Changes of Serum Concentrations of Brain-Derived Neurotrophic Factor (BDNF) during Treatment with Venlafaxine and Mirtazapine: Role of Medication and Response to Treatment

M. Deuschle; M. Gilles; B. Scharnholz; F. Lederbogen; U. E. Lang; R. Hellweg

doi:10.1055/s-0032-1321908

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2013; 46(02): 54-58
DOI: 10.1055/s-0032-1321908

Original Paper

Changes of Serum Concentrations of Brain-Derived Neurotrophic Factor (BDNF) during Treatment with Venlafaxine and Mirtazapine: Role of Medication and Response to Treatment

M. Deuschle^*

¹Faculty of Medicine Mannheim, Central Institute of Mental Health, University of Heidelberg, Germany

,

M. Gilles^*

¹Faculty of Medicine Mannheim, Central Institute of Mental Health, University of Heidelberg, Germany

,

B. Scharnholz

¹Faculty of Medicine Mannheim, Central Institute of Mental Health, University of Heidelberg, Germany

,

F. Lederbogen

¹Faculty of Medicine Mannheim, Central Institute of Mental Health, University of Heidelberg, Germany

,

U. E. Lang

²Department of Psychiatry, Campus Mitte, Charité, Berlin, Germany

,

R. Hellweg

²Department of Psychiatry, Campus Mitte, Charité, Berlin, Germany

› Author Affiliations

Abstract

Introduction:

Depression, stress and antidepressant treatment have been found to modulate the expression of brain-derived neurotrophic factor (BDNF). Recent research suggests that serum BDNF concentration is reduced in depression and that antidepressant treatment leads to an increase in serum BDNF concentration.

Methods:

We studied depressed patients receiving a randomized antidepressant treatment with either mirtazapine (n=29) or venlafaxine (n=27) for 28 days in a prospective design. Changes in the concentrations of serum neurotrophins in response to antidepressant treatment were assessed.

Results:

There was a significant “treatment” by “medication” interaction effect on BDNF serum concentrations that indicated a decline of BDNF in venlafaxine-treated patients (7.82±3.75–7.18±5.64 ng/mL), while there was an increase in mirtazapine-treated patients (7.64±6.23–8.50±5.37 ng/mL). There was a trend for a “treatment” by “remission” interaction with a favourable clinical course being related to increasing serum BDNF.

Discussion:

Changes in BDNF serum concentrations as a result of antidepressant therapy depend on the antidepressant and potentially on the clinical course.

Key words

brain-derived neurotrophic factor (BDNF) - depression - remission - antidepressant

Full Text

References

References
1 Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry 2006; 59: 1116-1127
2 Castrén E, Rantamäki T. Role of brain-derived neurotrophic factor in the aetiology of depression: implications for antidepressant treatment. CNS Drugs 2010; 24: 1-7
3 Nibuya M, Morinobu S, Duman R. Regulation of BDNF and TrkB messenger RNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neuroscience 1995; 15: 7539-7547
4 Sartorius A, Hellweg R, Litzke J et al. Correlations and discrepancies between serum and brain tissue levels of neurotrophins after electroconvulsive treatments in rats. Pharmacopsychiatry 2009; 42: 270-276
5 Shirayama Y, Chen ACH, Nakagawa S. Brain-derived neurotrophic factor produces antidepressant effects in behavioural models of depression. J Neuroscience 2002; 22: 3251-3261
6 Cooke JD, Grover LM, Spangler PR. Venlafaxine treatment stimulates expression of BDNF protein in frontal cortex and inhibits long-term potentiation in hippocampus. Neuroscience 2009; 162: 1411-1419
7 Xu HY, Chen Z, He J et al. Synergistic effects of quetiapine and venlafaxine in preventing the chronic restraint stress-induced decrease in cell proliferation and BDNF expression in rat hippocampus. Hippocampus 2006; 16: 551-559
8 Rogoz Z, Skuza G, Legutko B. Repeated treatment with mirtazapine induces brain-derived neurotrophic factor gene expression in rats. J Physiol Pharmacol 2005; 56: 661-671
9 Dias BG, Banerjee SB, Duman RS et al. Differential regulation of brain derived neurotrophic factor transcripts by antidepressant treatments in the adult rat brain. Neuropharmacol 2003; 45: 553-563
10 Russo-Neustadt AA, Alejandre H, Garcia C et al. Hippocampal brain-derived neurotrophic factor expression following treatment with reboxetine, citalopram, and physical exercise. Neuropsychopharmacology 2004; 29: 2189-2199
11 Altar CA, Whitehead RE, Chen RY et al. Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain. Biol Psychiatry 2003; 54: 703-709
12 Jacobsen JPR, Mork A. The effect of citalopram, desipramine, electroconvulsive seizures and lithium on brain-derived neurotrophic factor mRNA and protein expression in the rat brain and correlation to 5-HT and 5-HIAA levels. Brain Res 2004; 1024: 183-192
13 Schulte-Herbrüggen O, Fuchs E, Abumaria N et al. Effects of escitalopram on the regulation of brain-derived neurotrophic factor and nerve growth factor protein levels in a rat model of chronic stress. J Neurosci Res 2009; 87: 2551-2560
14 Sen S, Duman R, Sanacora G. Serum brain-derived neurotrophic factor, depression and antidepressant medications: meta-analysis and implications. Biol Psychiatry 2008; 64: 527-532
15 Molendijk ML, Bus BAA, Spinhoven P et al. Serum levels of brain-derived neurotrophic factor in major depressive disorder: state-trait issues, clinical features and pharmacological treatment. Mol Psychiatry 2011; 16: 1088-1095
16 Matrisciano F, Bonaccorso S, Ricciardi A et al. Changes in BDNF serum levels in patients with major depression disorder after 6 months treatment with sertraline, escitalopram or venlafaxine. J Psychiat Res 2008; 43: 247-254
17 Basterzi AD, Yazici K, Aslan E et al. Effects of fluoxetine and venlafaxine on serum brain derived neurotrophic factor levels in depressed patients. Prog Neuro Psychopharmacol Biol Psych 2009; 33: 281-285
18 Aydemir C, Yalcin ES, Aksaray S et al. Brain-derived neurotrophic factor (BDNF) changes in serum of depressed women. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 1256
19 Gervasoni N, Aubry JM, Bondolfi G et al. Partial normalization of serum brain-derived neurotrophic factor in remitted patients after a major depressive episode. Neuropsychobiology 2005; 51: 234-238
20 Gonul AS, Akdeniz F, Taneli F et al. Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients. Eur Arch Psych Clin Neurosci 2005; 255: 381-386
21 Piccinni A, Marazziti D, Catena M et al. Plasma and serum brain-derived neurotrophic factor (BDNF) in depressed patients during 1 year of antidepressant treatments. J Affect Disord 2008; 105: 279-283
22 Huang TL, Lee CT, Liu YL. Serum brain-derived neurotrophic factor levels in patients with major depression: effects of antidepressants. J Psychiatr Res 2007; 42: 521-525
23 Hellweg R, Ziegenhorn A, Heuser I et al. Serum concentrations of nerve growth factor and brain-derived neurotrophic factor in depressed patients before and after antidepressant treatment. Pharmacopsychiatry 2008; 41: 66-71
24 Möller HJ. Outcomes in major depressive disorder: the evolving concept of remission and its implications for treatment. W J Biol Psychiatry 2008; 9: 102-114
25 Hellweg R, Lohmann P, Huber R et al. Spatial navigation in complex and radial mazes in APP23 animals and neurotrophin signalling as a biological marker of early impairment. Learn Mem 2006; 13: 63-71
26 Ziegenhorn AA, Schulte-Herbrüggen O, Danker-Hopfe H et al. Serum neurotrophins – a study on the time course and influencing factors in a large old age sample. Neurobiol Aging 2006; 28: 1436-1445
27 Satomura E, Baba H, Nakano Y et al. Correlations between brain-derived neurotrophic factor and clinical symptoms in medicated patients with major depression. J Affect Disord 2011; 135: 232-325
28 Russo-Neustadt A, Beard RC, Cotman CW. Exercise, antidepressant medications, and enhanced brain derived neurotrophic factor expression. Neuropsychopharmacology 1999; 21: 679-682
29 Duman R. Depression: a case of neuronal life and death?. Biol Psychiatry 2004; 56: 140-145
30 Malberg JE, Eisch AJ, Nestler EJ et al. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 2000; 20: 9104-9110
31 Deuschle M, Hamann B, Meichel C et al. Antidepressive treatment with amitriptyline and paroxetine: effects on saliva cortisol concentrations. J Clin Psychopharmacol 2003; 23: 201-205
32 Scharnholz B, Weber-Hamann B, Lederbogen F et al. Antidepressant treatment with mirtazapine, but not venlafaxine, lowers cortisol concentrations in saliva: a randomised open trial. Psychiatry Res 2010; 177: 109-113
33 Karege F, Bondolfi G, Gervasoni N et al. Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity. Biol Psychiatry 2005; 57: 1068-1072
34 Karege F, Perret G, Bondolfi G et al. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 2002; 109: 143-148
35 Pan W, Banks WA, Fasold MB et al. Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 1998; 37: 1553-1561
36 Zhang Y, Gu F, Chen J et al. Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat. Brain Res 2010; 1366: 141-148
37 Schins A, Hamulyák K, Scharpé S et al. Whole blood serotonin and platelet activation in depressed post-myocardial infarction patients. Life Sci 2004; 76: 637-650
38 Tharmapathy P, Selheim F, Odegaard K et al. Venlafaxine treatment stimulates blood platelet activity. J Clin Psychopharmacol 2000; 20: 589-590
39 Serra-Millàs M, López-Vílchez I, Navarro V et al. Changes in plasma and platelet BDNF levels induced by S-citalopram in major depression. Psychopharmacology 2011; 216: 1-8
40 Trajkovska V, Marcussen AB, Vinberg M et al. Measurement of brain-derived neurotrophic factor: methodological aspects and demographic data. Brain Res Bull 2007; 73: 143-149
41 Sen S, Nesse RM, Stoltenberg SF et al. A BDNF coding variant is associated with the NEO personality inventory domain neuroticism, a risk factor for depression. Neuropsychopharmacology 2003; 28: 397-401
42 Balu DT, Hoshaw BA, Malberg JE et al. Differential regulation of central BDNF protein levels by antidepressants and non-antidepressant drug treatments. Brain Res 2008; 1211: 37-43