Ajaykumar N Sharma1, Bruno Fernando Borges da Costa e Silva2, Jair C Soares3, André F Carvalho4, Joao Quevedo5. 1. Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA; Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA. 2. Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA. 3. Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA. 4. Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil. 5. Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA; Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA; Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA; Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil. Electronic address: Joao.L.DeQuevedo@uth.tmc.edu.
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. Published by Elsevier B.V.
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 MDDpatients versus controls. In contrast, IGF-1 levels in MDDpatients compared to controls were discrepant across studies. Finally, most studies reported high peripheral VEGF levels and mRNA expression in MDDpatients compared to healthy controls. CONCLUSIONS:GDNF, IGF-1 and VEGF levels and their mRNA expression appear to be differentially altered in MDDpatients compared to healthy individuals, indicating that these molecules might play an important role in the pathophysiology of depression and antidepressant action of therapeutic interventions. Published by Elsevier B.V.
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