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No effect of escitalopram versus placebo on brain-derived neurotrophic factor in healthy individuals: a randomised trial

Published online by Cambridge University Press:  17 November 2015

Ulla Knorr ,
Pernille Koefoed ,
Mia H. Greisen Soendergaard ,
Maj Vinberg ,
Ulrik Gether ,
Christian Gluud ,
Jørn Wetterslev ,
Per Winkel  and
Lars V. Kessing
Ulla Knorr*
Affiliation:
Psychiatric Centre Copenhagen, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Pernille Koefoed
Affiliation:
Psychiatric Centre Copenhagen, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Neuropsychiatric Laboratory, Department of Neuroscience and Pharmacology, Psychiatric Centre Copenhagen, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Mia H. Greisen Soendergaard
Affiliation:
Neuropsychiatric Laboratory, Department of Neuroscience and Pharmacology, Psychiatric Centre Copenhagen, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Maj Vinberg
Affiliation:
Psychiatric Centre Copenhagen, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Ulrik Gether
Affiliation:
Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Christian Gluud
Affiliation:
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Jørn Wetterslev
Affiliation:
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Per Winkel
Affiliation:
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Lars V. Kessing
Affiliation:
Psychiatric Centre Copenhagen, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
*
Ulla Knorr, Psychiatric Centre Copenhagen, Rigshospitalet, section 6233, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. Tel: +45 3864 7098; Fax: +45 3864 7077; E-mail: [email protected]
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Abstract

Objective

Brain-derived neurotrophic factor (BDNF) seems to play an important role in the course of depression including the response to antidepressants in patients with depression. We aimed to study the effect of an antidepressant intervention on peripheral BDNF in healthy individuals with a family history of depression.

Methods

We measured changes in BDNF messenger RNA (mRNA) expression and whole-blood BDNF levels in 80 healthy first-degree relatives of patients with depression randomly allocated to receive daily tablets of escitalopram 10 mg versus placebo for 4 weeks.

Results

We found no statistically significant difference between the escitalopram and the placebo group in the change in BDNF mRNA expression and whole-blood BDNF levels. Post hoc analyses showed a statistically significant negative correlation between plasma escitalopram concentration and change in whole-blood BDNF levels in the escitalopram-treated group.

Conclusion

The results of this randomised trial suggest that escitalopram 10 mg has no effect on peripheral BDNF levels in healthy individuals.

Keywords

affective disordersbrain-derived neurotrophic factor (BDNF)escitalopramhealthytrial
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 28 , Issue 2 , April 2016 , pp. 101 - 109
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Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

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References

1. Duman, RS, Heninger, GR, Nestler, EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry 1997;54:597–606.CrossRefGoogle ScholarPubMed
2. Cai, S, Huang, S, Hao, W. New hypothesis and treatment targets of depression: an integrated view of key findings. Neurosci Bull 2015;3:161–174.Google Scholar
3. Mossner, R, Mikova, O, Koutsilieri, E et al. Consensus paper of the WFSBP Task Force on Biological Markers: biological markers in depression. World J Biol Psychiatry 2007;8:141–174.CrossRefGoogle ScholarPubMed
4. Frazier, TW, Youngstrom, EA, Frankel, BA et al. Candidate gene associations with mood disorder, cognitive vulnerability, and fronto-limbic volumes. Brain Behav 2014;4:418–430.CrossRefGoogle ScholarPubMed
5. Martinez-Levy, GA, Cruz-Fuentes, CS. Genetic and epigenetic regulation of the brain-derived neurotrophic factor in the central nervous system. Yale J Biol Med 2014;87:173–186.Google ScholarPubMed
6. Schmidt, HD, Duman, RS. Peripheral BDNF produces antidepressant-like effects in cellular and behavioral models. Neuropsychopharmacology 2010;35:2378–2391.Google Scholar
7. Tongiorgi, E. Activity-dependent expression of brain-derived neurotrophic factor in dendrites: facts and open questions. Neurosci Res 2008;61:335–346.Google Scholar
8. Molendijk, ML, Spinhoven, P, Polak, M, Bus, BA, Penninx, BW, Elzinga, BM. Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484). Mol Psychiatry 2014;19:791–800.CrossRefGoogle ScholarPubMed
9. Yoshida, T, Ishikawa, M, Niitsu, T et al. Decreased serum levels of mature brain-derived neurotrophic factor (BDNF), but not its precursor proBDNF, in patients with major depressive disorder. PLoS One 2012;7:e42676.CrossRefGoogle Scholar
10. Zhou, L, Xiong, J, Lim, Y et al. Upregulation of blood proBDNF and its receptors in major depression. J Affect Disord 2013;150:776–784.CrossRefGoogle ScholarPubMed
11. Molendijk, ML, Bus, BA, 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.Google Scholar
12. Hasselbalch, BJ, Knorr, U, Bennike, B, Hasselbalch, SG, Sondergaard, MH, Kessing, LV. Decreased levels of brain-derived neurotrophic factor in the remitted state of unipolar depressive disorder. Acta Psychiatr Scand 2012;126:157–164.Google Scholar
13. Duclot, F, Kabbaj, M. Epigenetic mechanisms underlying the role of brain-derived neurotrophic factor in depression and response to antidepressants. J Exp Biol 2015;218(Pt 1):21–31.CrossRefGoogle ScholarPubMed
14. Polyakova, M, Stuke, K, Schuemberg, K, Mueller, K, Schoenknecht, P, Schroeter, ML. BDNF as a biomarker for successful treatment of mood disorders: a systematic & quantitative meta-analysis. J Affect Disord 2014;174C:432–440.Google Scholar
15. Morilak, DA, Frazer, A. Antidepressants and brain monoaminergic systems: a dimensional approach to understanding their behavioural effects in depression and anxiety disorders. Int J Neuropsychopharmacol 2004;7:193–218.Google Scholar
16. Yoshimura, R, Kishi, T, Hori, H et al. Serum proBDNF/BDNF and response to fluvoxamine in drug-naive first-episode major depressive disorder patients. Ann Gen Psychiatry 2014;13:19.Google Scholar
17. Cattaneo, A, Gennarelli, M, Uher, R et al. Candidate genes expression profile associated with antidepressants response in the GENDEP study: differentiating between baseline ‘predictors’ and longitudinal ‘targets’. Neuropsychopharmacology 2012;38:377–385.CrossRefGoogle ScholarPubMed
18. Hasler, G, Drevets, WC, Gould, TD, Gottesman, II, Manji, HK. Toward constructing an endophenotype strategy for bipolar disorders. Biol Psychiatry 2006;60:93–105.Google Scholar
19. Knorr, U, Vinberg, M, Klose, M et al. Rationale and design of the participant, investigator, observer, and data-analyst-blinded randomized AGENDA trial on associations between gene-polymorphisms, endophenotypes for depression and antidepressive intervention: the effect of escitalopram versus placebo on the combined dexamethasone-corticotrophine releasing hormone test and other potential endophenotypes in healthy first-degree relatives of persons with depression. Trials 2009;10:66.Google Scholar
20. Knorr, U, Vinberg, M, Hansen, A et al. Escitalopram and neuroendocrine response in healthy first-degree relatives to depressed patients – a randomized placebo-controlled trial. PLoS One 2011;6:e2124.Google Scholar
21. Bock, C, Bukh, JD, Vinberg, M, Gether, U, Kessing, LV. Validity of the diagnosis of a single depressive episode in a case register. Clin Pract Epidemiol Ment Health 2009;5:4.CrossRefGoogle Scholar
22. Wing, JK, Babor, T, Brugha, T et al. SCAN. Schedules for Clinical Assessment in Neuropsychiatry. Arch Gen Psychiatry 1990;47:589–593.Google Scholar
23. Bech, P, Kastrup, M, Rafaelsen, OJ. Mini-compendium of rating scales for states of anxiety depression mania schizophrenia with corresponding DSM-III syndromes. Acta Psychiatr Scand Suppl 1986;326:1–37.Google ScholarPubMed
24. Kendler, KS, Kessler, RC, Walters, EE et al. Stressful life events, genetic liability, and onset of an episode of major depression in women. Am J Psychiatry 1995;152:833–842.Google Scholar
25. Trajkovska, V, Vinberg, M, Aznar, S, Knudsen, GM, Kessing, LV. Whole blood BDNF levels in healthy twins discordant for affective disorder: association to life events and neuroticism. J Affect Disord 2008;108:165–169.Google Scholar
26. Trajkovska, V, Marcussen, AB, Vinberg, M, Hartvig, P, Aznar, S, Knudsen, GM. Measurements of brain-derived neurotrophic factor: methodological aspects and demographical data. Brain Res Bull 2007;73:143–149.CrossRefGoogle ScholarPubMed
27. Holm, S. A simple sequentially rejective multiple test procedure. Scand J Stat 1979;6:65–70.Google Scholar
28. Yasui-Furukori, N, Tsuchimine, S, Nakagami, T et al. Association between plasma paroxetine concentration and changes in plasma brain-derived neurotrophic factor levels in patients with major depressive disorder. Hum Psychopharmacol 2011;26:194–200.Google Scholar
29. Modell, S, Lauer, CJ, Schreiber, W, Huber, J, Krieg, JC, Holsboer, F. Hormonal response pattern in the combined DEX-CRH test is stable over time in subjects at high familial risk for affective disorders. Neuropsychopharmacology 1998;18:253–262.Google Scholar
30. Knorr, U, Vinberg, M, Kessing, LV, Wetterslev, J. Salivary cortisol in depressed patients versus control persons: a systematic review and meta-analysis. Psychoneuroendocrinology 2010;35:1275–1286.Google Scholar
31. Haastrup, E, Knorr, U, Erikstrup, C, Kessing, LV, Ullum, H. No evidence for an anti-inflammatory effect of escitalopram intervention in healthy individuals with a family history of depression. J Neuroimmunol 2012;243:69–72.Google Scholar
32. Jing, L, Bu, M. Role of macrophage migration inhibitory factor in glucocorticoid release and glucocorticoid receptor function in rats. Ann Clin Lab Sci 2011;41:14–19.Google Scholar
33. Turner, EH, Matthews, AM, Linardatos, E, Tell, RA, Rosenthal, R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med 2008;358:252–260.CrossRefGoogle ScholarPubMed
34. Sodersten, K, Palsson, E, Ishima, T et al. Abnormality in serum levels of mature brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in mood-stabilized patients with bipolar disorder: a study of two independent cohorts. J Affect Disord 2014;160:1–9.CrossRefGoogle ScholarPubMed