High baseline BDNF serum levels and early psychopathological improvement are predictive of treatment outcome in major depression
- 525 Downloads
Major depressive disorder has been associated with low serum levels of brain-derived neurotrophic factor (sBDNF), which is functionally involved in neuroplasticity. Although sBDNF levels tend to normalize following psychopathological improvement with antidepressant treatment, it is unclear how closely sBDNF changes are associated with treatment outcome.
To examine whether baseline sBDNF or early changes in sBDNF are predictive of response to therapy.
Twenty-five patients with major depressive disorder underwent standardized treatment with duloxetine. Severity of depression, measured by the Hamilton Depression Rating Scale, and sBDNF were assessed at baseline, and after 1, 2, and 6 weeks of treatment. Therapy outcome after 6 weeks was defined as response (≥50 % reduction in baseline Hamilton Depression Rating score) and remission (Hamilton Depression Rating score <8). The predictive values for treatment outcome of baseline sBDNF, and early (i.e., ≤2 weeks) changes in sBDNF and Hamilton Depression Rating score were also assessed.
At baseline, sBDNF correlated with Hamilton Depression Rating scores. Treatment response was associated with a higher baseline sBDNF concentration, and a greater Hamilton Depression Rating score reduction after 1 and 2 weeks. A greater early rise in sBDNF correlated with a decreased early Hamilton Depression Rating score reduction.
Even though higher baseline sBDNF levels are associated with more severe depression, they may reflect an increased capacity to respond to treatment. In contrast, changes in sBDNF over the full course of treatment are not associated with psychopathological improvement.
KeywordsBrain-derived neurotrophic factor (BDNF) Serum Depression Treatment outcome Early response Response Remission Antidepressants Serotonin norepinephrine reuptake inhibitor (SNRI) Duloxetine
This study is an Investigator Initiated Study (ITT) financed by a special grant from Eli Lilly SA, Switzerland. The company had, however, no influence on either the designing or writing of the protocol of the study or analysis and interpretation of study results. The preparation of the manuscript for publication was not supported by the company. E. H. and A. D. are members of the Eli Lilly Advisory Board. A. D. has consulted for the company on various occasions and was involved in the preparation of paid expert reports and educational programs for GPs. No potential conflicts of interests exist for other authors. The authors thank Nick Emler (Surrey, UK) for proofreading the manuscript.
- Bocchio-Chiavetto L, Bagnardi V, Zanardini R, Molteni R, Nielsen MG, Placentino A, Giovannini C, Rillosi L, Ventriglia M, Riva MA, Gennarelli M (2010) Serum and plasma BDNF levels in major depression: a replication study and meta-analyses. World J Biol Psychiatry 11:763–773PubMedCrossRefGoogle Scholar
- Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT (2001) Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology 25:871–880PubMedCrossRefGoogle Scholar
- Cohen J (1988) Statistical power analysis for the behavioral sciences. Lawrence Erlbaum Associates, HillsdaleGoogle Scholar
- De Foubert G, Carney SL, Robinson CS, Destexhe EJ, Tomlinson R, Hicks CA, Murray TK, Gaillard JP, Deville C, Xhenseval V, Thomas CE, O'Neill MJ, Zetterström TS (2004) Fluoxetine-induced change in rat brain expression of brain-derived neurotrophic factor varies depending on length of treatment. Neuroscience 128:597–604PubMedCrossRefGoogle Scholar
- Dreimüller N, Schlicht KF, Wagner S, Peetz D, Borysenko L, Hiemke C, Lieb K, Tadić A (2012) Early reactions of brain-derived neurotrophic factor in plasma (pBDNF) and outcome to acute antidepressant treatment in patients with major depression. Neuropharmacology 62:264–269PubMedCrossRefGoogle Scholar
- Kocabas NA, Antonijevic I, Faghel C, Forray C, Kasper S, Lecrubier Y, Linotte S, Massat I, Mendlewicz J, Noro M, Montgomery S, Oswald P, Snyder L, Zohar J, Souery D (2011) Brain-derived neurotrophic factor gene polymorphisms: influence on treatment response phenotypes of major depressive disorder. Int Clin Psychopharmacol 26:1–10PubMedCrossRefGoogle Scholar
- Larsen MH, Rosenbrock H, Sams-Dodd F, Mikkelsen JD (2007) Expression of brain derived neurotrophic factor, activity-regulated cytoskeleton protein mRNA, and enhancement of adult hippocampal neurogenesis in rats after sub-chronic and chronic treatment with the triple monoamine re-uptake inhibitor tesofensine. Eur J Pharmacol 555:115–121PubMedCrossRefGoogle Scholar
- Matrisciano F, Bonaccorso S, Ricciardi A, Scaccianoce S, Panaccione I, Wang L, Ruberto A, Tatarelli R, Nicoletti F, Girardi P, Shelton RC (2009) Changes in BDNF serum levels in patients with major depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine. J Psychiatr Res 43:247–254Google Scholar
- Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, Nakazato M, Watanabe H, Shinoda N, Okada S, Iyo M (2003) Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 54:70–75PubMedCrossRefGoogle Scholar
- Tadić A, Wagner S, Schlicht KF, Peetz D, Borysenko L, Dreimüller N, Hiemke C, Lieb K (2011) The early non-increase of serum BDNF predicts failure of antidepressant treatment in patients with major depression: a pilot study. Prog Neuropsychopharmacol Biol Psychiatry 35:415–420PubMedCrossRefGoogle Scholar
- Watanabe K, Hashimoto E, Ukai W, Ishii T, Yoshinaga T, Ono T, Tateno M, Watanabe I, Shirasaka T, Saito S, Saito T (2010) Effect of antidepressants on brain-derived neurotrophic factor (BDNF) release from platelets in the rats. Prog Neuropsychopharmacol Biol Psychiatry 34:1450–1454PubMedCrossRefGoogle Scholar
- World Health Organization (1994) ICD-10 classification of mental and behavioural disorders with glossary and diagnostic criteria for research ICD10:DCR-10. Churchill Livingstone, EdinburghGoogle Scholar
- Ziegenhorn AA, Schulte-Herbrüggen O, Danker-Hopfe H, Malbranc M, Hartung HD, Anders D, Lang UE, Steinhagen-Thiessen E, Schaub RT, Hellweg R (2007) Serum neurotrophins—a study on the time course and influencing factors in a large old age sample. Neurobiol Aging 28:1436–1445PubMedCrossRefGoogle Scholar