Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-29T19:12:28.726Z Has data issue: false hasContentIssue false
  • English
  • Français

Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) levels in post-mortem brain tissue from patients with depression compared to healthy individuals – a proof of concept study

Published online by Cambridge University Press:  23 March 2020

A. Sheldrick ,
S. Camara ,
M. Ilieva ,
P. Riederer  and
T.M. Michel
A. Sheldrick
Affiliation:
Department Psychiatry Odense, Psychiatry in the Region of Southern Denmark, J.B. Winslowsvej 20, 5000Odense C, Denmark
S. Camara
Affiliation:
Clinical Neurochemistry, Department Psychiatry and Psychotherapy, University Hospital Würzburg, Fürchsleinstr. 15, 97080Würzburg, Germany
M. Ilieva*
Affiliation:
Department of Psychiatry, Institute for Clinical Research, University of Southern Denmark, J.B. Winslowsvej 19, 5000Odense C, Denmark
P. Riederer
Affiliation:
Department Psychiatry Odense, Psychiatry in the Region of Southern Denmark, J.B. Winslowsvej 20, 5000Odense C, Denmark Clinical Neurochemistry, Department Psychiatry and Psychotherapy, University Hospital Würzburg, Fürchsleinstr. 15, 97080Würzburg, Germany Department of Psychiatry, Institute for Clinical Research, University of Southern Denmark, J.B. Winslowsvej 19, 5000Odense C, Denmark Department Neurobiology, Instiute for Molecular Medicine, 5000Odense C, Denmark Center for applied Neuroscience, BRIDGE, Odense University Hospital, Psychiatry in the Region of Southern Denmark, University of Southern Denmark, 5000Odense C, Denmark
T.M. Michel
Affiliation:
Department Psychiatry Odense, Psychiatry in the Region of Southern Denmark, J.B. Winslowsvej 20, 5000Odense C, Denmark Department of Psychiatry, Institute for Clinical Research, University of Southern Denmark, J.B. Winslowsvej 19, 5000Odense C, Denmark Department Neurobiology, Instiute for Molecular Medicine, 5000Odense C, Denmark Center for applied Neuroscience, BRIDGE, Odense University Hospital, Psychiatry in the Region of Southern Denmark, University of Southern Denmark, 5000Odense C, Denmark
*
* Corresponding author. Department Psychiatry, Odense, Institute for Clinical Research, University of Southern Denmark, J.B. Winslowsvej 20, 5000 Odense C, Denmark. E-mail address:[email protected] (M. Ilieva).
Get access

Abstract

The neurotrophic factors (NTF) hypothesis of depression was postulated nearly a decade ago and is nowadays widely acknowledged. Previous reports suggest that cerebral concentrations of NTF may be reduced in suicide victims who received minimal or no antidepressant pharmacotherapy. Recent evidence suggests that antidepressant treatment may improve or normalise cerebral concentrations of neurotrophic factors. Therefore, we examined the concentration of brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) in different brain regions (cortex, cingulate gyrus, thalamus, hippocampus, putamen and nucleus caudatus) of 21 individuals – 7 patients of which 4 patients with major depressive disorder (MDD) and overall age 86.8 ± 5 years who received antidepressant pharmacotherapy (selective serotonin re-uptake inhibitors [SSRI]; tricyclic antidepressants [TCA]), 3 patients with MDD without antidepressant treatment and overall age 84.3 ± 5 years versus 14 unaffected subjects at age 70.3 ± 13.8. We detected significant elevation of BDNF (parietal cortex) and NT3 (parietal, temporal and occipital cortex, cingulate gyrus, thalamus, putamen and nucleus caudatus regions) in MDD patients who received antidepressant medication compared to MDD untreated patients and controls. Moreover, we detected a significant decrease of NT3 levels in the parietal cortex of patients suffering from MDD non-treated patients without treatment compared to healthy individuals. Although the limited statistical power due to the small sample size in this proof of concept study corroborates data from previous studies, which show that treatment with antidepressants mediates alterations in neuroplasticity via the action of NTF. However, more research using post-mortem brain tissue with larger samples needs to be carried out as well as longitudinal studies to further verify these results.

Keywords

Affective disordersDepressionPsychiatryMolecular biologyPsychopharmacologyAntidepressants
Type
Original article
Information
European Psychiatry , Volume 46 , October 2017 , pp. 65 - 71
Copyright
Copyright © European Psychiatric Association 2017

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Duman, RSHeninger, GRNestler, EJA molecular and cellular theory of depression. Arch Gen Psychiatry 1997;54:597–606.CrossRefGoogle Scholar
Altar, CACriden, MRLindsay, RMDiStefano, PSCharacterization and topography of high-affinity 125I-neurotrophin-3 binding to mammalian brain. J Neurosci 1993;13:733–743.CrossRefGoogle ScholarPubMed
Vaidya, VADuman, RSDepresssion-emerging insights from neurobiology. Br Med Bull 2001;57:61–79.CrossRefGoogle ScholarPubMed
Roceri, MCirulli, FPessina, CPeretto, PRacagni, GRiva, MAPostnatal repeated maternal deprivation produces age-dependent changes of brain-derived neurotrophic factor expression in selected rat brain regions. Biol Psychiatry 2004;55:708–714.CrossRefGoogle ScholarPubMed
Zhou, CZhong, JZou, BFang, LChen, JDeng, X, et al.Meta-analyses of comparative efficacy of antidepressant medications on peripheral BDNF concentration in patients with depression. PLoS One 2017;12(2):e0172270.CrossRefGoogle Scholar
Maisonpierre, PCBelluscio, LFriedman, BAlderson, RFWiegand, SJFurth, ME, et al.NT3, BDNF and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression. Neuron 1990;5:501–509.CrossRefGoogle Scholar
Thonen, HNeurotrophins and neuronal plasticity. Science 1995;270:593–598.CrossRefGoogle Scholar
Duman, RSMalberg, JNakagawa, SD'Sa, CNeuronal plasticity and survival in mood disorders. Biol Psychiatry 2000;48:732–739.CrossRefGoogle ScholarPubMed
Duman, RSMonteggia, LMA neurotrophic model for stress-related mood disorders. Biol Psychiatry 2006;59:1116–1127.CrossRefGoogle ScholarPubMed
Siuciak, JALewis, DRWiegand, SJLindsay, RMAntidepressant-like effect of brain-derived neurotrophic factor (BDNF). Pharmacol Biochem Behav 1997;56(1): 131–137.CrossRefGoogle Scholar
Frank, LWiegand, SJSiuciak, JALindsay, RMRudge, JSEffects of BDNF infusion on the regulation of TrkB protein and message in adult rat brain. Exp Neurol 1997;145:62–70.CrossRefGoogle ScholarPubMed
Krishnan, VNestler, EJThe molecular neurobiology of depression. Nature 2008;455:894–902.CrossRefGoogle Scholar
Karege, FPerret, GBondolfi, GSchwald, MBertschy, GAubry, JMDecreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 2002;109:143–148.CrossRefGoogle ScholarPubMed
Aydemir, ODeveci, ATaneli, FThe effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:261–265.CrossRefGoogle ScholarPubMed
Shimizu, EHashimoto, KOkamura, NKoike, KKomatsu, NKumakiri, C, et al.Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 2003;54:70–75.CrossRefGoogle ScholarPubMed
Gonul, ASAkdeniz, FTaneli, FDonat, OEker, CVahip, SEffect of treatment on serum brain-derived neurotrophic factor levels in depressed patients. Eur Arch Psychiatry Clin Neurosci 2005;255:381–386.CrossRefGoogle ScholarPubMed
Chen, BDowlatshahi, DMacQueen, GMWang, JFYoung, LTIncreased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry 2001;50:260–265.CrossRefGoogle ScholarPubMed
Karege, FVaudan, GSchwald, MPerroud, NLa Harpe, RNeurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs. Brain Res Mol Brain Res 2005;136:29–37.CrossRefGoogle ScholarPubMed
Angelucci, FAloe, LJiménez-Vasquez, PMathé, AAElectroconvulsive stimuli alter the regional concentrations of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor in adult rat brain. J ECT 2002;18:138–143.CrossRefGoogle ScholarPubMed
Pinna, MManchia, MOppo, RScano, FPillai, GLoche, AP, et al. Clinical and biological predictors of response to electroconvulsive therapy (ECT): a review. Neurosci Lett 2016. http://dx.doi.org/10.1016/j.neulet.2016.10.047.CrossRefGoogle Scholar
Keller, SSarchiapone, MZarrilli, FVidetic, AFerraro, ACarli, V, et al.Increased BDNF promoter methylation in the Wernicke area of suicide subjects. Arch Gen Psychiatry 2010;67(3): 258–267. doi:10.1001/archgenpsychiatry.2010.9.CrossRefGoogle ScholarPubMed
Kang, HJKim, JMLee, JYKim, SYBae, KYKim, SW, et al.BDNF promoter methylation and suicidal behavior in depressive patients. J Affect Disord 2013;151(2): 679–685. http://dx.doi.org/10.1016/j.jad.2013.08.001.CrossRefGoogle ScholarPubMed
Januar, VAncelin, M.-L.Ritchie, M.L.Saffery, KRyan, RJBDNF promoter methylation and genetic variation in late-life depression. Transl Psychiatry 2015;5:e619. http://dx.doi.org/10.1038/tp.2015.114.CrossRefGoogle ScholarPubMed
Keller, SSarchiapone, MZarrilli, FTomaiuolo, RCarli, VAngrisano, T, et al.TrkB gene expression and DNA methylation state in Wernicke area does not associate with suicidal behavior. J Affect Disord 2011;135(400): 40410. doi:1016/j.jad.2011.07.003.CrossRefGoogle Scholar
Chen, ESErnst, CTurecki, GThe epigenetic effects of antidepressant treatment on human prefrontal cortex BDNF expression. Int J Neuropsychopharmacol 2011;14:427–429. http://dx.doi.org/10.1017/S1461145710001422.CrossRefGoogle ScholarPubMed
Lopez, JPMamdani, FLabonte, BBeaulieu, MMYang, JPBerlim, MT, et al.Epigenetic regulation of BDNF expression according to antidepressant response. Mol. Psychiatry 2013;18:398–399.CrossRefGoogle ScholarPubMed
Stenz, LZewdie, SLaforge-Escarra, TPrados, JLa Harpe, RDayer, A, et al.BDNF promoter I methylation correlates between post-mortem human peripheral and brain tissues. Neurosci Res 2015;91:1–7.CrossRefGoogle ScholarPubMed
Guilloux, JPDouillard-Guilloux, GKota, RWang, XGardier, AMMartinowich, K, et al. Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression. Mol Psychiatry 2011. http://dx.doi.org/10.1038/mp.2011.113.CrossRefGoogle Scholar
Gsell, WLange, KWPrfueffer, RHeckers, SHeinsen, HSenitz, D, et al.How to run a brain bank. A report from the Austro-Germanian brain bank. J Neural Trans Suppl 1993;39:31–70.Google Scholar
Lowry, OHRosebrough, NJFarr, ALRandall, RJProtein measurement with the folin phol reagent. J Biol Chem 1951;193:265–276.Google Scholar
Gervasoni, NAubry, JMBondolfi, GOsiek, CSchwald, MBertschy, G, et al.Partial normalization of serum brain-derived neurotrophic factor in remitted patients after a major depressive episode. Neuropsychobiology 2005;51:234–238.CrossRefGoogle ScholarPubMed
Jevtović, SKarlović, DMihaljević-Peleš, AŠerić, VVrkić, NJakšić, NSerum brain-derived neurotrophic factor (BDNF): the severity and symptomatic dimensions of depression. Psychiatr Danub 2011;23:363–369.Google Scholar
Dreimüller, NSchlicht, KFWagner, SPeetz, DBorysenko, LHiemke, C, et al.Early reactions of brain-derived neurotrophic factor in plasma (pBDNF) and outcome to acute antidepressant treatment in patients with major depression. Neuropharmacology 2012;62:264–269.CrossRefGoogle ScholarPubMed
Haile, CNMurrough, JWIosifescu, DVChang, LCAl Jurdi, RKFoulkes, A, et al.Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression. Int J Neuropsychopharmacol 2014;17:331–336.CrossRefGoogle ScholarPubMed
Papakostas, GIShelton, RCKinrys, GHenry, MEBakow, BRLipkin, SH, et al.Assessment of a multi-assay, serum-based biological diagnostic test for major depressive disorder: a pilot and replication study. Mol Psychiatry 2013;18:332–339.CrossRefGoogle ScholarPubMed
Nibuya, MMorinobu, SDuman, RSRegulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 1995;15:7539–7547.CrossRefGoogle ScholarPubMed
Angelucci, FAloe, LVasquez, PJMathé, AAMapping the differences in the brain concentration of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in an animal model of depression. Neuroreport 2000;11:1369–1373.CrossRefGoogle Scholar
Pandey, GNRen, XRizavi, HSConley, RRRoberts, RCDwivedi, YBrain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims. Int J Neuropsychopharmacol 2008;11:1047–1061.CrossRefGoogle ScholarPubMed
Michel, TMFrangou, SCamara, SThiemeyer, DJecel, JTatschner, T, et al.Altered glial cell line-derived neurotrophic factor (GDNF) concentrations in the brain of patients with depressive disorder. A comparative post-mortem study. European Psychiatry 2008;23:413–420.CrossRefGoogle ScholarPubMed
Michel, TMThome, JNara, KMartin, DCamara, SWeijers, HG, et al.The role of oxidative stress in the pathogenesis of schizophrenic psychoses – superoxide dismutase (SOD)-coenzyme concentrations in post-mortem brain tissue of schizophrenic patients. J Neural Transm 2004;111:1191–1201.Google Scholar
Michel, TMFrangou, SThiemeyer, DCamara, SZoechling, RJecel, J, et al.Evidence for oxidative stress in the frontal cortex in patients with recurrent depressive disorder – a post-mortem study. Psychiatry Res 2007;151:145–150.CrossRefGoogle Scholar
Michel, TMFrangou, SCamara, STatschner, TSheldrick, AJRiederer, P, et al.Evidence for increased oxidative stress in the thalamus and in the putamen in patients with recurrent depressive disorder – a post-mortem investigation. World Journal Biol Psychiatry 2008;12:1–7.CrossRefGoogle Scholar
Michel, TMSheldrick, AJCamara, SSchneider, FGrünblatt, ERiederer, PAlteration of the pro-oxidant xanthine oxidase (XO) in the thalamus and the cerebral cortex of patients with schizophrenia. World J Biol Psychiatry 2011;12(8): 588–597.CrossRefGoogle ScholarPubMed
Blugeot, ARivat, CBouvier, EMolet, JMouchard, AZeau, B, et al.Vulnerability to depression: from brain neuroplasticity to identification of biomarkers. J Neurosci 2011;31:12889–12899.CrossRefGoogle ScholarPubMed
Ye, YWang, GWang, HWang, XBrain-derived neurotrophic factor (BDNF) infusion restored astrocytic plasticity in the hippocampus of a rat model of depression. Neurosci Lett 2011;503:15–19.CrossRefGoogle Scholar
Cole, JCostafreda, SGMcGuffin, PFu, CHHippocampal atrophy in first episode depression: a meta-analysis of magnetic resonance imaging studies. J Affect Disord 2011;134:483–487.CrossRefGoogle ScholarPubMed
Gerritsen, LTendolkar, IFranke, BVasquez, AAKooijman, SBuitelaar, J, et al.BDNF Val66Met genotype modulates the effect of childhood adversity on subgenual anterior cingulate cortex volume in healthy subjects. Mol Psychiatry 2012;17:597–603.CrossRefGoogle ScholarPubMed
Warner-Schmidt, JLDuman, RSHippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus 2006;16:239–249.CrossRefGoogle ScholarPubMed
Drzyzga, ŁRMarcinowska, AObuchowicz, EAntiapoptotic and neurotrophic effects of antidepressants: a review of clinical and experimental studies. Brain Res Bull 2009;79:248–257.CrossRefGoogle ScholarPubMed
Thome, JNara, KFoley, PMichel, TGsell, WRetz, W, et al.CNTF genotypes: influence on choline acetyltransferase (ChAT) and acetylcholine esterase (AChE) activities and neurotrophin 3 (NT3) concentration in human post mortem brain tissue. J Brain Res 1997;38:443–451.Google ScholarPubMed
Supplementary material: File

Sheldrick et al. supplementary material

Table S1
Download Sheldrick et al. supplementary material(File)
File 43 KB
Supplementary material: File

Sheldrick et al. supplementary material

Table S2
Download Sheldrick et al. supplementary material(File)
File 42.5 KB
Submit a response

Comments

No Comments have been published for this article.