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

doi:10.1016/j.jad.2016.02.067

Review

. 2016 Jun:197:9-20.

doi: 10.1016/j.jad.2016.02.067. Epub 2016 Mar 2.

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

Ajaykumar N Sharma¹, Bruno Fernando Borges da Costa e Silva², Jair C Soares³, André F Carvalho⁴, Joao Quevedo⁵

Affiliations

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.

PMID: 26956384
PMCID: PMC4837031
DOI: 10.1016/j.jad.2016.02.067

Review

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

Ajaykumar N Sharma et al. J Affect Disord. 2016 Jun.

. 2016 Jun:197:9-20.

doi: 10.1016/j.jad.2016.02.067. Epub 2016 Mar 2.

Authors

Ajaykumar N Sharma¹, Bruno Fernando Borges da Costa e Silva², Jair C Soares³, André F Carvalho⁴, Joao Quevedo⁵

Affiliations

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.

PMID: 26956384
PMCID: PMC4837031
DOI: 10.1016/j.jad.2016.02.067

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.

Keywords: Biomarker; GDNF; IGF-1; Major depressive disorder; Neurorophin; Trophic factors; VEGF.

Published by Elsevier B.V.

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References

1. Arnold SE, Xie SX, Leung YY, Wang LS, Kling MA, Han X, Shaw LM. Plasma biomarkers of depressive symptoms in older adults. Transl Psychiatry. 2012;2:e65. - PMC - PubMed
1. Bach MA, Shen-Orr Z, Lowe WL, Jr, Roberts CT, Jr, LeRoith D. Insulin-like growth factor I mRNA levels are developmentally regulated in specific regions of the rat brain. Brain Res Mol Brain Res. 1991;10(1):43–48. - PubMed
1. Berent D, Macander M, Szemraj J, Orzechowska A, Galecki P. Vascular endothelial growth factor A gene expression level is higher in patients with major depressive disorder and not affected by cigarette smoking, hyperlipidemia or treatment with statins. Acta Neurobiol Exp (Wars) 2014;74(1):82–90. - PubMed
1. Carvalho AF, Kohler CA, McIntyre RS, Knochel C, Brunoni AR, Thase ME, Berk M. Peripheral vascular endothelial growth factor as a novel depression biomarker: A meta-analysis. Psychoneuroendocrinology. 2015;62:18–26. - PubMed
1. Carvalho LA, Bergink V, Sumaski L, Wijkhuijs J, Hoogendijk WJ, Birkenhager TK, Drexhage HA. Inflammatory activation is associated with a reduced glucocorticoid receptor alpha/beta expression ratio in monocytes of inpatients with melancholic major depressive disorder. Transl Psychiatry. 2014;4:e344. - PMC - PubMed

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[1] Arnold SE, Xie SX, Leung YY, Wang LS, Kling MA, Han X, Shaw LM. Plasma biomarkers of depressive symptoms in older adults. Transl Psychiatry. 2012;2:e65. - PMC - PubMed

[2] Arnold SE, Xie SX, Leung YY, Wang LS, Kling MA, Han X, Shaw LM. Plasma biomarkers of depressive symptoms in older adults. Transl Psychiatry. 2012;2:e65. - PMC - PubMed

[3] Bach MA, Shen-Orr Z, Lowe WL, Jr, Roberts CT, Jr, LeRoith D. Insulin-like growth factor I mRNA levels are developmentally regulated in specific regions of the rat brain. Brain Res Mol Brain Res. 1991;10(1):43–48. - PubMed

[4] Bach MA, Shen-Orr Z, Lowe WL, Jr, Roberts CT, Jr, LeRoith D. Insulin-like growth factor I mRNA levels are developmentally regulated in specific regions of the rat brain. Brain Res Mol Brain Res. 1991;10(1):43–48. - PubMed

[5] Berent D, Macander M, Szemraj J, Orzechowska A, Galecki P. Vascular endothelial growth factor A gene expression level is higher in patients with major depressive disorder and not affected by cigarette smoking, hyperlipidemia or treatment with statins. Acta Neurobiol Exp (Wars) 2014;74(1):82–90. - PubMed

[6] Berent D, Macander M, Szemraj J, Orzechowska A, Galecki P. Vascular endothelial growth factor A gene expression level is higher in patients with major depressive disorder and not affected by cigarette smoking, hyperlipidemia or treatment with statins. Acta Neurobiol Exp (Wars) 2014;74(1):82–90. - PubMed

[7] Carvalho AF, Kohler CA, McIntyre RS, Knochel C, Brunoni AR, Thase ME, Berk M. Peripheral vascular endothelial growth factor as a novel depression biomarker: A meta-analysis. Psychoneuroendocrinology. 2015;62:18–26. - PubMed

[8] Carvalho AF, Kohler CA, McIntyre RS, Knochel C, Brunoni AR, Thase ME, Berk M. Peripheral vascular endothelial growth factor as a novel depression biomarker: A meta-analysis. Psychoneuroendocrinology. 2015;62:18–26. - PubMed

[9] Carvalho LA, Bergink V, Sumaski L, Wijkhuijs J, Hoogendijk WJ, Birkenhager TK, Drexhage HA. Inflammatory activation is associated with a reduced glucocorticoid receptor alpha/beta expression ratio in monocytes of inpatients with melancholic major depressive disorder. Transl Psychiatry. 2014;4:e344. - PMC - PubMed

[10] Carvalho LA, Bergink V, Sumaski L, Wijkhuijs J, Hoogendijk WJ, Birkenhager TK, Drexhage HA. Inflammatory activation is associated with a reduced glucocorticoid receptor alpha/beta expression ratio in monocytes of inpatients with melancholic major depressive disorder. Transl Psychiatry. 2014;4:e344. - PMC - PubMed

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

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

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