Top

Systematic Reviews

Published in:

Open Access 01-12-2015 | Research

Association between BDNF levels and suicidal behaviour: a systematic review and meta-analysis

Authors: Rebecca B. Eisen, Stefan Perera, Laura Banfield, Rebecca Anglin, Luciano Minuzzi, Zainab Samaan

Published in: Systematic Reviews | Issue 1/2015

Abstract

Background

Suicidal behaviour is a complex phenomenon with a multitude of risk factors. Brain-derived neurotrophic factor (BDNF), a protein crucial to nervous system function, may be involved in suicide risk. The objective of this systematic review is to evaluate and summarize the literature examining the relationship between BDNF levels and suicidal behaviour.

Methods

A predefined search strategy was used to search MEDLINE, EMBASE, PsychINFO, and CINAHL from inception to December 2015. Studies were included if they investigated the association between BDNF levels and suicidal behaviours (including completed suicide, attempted suicide, or suicidal ideation) by comparing BDNF levels in groups with and without suicidal behaviour. Only the following observational studies were included: case-control and cohort studies. Both clinical- and community-based samples were included. Screening, data extraction, and risk of bias assessment were conducted in duplicate.

Results

Six-hundred thirty-one articles were screened, and 14 were included in the review. Three studies that assessed serum BDNF levels in individuals with suicide attempts and controls were combined in a meta-analysis that showed no significant association between serum BDNF and suicide attempts. The remaining 11 studies were not eligible for the meta-analysis and provided inconsistent findings regarding associations between BDNF and suicidal behaviour.

Conclusions

The findings of the meta-analysis indicate that there is no significant association between serum BDNF and attempted suicide. The qualitative review of the literature did not provide consistent support for an association between BDNF levels and suicidal behaviour. The evidence has significant methodological limitations.

Systematic review registration

PROSPERO CRD42015015871

Available only for authorised users

WHO. Preventing suicide: a global imperative. 2014.

Mann JJ. Neurobiology of suicidal behaviour. Nat Rev Neurosci. 2003;4(10):819–28. doi:10.1038/nrn1220.PubMedCrossRef

Crump C, Sundquist K, Sundquist J, Winkleby MA. Sociodemographic, psychiatric and somatic risk factors for suicide: a Swedish national cohort study. Psychol Med. 2014;44(2):279–89. doi:10.1017/S0033291713000810.PubMedCrossRef

Harris EC, Barraclough B. Suicide as an outcome for mental disorders. A meta-analysis. Br J Psychiatry. 1997;170:205–28.PubMedCrossRef

Clayden RC, Zaruk A, Meyre D, Thabane L, Samaan Z. The association of attempted suicide with genetic variants in the SLC6A4 and TPH genes depends on the definition of suicidal behavior: a systematic review and meta-analysis. Transl Psychiatry. 2012;2, e166. doi:10.1038/tp.2012.96.PubMedPubMedCentralCrossRef

Dwivedi Y. Brain-derived neurotrophic factor in suicide pathophysiology. In: Dwivedi Y, editor. The Neurobiological Basis of Suicide. Frontiers in Neuroscience. Boca Raton (FL). 2012.CrossRef

Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677–736. doi:10.1146/annurev.neuro.24.1.677.PubMedPubMedCentralCrossRef

Altshuler LL, Casanova MF, Goldberg TE, Kleinman JE. The hippocampus and parahippocampus in schizophrenic, suicide, and control brains. Arch Gen Psychiatry. 1990;47(11):1029–34.PubMedCrossRef

Rajkowska G. Morphometric methods for studying the prefrontal cortex in suicide victims and psychiatric patients. Ann N Y Acad Sci. 1997;836(1):253–68.PubMedCrossRef

10.

Wagner G, Schultz CC, Koch K, Schachtzabel C, Sauer H, Schlosser RG. Prefrontal cortical thickness in depressed patients with high-risk for suicidal behavior. J Psychiatr Res. 2012;46(11):1449–55. doi:10.1016/j.jpsychires.2012.07.013.PubMedCrossRef

11.

Eastwood SL, Harrison PJ. Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood disorders. A review and a Western blot study of synaptophysin, GAP-43 and the complexins. Brain Res Bull. 2001;55(5):569–78.PubMedCrossRef

12.

Sackeim HA. Functional brain circuits in major depression and remission. Arch Gen Psychiatry. 2001;58(7):649–50.PubMedCrossRef

13.

Garcia R. Stress, synaptic plasticity, and psychopathology. Rev Neurosci. 2002;13(3):195–208.PubMed

14.

Fossati P, Radtchenko A, Boyer P. Neuroplasticity: from MRI to depressive symptoms. Eur Neuropsychopharmacol. 2004;14 Suppl 5:S503–10. doi:10.1016/j.euroneuro.2004.09.001.PubMedCrossRef

15.

Araya AV, Orellana X, Espinoza J. Evaluation of the effect of caloric restriction on serum BDNF in overweight and obese subjects: preliminary evidences. Endocrine. 2008;33(3):300–4.PubMedCrossRef

16.

Seifert T, Brassard P, Wissenberg M, Rasmussen P, Nordby P, Stallknecht B, et al. Endurance training enhances BDNF release from the human brain. Am J Physiol Regul Integr Comp Physiol. 2010;298(2):R372–7. doi:10.1152/ajpregu.00525.2009.PubMedCrossRef

17.

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(7):791–800. doi:10.1038/mp.2013.105.PubMedCrossRef

18.

Bus BA, Molendijk ML, Penninx BJ, Buitelaar JK, Kenis G, Prickaerts J, et al. Determinants of serum brain-derived neurotrophic factor. Psychoneuroendocrinology. 2011;36(2):228–39. doi:10.1016/j.psyneuen.2010.07.013.PubMedCrossRef

19.

Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res. 2002;109(2):143–8.PubMedCrossRef

20.

Terracciano A, Lobina M, Piras MG, Mulas A, Cannas A, Meirelles O, et al. Neuroticism, depressive symptoms, and serum BDNF. Psychosom Med. 2011;73(8):638–42. doi:10.1097/PSY.0b013e3182306a4f.PubMedPubMedCentralCrossRef

21.

Karege F, Bondolfi G, Gervasoni N, Schwald M, Aubry JM, Bertschy G. 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(9):1068–72. doi:10.1016/j.biopsych.2005.01.008.PubMedCrossRef

22.

Paska AV, Zupanc T, Pregelj P. The role of brain-derived neurotrophic factor in the pathophysiology of suicidal behavior. Psychiatr Danub. 2013;25 Suppl 2:S341–4.PubMed

23.

Smith MA, Makino S, Kvetnansky R, Post RM. Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci. 1995;15(3 Pt 1):1768–77.PubMed

24.

Fuchikami M, Morinobu S, Kurata A, Yamamoto S, Yamawaki S. Single immobilization stress differentially alters the expression profile of transcripts of the brain-derived neurotrophic factor (BDNF) gene and histone acetylation at its promoters in the rat hippocampus. Int J Neuropsychopharmacol. 2009;12(1):73–82. doi:10.1017/S1461145708008997.PubMedCrossRef

25.

Rasmusson AM, Shi L, Duman R. Downregulation of BDNF mRNA in the hippocampal dentate gyrus after re-exposure to cues previously associated with footshock. Neuropsychopharmacology. 2002;27(2):133–42. doi:10.1016/S0893-133X(02)00286-5.PubMedCrossRef

26.

Pizarro JM, Lumley LA, Medina W, Robison CL, Chang WE, Alagappan A, et al. Acute social defeat reduces neurotrophin expression in brain cortical and subcortical areas in mice. Brain Res. 2004;1025(1–2):10–20. doi:10.1016/j.brainres.2004.06.085.PubMedCrossRef

27.

Dwivedi Y, Rizavi HS, Conley RR, Roberts RC, Tamminga CA, Pandey GN. Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch Gen Psychiatry. 2003;60(8):804–15. doi:10.1001/archpsyc.60.8.804.PubMedCrossRef

28.

Karege F, Vaudan G, Schwald M, Perroud N, La Harpe R. Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs. Brain Res Mol Brain Res. 2005;136(1–2):29–37. doi:10.1016/j.molbrainres.2004.12.020.PubMedCrossRef

29.

Deveci A, Aydemir O, Taskin O, Taneli F, Esen-Danaci A. Serum BDNF levels in suicide attempters related to psychosocial stressors: a comparative study with depression. Neuropsychobiology. 2007;56(2–3):93–7. doi:10.1159/000111539.PubMedCrossRef

30.

Kim YK, Lee HP, Won SD, Park EY, Lee HY, Lee BH, et al. Low plasma BDNF is associated with suicidal behavior in major depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 2007;31(1):78–85. doi:10.1016/j.pnpbp.2006.06.024.CrossRef

31.

Lee BH, Kim H, Park SH, Kim YK. Decreased plasma BDNF level in depressive patients. J Affect Disord. 2007;101(1–3):239–44. doi:10.1016/j.jad.2006.11.005.PubMedCrossRef

32.

Eisen R, Perera S, Bawor M, Banfield L, Anglin R, Minuzzi L, et al. Association between BDNF levels and suicidal behaviour: a systematic review protocol. Systematic Reviews. 2015;4(1):56. doi:10.1186/s13643-015-0047-x.PubMedPubMedCentralCrossRef

33.

Viera AJ, Garrett JM. Understanding interobserver agreement: the kappa statistic. Fam Med. 2005;37(5):360–3.PubMed

34.

Liang W, Zhang H-M, Zhang H-Y, L-X LV. Association of brain-derived neurotrophic factor in peripheral blood and gene expression to suicidal behaviour in patients with depression. Chin Ment Health J. 2012;26(10):5.

35.

Wells GA, Shea B, O’connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2000.

36.

Higgins JPT, Green S, Cochrane Collaboration. Cochrane handbook for systematic reviews of interventions. Cochrane book series. Chichester, England. Hoboken, NJ: Wiley-Blackwell; 2008.CrossRef

37.

Grah M, Mihanovic M, Ruljancic N, Restek-Petrovic B, Molnar S, Jelavic S. Brain-derived neurotrophic factor as a suicide factor in mental disorders. Acta neuropsychiatrica. 2014:1–8. doi:10.1017/neu.2014.27

38.

Pinheiro RT, Pinheiro KA, da Cunha Coelho FM, de Avila Quevedo L, Gazal M, da Silva RA, et al. Brain-derived neurotrophic factor levels in women with postpartum affective disorder and suicidality. Neurochem Res. 2012;37(10):2229–34. doi:10.1007/s11064-012-0851-9.PubMedCrossRef

39.

Banerjee R, Ghosh AK, Ghosh B, Bhattacharyya S, Mondal AC. Decreased mRNA and protein expression of BDNF, NGF, and their receptors in the hippocampus from suicide: an analysis in human postmortem brain. Clin Med Insights Pathol. 2013;6:1–11. doi:10.4137/CMPath.S12530.PubMedPubMedCentralCrossRef

40.

Maheu ME, Davoli MA, Turecki G, Mechawar N. Amygdalar expression of proteins associated with neuroplasticity in major depression and suicide. J Psychiatr Res. 2013;47(3):384–90. doi:10.1016/j.jpsychires.2012.11.013.PubMedCrossRef

41.

Martinez JM, Garakani A, Yehuda R, Gorman JM. Proinflammatory and “resiliency” proteins in the CSF of patients with major depression. Depress Anxiety. 2012;29(1):32–8. doi:10.1002/da.20876.PubMedCrossRef

42.

Park YM, Lee BH, Um TH, Kim S. Serum BDNF levels in relation to illness severity, suicide attempts, and central serotonin activity in patients with major depressive disorder: a pilot study. PLoS One. 2014;9(3), e91061. doi:10.1371/journal.pone.0091061.PubMedPubMedCentralCrossRef

43.

Huang TL, Lee CT. Associations between serum brain-derived neurotrophic factor levels and clinical phenotypes in schizophrenia patients. J Psychiatr Res. 2006;40(7):664–8. doi:10.1016/j.jpsychires.2005.11.004.PubMedCrossRef

44.

Cohen J. Statistical power analysis for the behavioral sciences. 1977. rev. Lawrence Erlbaum Associates, Inc.

45.

Lee BH, Kim YK. Reduced platelet BDNF level in patients with major depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 2009;33(5):849–53. doi:10.1016/j.pnpbp.2009.04.002.CrossRef

46.

Lewis DA. The human brain revisited: opportunities and challenges in postmortem studies of psychiatric disorders. Neuropsychopharmacology. 2002;26(2):143–54. doi:10.1016/S0893-133X(01)00393-1.PubMedCrossRef

47.

Dwivedi Y, Rizavi HS, Pandey GN. Antidepressants reverse corticosterone-mediated decrease in brain-derived neurotrophic factor expression: differential regulation of specific exons by antidepressants and corticosterone. Neuroscience. 2006;139(3):1017–29. doi:10.1016/j.neuroscience.2005.12.058.PubMedPubMedCentralCrossRef

48.

Golden E, Emiliano A, Maudsley S, Windham BG, Carlson OD, Egan JM, et al. Circulating brain-derived neurotrophic factor and indices of metabolic and cardiovascular health: data from the Baltimore Longitudinal Study of Aging. PLoS One. 2010;5(4), e10099. doi:10.1371/journal.pone.0010099.PubMedPubMedCentralCrossRef

Title: Association between BDNF levels and suicidal behaviour: a systematic review and meta-analysis
Authors: Rebecca B. Eisen
Stefan Perera
Laura Banfield
Rebecca Anglin
Luciano Minuzzi
Zainab Samaan
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Systematic Reviews / Issue 1/2015
Electronic ISSN: 2046-4053
DOI: https://doi.org/10.1186/s13643-015-0179-z

At a glance: The STEP trials

Springer Medicine

Association between BDNF levels and suicidal behaviour: a systematic review and meta-analysis

Abstract

Background

Methods

Results

Conclusions

Systematic review registration

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Systematic review registration

Please log in to get access to this content

Other articles of this Issue 1/2015

Role of preoperative intravenous iron therapy to correct anemia before major surgery: study protocol for systematic review and meta-analysis

The risk of intra-cranial haemorrhage in those presenting late to the ED following a head injury: a systematic review

Involving people with diabetes and the wider community in diabetes research: a realist review protocol

Assessing cost-effectiveness of HPV vaccines with decision analytic models: what are the distinct challenges of low- and middle-income countries? A protocol for a systematic review

Prognostic factors for tumor recurrence in patients with clinical stage I seminoma undergoing surveillance—protocol for a systematic review

A systematic review investigating the cumulative incidence of chronic kidney disease in young adults with impaired glucose tolerance