Fibroblast Growth Factors and Their Receptors in Major Depressive Disorder: A Scoping Review of Translational Research

Major depressive disorder (MDD) is a complex psychiatric condition whose pathophysiology extends beyond the classic monoamine hypothesis, involving impaired neuroplasticity, neuroinflammation, HPA axis dysregulation, and altered neurotrophic signaling. The fibroblast growth factor (FGF) system, comprising ligands and their receptors (FGFRs), has emerged as a key candidate regulator of these processes. This scoping review qualitatively synthesizes current clinical, postmortem, and preclinical evidence on the role of the FGF system in MDD and antidepressant response. A structured literature search according to PRISMA-ScR was conducted in PubMed/MEDLINE and Scopus without date restrictions. Eligible studies included human (clinical, postmortem), preclinical, and translational data investigating FGF/FGFR expression, signaling, manipulation, or peripheral biomarker associations in the context of depression or antidepressant action. Of 287 unique records screened, 68 met the inclusion criteria; together with 11 studies identified through backward citation searching, 79 studies were included in the qualitative synthesis. This synthesis outlines a bidirectional role for the fibroblast growth factor (FGF) system in major depressive disorder (MDD). Rather than acting as a uniform pathway, different FGF ligands exert opposing regulatory effects on mood, neuroplasticity, and stress responses. FGF-2 exerts protective and neurotrophic effects, while factors like FGF-9 act as endogenous prodepressants. Although circulating biomarkers show heterogeneity, central FGF/FGFR signaling represents a promising target for novel therapeutic strategies and personalized treatment approaches in MDD.