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

• Published in: Journal of affective disorders Vol. 197; pp. 9 - 20
• Main Authors: Sharma, Ajaykumar N., da Costa e Silva, Bruno Fernando Borges, Soares, Jair C., Carvalho, André F., Quevedo, Joao
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2016
• Subjects: Antidepressive Agents - therapeutic use; Biomarker; Biomarkers - metabolism; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - metabolism; Depressive Disorder, Major - physiopathology; Female; GDNF; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Humans; IGF-1; Insulin-Like Growth Factor I - metabolism; Major depressive disorder; Male; Neurorophin; Psychiatry; Trophic factors; Vascular Endothelial Growth Factor A - metabolism; VEGF; GH; BD; USA; Biomarker; BDNF; GFR α1; VEGF; IGF-1; ICD; MDD; Major depressive disorder; YLD; SSRI; GDNF; IGF-IR; ECS; SNRI; Neurorophin; CSF; GDS; TGF-β; HDRS; Trophic factors; DSM; GDNF-family receptors α1; United States of America; Insulin-like growth factor-1; Selective serotonin reuptake inhibitors; Cerebrospinal fluid; Serotonin–norepinephrine reuptake inhibitors; Brain derived neurotrophic factor; Vascular endothelial growth factor; Tyrosine kinase receptor; Major Depressive Disorder; International Classification of Diseases; Glial cell line-derived neurotrophic factor; Electroconvulsive therapy; Years Lost due to Disability; Diagnostic and Statistical Manual; Bipolar Disorder; Hamilton Depression Rating Scale; Transforming growth factor-β; Geriatric Depression Scale; Growth hormone
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2016.02.067

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. 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. 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. 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. 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. •In general, MDD patients had low GDNF mRNA and protein levels.•There is an ambiguity about the role of IGF-1 in MDD.•Studies also suggest high VEGF levels in MDD patients.