Role of trophic factors GDNF, IGF-1 and VEGF in major depressive disorder: A comprehensive review of human studies

Abstract

Rationale The neurotrophin hypothesis of major depressive disorder (MDD) postulates that this illness results from aberrant neurogenesis in brain regions that regulates emotion and memory. Notwithstanding this theory has primarily implicated BDNF in the neurobiology of MDD. Recent evidence suggests that other trophic factors namely GDNF, VEGF and IGF-1 may also be involved. Purpose The present review aimed to critically summarize evidence regarding changes in GDNF, IGF-1 and VEGF in individuals with MDD compared to healthy controls. In addition, we also evaluated the role of these mediators as potential treatment response biomarkers for MDD. Methods A comprehensive review of original studies studies measuring peripheral, central or mRNA levels of GDNF, IGF-1 or VEGF in patients with MDD was conducted. The PubMed/MEDLINE database was searched for peer-reviewed studies published in English through June 2nd, 2015. Results Most studies reported a reduction in peripheral GDNF and its mRNA levels in MDD patients versus controls. In contrast, IGF-1 levels in MDD patients compared to controls were discrepant across studies. Finally, most studies reported high peripheral VEGF levels and mRNA expression in MDD patients compared to healthy controls. Conclusions GDNF, IGF-1 and VEGF levels and their mRNA expression appear to be differentially altered in MDD patients compared to healthy individuals, indicating that these molecules might play an important role in the pathophysiology of depression and antidepressant action of therapeutic interventions.

Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression

“…It is a member of the transforming growth factor β (TGF-β) superfamily and is important for neuronal survival especially for dopaminergic and serotonergic neurons. It binds to the GDNF-family receptors α1 (GFRα1) activating tyrosine kinase signaling (Sharma et al 2016). …”

“…Only a few clinical studies examined the role of GDNF in MDD, and contrasting findings between brain and blood expression are reported (Sharma et al 2016). A recent post-mortem brain analysis showed an increase of (GDNF) expression in the parietal cortex of MDD patients (Michel et al 2008).…”

Epigenetic Regulation of the Promotor Region of Vascular Endothelial Growth Factor-A and Nerve Growth Factor in Opioid-Maintained Patients

“…Its impact in psychiatric diseases has been shown, for example, in major depression disorders (MDD), as VEGF levels and respective mRNA expression are differentially altered in depressive patients compared to those in healthy individuals. Most studies report higher VEGF serum levels and mRNA expression in patients with MDD compared to similar levels in healthy controls, indicating that these molecules might play an important role in its pathophysiology [11]. In schizophrenia, VEGF plasma levels were significantly increased after antipsychotic medication [12].…”

The Role of Neuropeptide Y mRNA Expression Level in Distinguishing Different Types of Depression

“…Preclinical and clinical studies suggest that many mechanisms are involved in this disorder including neurotrophic signaling, cellular plasticity and activation of the hypothalamic-pituitary-adrenal (HPA) axis (Spalletta et al, 2006; Loubinoux et al, 2012). In the aspect of the neurotrophic and neurochemical factors, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and vascular endothelial growth factor were proved to play an important role in the pathophysiology of depression and antidepressant action of therapeutic interventions (Sharma et al, 2016). In addition, Neuropeptide Y (NPY), a 36-amino acid peptide, is widely distributed in the central and peripheral nervous systems such as most cortical areas, hippocampus, amygdala, olfactory bulb and spinal cord of the rat and human brain (Dumont et al, 1992).…”