Treatment resistant depression: A case of Muenke syndrome

Major depressive disorder is a complex neuropsychiatric disorder and one of the leading causes of disability in developed countries. Treatment-resistant depression is defined as the failure of at least two adequate treatment trials. The Muenke Syndrome is an autosomal dominant disorder caused by a mutation of the fibroblast growth factor receptor 3 (FGFR3). The fibroblast growth factor (FGF) family has often been implicated in mood disorders in the literature. We present here the case of a patient with a treatment-resistant depression and a concomitant Muenke Syndrome. We propose a relationship between the two pathologies as the expression of the FGF family has been shown to be dysregulated in depressed humans, post-mortem depressed human's brains and rodent's models of depression and anxiety. In particular, FGFR3 and its major ligand, FGF9, had been shown to be down-regulated and up-regulated, respectively, in cortical areas implicated in mood disorders. Since the FGF family plays a key role in neurodevelopment and neuroplasticity, among others things, a genetic mutation in a member of the family, such as FGFR3, could lead to depressive symptoms, as in our reported case. The implication is that the FGF family may be an important target for the treatment of neuropsychiatric disorders. We also conclude that depressive symptoms should be investigated in cases of Muenke Syndrome, as FGF dysregulation in depressed patients.