Association Between BDNF Gene Variant Rs6265 and the Severity of Depression in Antidepressant Treatment-Free Depressed Patients.

blood levels brain derived neurotrophic factor genotypes major depressive disorder prolactin rs6265

Journal

Frontiers in psychiatry
ISSN: 1664-0640
Titre abrégé: Front Psychiatry
Pays: Switzerland
ID NLM: 101545006

Informations de publication

Date de publication:
2020
Historique:
received: 08 05 2019
accepted: 13 01 2020
entrez: 3 3 2020
pubmed: 3 3 2020
medline: 3 3 2020
Statut: epublish

Résumé

Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity, and its dysregulation has been associated with the pathogenesis of mood and anxiety disorders. Prolactin (PRL) is a pituitary hormone which is also produced as a cytokine by immune cells and could be a neurotrophic factor regulating the functional activity of stress-related mechanisms. To investigate the possible relationship between depressive state and BDNF and PRL genotypes or levels with special reference to severity of depression. Participants of 18-70 years with a clinical diagnosis of depressive disorder of at least moderate severity were included. These patients had not been treated with antidepressant drugs before admission to hospital during the preceding period of the last 6 months, and 54.5% had never been treated with antidepressant drugs during their entire life. The DNA was genotyped for rs1341239 within the prolactin and for rs6265, rs7124442, and rs11030104 within the BDNF gene. Rs11030104 violated the Hardy-Weinberg equilibrium distribution and was excluded from further analyses. BDNF and prolactin concentration was measured in serum by MAGPIX multiplex analyzer (Luminex, USA) using MILLIPLEX A total of 186 depressed patients (of which 169 were women) and 94 healthy controls (67 women) were genotyped. After excluding subjects without genetic information on all three study SNPs, 217 remained of whom 138 suffered from depression. Within depressed patients we observed an association of rs6265 with HAMD-17: mean difference (MD) 2.33 (95%CI 0.49; 4.16; We observed a significant association between BDNF gene variant rs6265 and the severity of depression in newly admitted, antidepressant treatment-free, depressed patients. Actual PRL and BDNF levels were not elevated sufficiently in depressed patients to reach statistical significance and were not associated with the studied genotypes.

Sections du résumé

BACKGROUND BACKGROUND
Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity, and its dysregulation has been associated with the pathogenesis of mood and anxiety disorders. Prolactin (PRL) is a pituitary hormone which is also produced as a cytokine by immune cells and could be a neurotrophic factor regulating the functional activity of stress-related mechanisms.
AIM OBJECTIVE
To investigate the possible relationship between depressive state and BDNF and PRL genotypes or levels with special reference to severity of depression.
METHODS METHODS
Participants of 18-70 years with a clinical diagnosis of depressive disorder of at least moderate severity were included. These patients had not been treated with antidepressant drugs before admission to hospital during the preceding period of the last 6 months, and 54.5% had never been treated with antidepressant drugs during their entire life. The DNA was genotyped for rs1341239 within the prolactin and for rs6265, rs7124442, and rs11030104 within the BDNF gene. Rs11030104 violated the Hardy-Weinberg equilibrium distribution and was excluded from further analyses. BDNF and prolactin concentration was measured in serum by MAGPIX multiplex analyzer (Luminex, USA) using MILLIPLEX
RESULTS RESULTS
A total of 186 depressed patients (of which 169 were women) and 94 healthy controls (67 women) were genotyped. After excluding subjects without genetic information on all three study SNPs, 217 remained of whom 138 suffered from depression. Within depressed patients we observed an association of rs6265 with HAMD-17: mean difference (MD) 2.33 (95%CI 0.49; 4.16;
CONCLUSION CONCLUSIONS
We observed a significant association between BDNF gene variant rs6265 and the severity of depression in newly admitted, antidepressant treatment-free, depressed patients. Actual PRL and BDNF levels were not elevated sufficiently in depressed patients to reach statistical significance and were not associated with the studied genotypes.

Identifiants

pubmed: 32116853
doi: 10.3389/fpsyt.2020.00038
pmc: PMC7028755
doi:

Types de publication

Journal Article

Langues

eng

Pagination

38

Informations de copyright

Copyright © 2020 Losenkov, Mulder, Levchuk, Vyalova, Loonen, Bosker, Simutkin, Boiko, Bokhan, Wilffert, Hak, Schmidt and Ivanova.

Références

Am J Med Genet B Neuropsychiatr Genet. 2013 Jan;162B(1):61-70
pubmed: 23184535
Front Endocrinol (Lausanne). 2016 Mar 30;7:25
pubmed: 27065946
World J Biol Psychiatry. 2013 Dec;14(8):583-9
pubmed: 22047184
Schizophr Res. 2017 Apr;182:110-114
pubmed: 27776952
Prog Neuropsychopharmacol Biol Psychiatry. 2013 Aug 1;45:183-94
pubmed: 23733030
Biomark Med. 2015;9(3):277-97
pubmed: 25731213
Neurosci Biobehav Rev. 2016 Sep;68:218-233
pubmed: 27236043
J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57
pubmed: 9881538
Am J Med Genet B Neuropsychiatr Genet. 2008 Sep 5;147B(6):814-21
pubmed: 18205169
J Affect Disord. 2013 Sep 5;150(2):384-8
pubmed: 23759278
Asia Pac Psychiatry. 2014 Sep;6(3):241-51
pubmed: 25231750
Mol Psychiatry. 2010 Mar;15(3):260-71
pubmed: 18852698
J Clin Invest. 2003 Jan;111(2):275-83
pubmed: 12531884
Behav Brain Funct. 2016 Jun 06;12(1):17
pubmed: 27267954
Trends Biotechnol. 1995 Jun;13(6):217-27
pubmed: 7598845
Am J Med Genet B Neuropsychiatr Genet. 2012 Jul;159B(5):560-6
pubmed: 22610920
Lupus. 2001;10(10):676-83
pubmed: 11721693
Curr Mol Pharmacol. 2010 Jan;3(1):12-29
pubmed: 20030625
Somat Cell Mol Genet. 1989 May;15(3):203-13
pubmed: 2567059
BMC Med. 2014 Jan 16;12:7
pubmed: 24433458
Front Behav Neurosci. 2015 Dec 21;9:329
pubmed: 26733829
J Neuroendocrinol. 2012 Jul;24(7):977-90
pubmed: 22420298
J Neurol Neurosurg Psychiatry. 1960 Feb;23:56-62
pubmed: 14399272
Expert Rev Neurother. 2014 Jan;14(1):51-65
pubmed: 24308275
Front Hum Neurosci. 2016 Nov 10;10:571
pubmed: 27891086
EMBO J. 1982;1(5):549-53
pubmed: 7188352
Acta Endocrinol (Copenh). 1991 Dec;125(6):621-7
pubmed: 1789057
Aust N Z J Obstet Gynaecol. 2011 Aug;51(4):321-4
pubmed: 21806583
J Affect Disord. 2018 Feb;227:226-235
pubmed: 29102837
J Clin Endocrinol Metab. 1998 Mar;83(3):761-4
pubmed: 9506722
Science. 1981 May 15;212(4496):815-6
pubmed: 7221563
J Psychiatr Res. 2017 Nov;94:208-217
pubmed: 28756290

Auteurs

Innokentiy S Losenkov (IS)

Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia.

Nathaniël J V Mulder (NJV)

Unit of PharmacoTherapy, -Epidemiology & -Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands.

Lyudmila A Levchuk (LA)

Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia.

Natalya M Vyalova (NM)

Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia.

Anton J M Loonen (AJM)

Unit of PharmacoTherapy, -Epidemiology & -Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands.
Policy Office for Quality and Innovation of Care (BZI), GGZ Westelijk Noord-Brabant, Halsteren, Netherlands.

Fokko J Bosker (FJ)

University Centre for Psychiatry, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands.

German G Simutkin (GG)

Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia.

Anastasiia S Boiko (AS)

Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia.

Nikolay A Bokhan (NA)

Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia.
Department of Psychotherapy and Psychological Counseling, National Research Tomsk State University, Tomsk, Russia.
Department of Psychiatry, Addictology and Psychotherapy, Siberian State Medical University, Tomsk, Russia.

Bob Wilffert (B)

Unit of PharmacoTherapy, -Epidemiology & -Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands.
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

Eelko Hak (E)

Unit of PharmacoTherapy, -Epidemiology & -Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands.

Amand F Schmidt (AF)

Unit of PharmacoTherapy, -Epidemiology & -Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands.

Svetlana A Ivanova (SA)

Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia.
Department of Psychiatry, Addictology and Psychotherapy, Siberian State Medical University, Tomsk, Russia.
Division for Control and Diagnostics, School of Non-Destructive Testing & Security, National Research Tomsk Polytechnic University, Tomsk, Russia.

Classifications MeSH