might be important to MDD pathophysiology, we examined diagnosis-specific relationships in expression between FGF2, FGF9, and FGF receptors, and we found regional patterns of alteration with MDD. In the anterior cingulate cortex, correlations between FGF family members were lost in MDD, while in the hippocampus, new relationships emerged. These changes were related to alterations in correlated gene expression of transcripts related to fundamental biology and circuit function, supporting the hypothesis that FGF2 and FGF9 may influence affect by acting as molecular organizers whose effects become dysregulated during MDD. Future studies will validate these findings in other datasets and on other platforms, and explore the possibility that coordinate dysregulation of FGF2 and FGF9 with an ensemble of other genes can serve as a biological signature of MDD.