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  • The International Journal of Neuropsychopharmacology, Volume 11, Issue 8
  • December 2008, pp. 1169-1180

A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression

  • André Russowsky Brunoni (a1) (a2), Mariana Lopes (a1) and Felipe Fregni (a1)
  • DOI: http://dx.doi.org/10.1017/S1461145708009309
  • Published online: 28 August 2008
Abstract
Abstract

Several clinical studies on major depressive disorder (MDD) have shown that blood brain-derived neurotrophic factor (BDNF) – a factor used to index neuroplasticity – is associated with depression response; however, the results are mixed. The purpose of our study was to evaluate whether BDNF levels are correlated with improvement of depression. We performed a systematic review and meta-analysis of the literature, searching Medline, Cochrane Central, SciELO databases and reference lists from retrieved articles for clinical studies comparing mean BDNF blood levels in depressed patients pre- and post-antidepressant treatments or comparing depressed patients with healthy controls. Two reviewers independently searched for eligible studies and extracted outcome data using a structured form previously elaborated. Twenty articles, including 1504 subjects, met our inclusion criteria. The results showed that BDNF levels increased significantly after antidepressant treatment (effect size 0.62, 95% CI 0.36–0.88, random effects model). In addition, there was a significant correlation between changes in BDNF level and depression scores changes (p=0.02). Moreover, the results were robust according to the sensitivity analysis and Begg's funnel plot results did not suggest publication bias. Finally, there was a difference between pre-treatment patients and healthy controls (effect size 0.91, 95% CI 0.70–1.11) and a small but significant difference between treated patients and healthy controls (effect size 0.34, 95% CI 0.02–0.66). Our results show that BDNF levels are associated with clinical changes in depression; supporting the notion that depression improvement is associated with neuroplastic changes.

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Corresponding author
Address for correspondence: F. Fregni, M.D., Ph.D., 330 Brookline Ave – KS 452, Boston, MA 02215, USA. Tel.: (617) 667-5272Fax: (617) 975-5322E-mail: ffregni@bidmc.harvard.edu
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SJ Allen , D Dawbarn (2006). Clinical relevance of the neurotrophins and their receptors. Clinical Science (London) 110, 175191.

MN Alme , K Wibrand , G Dagestad , CR Bramham (2007). Chronic fluoxetine treatment induces brain region-specific upregulation of genes associated with BDNF-induced long-term potentiation. Neural Plasticity. Published online: 19 September 2007. doi:10.1155/2007/26496.

C Aydemir , ES Yalcin , S Aksaray , C Kisa , SG Yildirim , T Uzbay , E Goka (2006). Brain-derived neurotrophic factor (BDNF) changes in the serum of depressed women. Progress in Neuropsychopharmacology and Biological Psychiatry 30, 12561260.

O Aydemir , A Deveci , F Taneli (2005). The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study. Progress in Neuropsychopharmacology and Biological Psychiatry 29, 261265.

O Aydemir , A Deveci , OE Taskin , F Taneli , A Esen-Danaci (2007). Serum brain-derived neurotrophic factor level in dysthymia: a comparative study with major depressive disorder. Progress in Neuropsychopharmacology and Biological Psychiatry 31, 10231026.

DT Balu , BA Hoshaw , JE Malberg , S Rosenzweig-Lipson , LE Schechter , I Lucki (2008). Differential regulation of central BDNF protein levels by antidepressant and non-antidepressant drug treatments. Brain Research 1211, 3743.

S Begliuomini , E Casarosa , N Pluchino , E Lenzi , M Centofanti , L Freschi , M Pieri , AD Genazzani , S Luisi , AR Genazzani (2007). Influence of endogenous and exogenous sex hormones on plasma brain-derived neurotrophic factor. Human Reproduction 22, 9951002.

L Bocchio-Chiavetto , R Zanardini , M Bortolomasi , M Abate , M Segala , M Giacopuzzi , MA Riva , E Marchina , P Pasqualetti , J Perez , (2006). Electroconvulsive Therapy (ECT) increases serum Brain Derived Neurotrophic Factor (BDNF) in drug resistant depressed patients. European Neuropsychopharmacology 16, 620624.

CR Bramham , E Messaoudi (2005). BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis. Progress in Neurobiology 76, 99125.

S Campbell , M Marriott , C Nahmias , GM MacQueen (2004). Lower hippocampal volume in patients suffering from depression: a meta-analysis. American Journal of Psychiatry 161, 598607.

A Deveci , O Aydemir , O Taskin , F Taneli , A Esen-Danaci (2007a). Serum BDNF levels in suicide attempters related to psychosocial stressors: a comparative study with depression. Neuropsychobiology 56, 9397.

A Deveci , O Aydemir , O Taskin , F Taneli , A Esen-Danaci (2007b). Serum brain-derived neurotrophic factor levels in conversion disorder: comparative study with depression. Psychiatry and Clinical Neurosciences 61, 571573.

RS Duman , LM Monteggia (2006). A neurotrophic model for stress-related mood disorders. Biological Psychiatry 59, 11161127.

M Egger , GD Smith , AN Phillips (1997). Meta-analysis: principles and procedures. British Medical Journal 315, 15331537.

A Gartner , V Staiger (2002). Neurotrophin secretion from hippocampal neurons evoked by long-term-potentiation-inducing electrical stimulation patterns. Proceedings of the National Academy of Sciences USA 99, 63866391.

N Gervasoni , JM Aubry , G Bondolfi , C Osiek , M Schwald , G Bertschy , F Karege (2005). Partial normalization of serum brain-derived neurotrophic factor in remitted patients after a major depressive episode. Neuropsychobiology 51, 234238.

AS Gonul , F Akdeniz , F Taneli , O Donat , C Eker , S Vahip (2005). Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients. European Archives of Psychiatry and Clinical Neuroscience 255, 381386.

M Gratacos , JR Gonzalez , JM Mercader , R de Cid , M Urretavizcaya , X Estivill (2007). Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biological Psychiatry 61, 911922.

JP Hamilton , M Siemer , IH Gotlib (2008). Amygdala volume in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Molecular Psychiatry. Published online: 27 May 2008. doi:10.1038/mp.2008.57.

AW Henkel , W Sperling , A Rotter , U Reulbach , C Reichardt , D Bonsch , JM Maler , J Kornhuber , J Wiltfang (2008). Antidepressant drugs modulate growth factors in cultured cells. BMC Pharmacology 8, 6.

TL Huang , CT Lee , YL Liu (2008). Serum brain-derived neurotrophic factor levels in patients with major depression: effects of antidepressants. Journal of Psychiatric Research 42, 521525.

F Karege , G Bondolfi , N Gervasoni , M Schwald , JM Aubry , G Bertschy (2005). Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity. Biological Psychiatry 57, 10681072.

F Karege , G Perret , G Bondolfi , M Schwald , G Bertschy , JM Aubry (2002a). Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Research 109, 143148.

F Karege , M Schwald , M Cisse (2002b). Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets. Neuroscience Letters 328, 261264.

G Kempermann , G Kronenberg (2003). Depressed new neurons – adult hippocampal neurogenesis and a cellular plasticity hypothesis of major depression. Biological Psychiatry 54, 499503.

YK Kim , HP Lee , SD Won , EY Park , HY Lee , BH Lee , SW Lee , D Yoon , C Han , DJ Kim , (2007). Low plasma BDNF is associated with suicidal behavior in major depression. Progress in Neuropsychopharmacology and Biological Psychiatry 31, 7885.

G Knapp , J Hartung (2003). Improved tests for a random effects meta-regression with a single covariate. Statistics in Medicine 22, 26932710.

R Koyama , Y Ikegaya (2005). To BDNF or not to BDNF: that is the epileptic hippocampus. Neuroscientist 11, 282287.

SD Kuipers , A Trentani , JA Den Boer , GJ Ter Horst (2003). Molecular correlates of impaired prefrontal plasticity in response to chronic stress. Journal of Neurochemistry 85, 13121323.

UE Lang , M Bajbouj , J Gallinat , R Hellweg (2006). Brain-derived neurotrophic factor serum concentrations in depressive patients during vagus nerve stimulation and repetitive transcranial magnetic stimulation. Psychopharmacology (Berlin) 187, 5659.

BH Lee , H Kim , SH Park , YK Kim (2007). Decreased plasma BDNF level in depressive patients. Journal of Affective Disordrs 101, 239244.

M Lommatzsch , D Zingler , K Schuhbaeck , K Schloetcke , C Zingler , P Schuff-Werner , JC Virchow (2005). The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiology of Aging 26, 115123.

CM Marano , P Phatak , UR Vemulapalli , A Sasan , MR Nalbandyan , S Ramanujam , S Soekadar , M Demosthenous , WT Regenold (2007). Increased plasma concentration of brain-derived neurotrophic factor with electroconvulsive therapy: a pilot study in patients with major depression. Journal of Clinical Psychiatry 68, 512517.

P Monteleone , C Serritella , V Martiadis , M Maj (2008). Decreased levels of serum brain-derived neurotrophic factor in both depressed and euthymic patients with unipolar depression and in euthymic patients with bipolar I and II disorders. Bipolar Disorder 10, 95100.

MJ Muller , H Himmerich , B Kienzle , A Szegedi (2003). Differentiating moderate and severe depression using the Montgomery-Asberg depression rating scale (MADRS). Journal of Affective Disorders 77, 255260.

W Pan , WA Banks , MB Fasold , J Bluth , AJ Kastin (1998). Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 37, 15531561.

A Piccinni , D Marazziti , M Catena , L Domenici , A Del Debbio , C Bianchi , C Mannari , C Martini , E Da Pozzo , E Schiavi , (2008). Plasma and serum brain-derived neurotrophic factor (BDNF) in depressed patients during 1 year of antidepressant treatments. Journal of Affective Disorders 105, 279283.

K Ren , R Dubner (2007). Pain facilitation and activity-dependent plasticity in pain modulatory circuitry: role of BDNF-TrkB signaling and NMDA receptors. Molecular Neurobiology 35, 224235.

HG Ruhe , NS Mason , AH Schene (2007). Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Molecular Psychiatry 12, 331359.

E Shimizu , K Hashimoto , N Okamura , K Koike , N Komatsu , C Kumakiri , M Nakazato , H Watanabe , N Shinoda , S Okada , (2003). Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biological Psychiatry 54, 7075.

V Trajkovska , AB Marcussen , M Vinberg , P Hartvig , S Aznar , GM Knudsen (2007). Measurements of brain-derived neurotrophic factor: methodological aspects and demographical data. Brain Research Bulletin 73, 143149.

R Ventimiglia , PE Mather , BE Jones , RM Lindsay (1995). The neurotrophins BDNF, NT-3 and NT-4/5 promote survival and morphological and biochemical differentiation of striatal neurons in vitro. European Journal of Neuroscience 7, 213222.

P Videbech , B Ravnkilde (2004). Hippocampal volume and depression: a meta-analysis of MRI studies. American Journal of Psychiatry 161, 19571966.

B Winter , C Breitenstein , FC Mooren , K Voelker , M Fobker , A Lechtermann , K Krueger , A Fromme , C Korsukewitz , A Floel , (2007). High impact running improves learning. Neurobiology of Learning and Memory 87, 597609.

D Wu (2005). Neuroprotection in experimental stroke with targeted neurotrophins. NeuroRx 2, 120128.

R Yoshimura , M Mitoma , A Sugita , H Hori , T Okamoto , W Umene , N Ueda , J Nakamura (2007). Effects of paroxetine or milnacipran on serum brain-derived neurotrophic factor in depressed patients. Progress in Neuropsychopharmacology and Biological Psychiatry 31, 10341037.

T Yukimasa , R Yoshimura , A Tamagawa , T Uozumi , K Shinkai , N Ueda , S Tsuji , J Nakamura (2006). High-frequency repetitive transcranial magnetic stimulation improves refractory depression by influencing catecholamine and brain-derived neurotrophic factors. Pharmacopsychiatry 39, 5259.

R Zanardini , A Gazzoli , M Ventriglia , J Perez , S Bignotti , PM Rossini , M Gennarelli , L Bocchio-Chiavetto (2006). Effect of repetitive transcranial magnetic stimulation on serum brain derived neurotrophic factor in drug resistant depressed patients. Journal of Affective Disorders 91, 8386.

AA Ziegenhorn , O Schulte-Herbruggen , H Danker-Hopfe , M Malbranc , HD Hartung , D Anders , UE Lang , E Steinhagen-Thiessen , RT Schaub , R Hellweg (2007). Serum neurotrophins – a study on the time course and influencing factors in a large old age sample. Neurobiology of Aging 28, 14361445.

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