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Brain-derived neurotrophic factor as a suicide factor in mental disorders

Published online by Cambridge University Press:  13 October 2013

Majda Grah*
Affiliation:
Psychiatric Hospital ‘Sveti Ivan’, Department for the Treatment of Psychosis and Borderline States, Jankomir, Zagreb, Croatia
Mate Mihanovic
Affiliation:
Psychiatric Hospital ‘Sveti Ivan’, Jankomir, Zagreb, Croatia
Nedjeljka Ruljancic
Affiliation:
Psychiatric Hospital ‘Sveti Ivan’, Department of Laboratory Diagnostics, Jankomir, Zagreb, Croatia
Branka Restek-Petrovic
Affiliation:
Psychiatric Hospital ‘Sveti Ivan’, Department for Psychotherapeutic Treatment of Neuroses, Psychoses, and Borderline States and Day Hospital, Jankomir, Zagreb, Croatia
Sven Molnar
Affiliation:
Psychiatric Hospital ‘Sveti Ivan’, Department of Neurosis and PTSD, Jankomir, Zagreb, Croatia
Silvana Jelavic
Affiliation:
Psychiatric Hospital ‘Sveti Ivan’, Department of Psychosis, Jankomir, Zagreb, Croatia
*
Majda Grah, Psychiatric Hospital ‘Sveti Ivan’, Jankomir, Zagreb, Croatia.Tel: 0038513430018; Fax: 00385 1 3794116; E-mail: [email protected]

Abstract

Objective

Brain-derived neurotrophic factor (BDNF) plays a critical role in brain plasticity processes and serum levels have been demonstrated to be altered in patients with different mental disorder including suicidal behaviour. The objective of this study was to examine the association between serum BDNF levels as a possible peripheral indicator of suicide behaviour in subjects suffering from depression, personality disorders (PDs) and adjustment disorders (ADs) with or without suicide attempt.

Methods

The research included 172 randomly selected individuals suffering from recurrent depressive disorder (RDD; F 33.2), emotionally unstable PD (F 60.3) and AD (F 43.2), with or without attempted suicide according to the criteria of the ICD-10 (International Statistical Classification of Diseases and Related Health Problems 10th Revision) and 60 phenotypically health control subjects. In the group of patients, 73% subjects took some form of psychopharmacotherapy. Serum BDNF levels were measured by enzyme linked immunosorbent assay.

Results

Subjects with PD and AD with suicide attempts had significantly lower serum BDNF levels than those without suicide attempts. In groups of subjects with PD and AD, those taking psychopharmacotherapy had higher serum BDNF levels. In the group of subjects with RDD, there were no differences with respect to suicide attempts or psychopharmacotherapy. Logistical regression analysis was indicated that psychopharmcotherapy and serum BDNF levels statistically correlated with suicide attempts.

Conclusion

The lower levels of BDNF in subjects suffering from PD and AD with suicide attempts, suggest that the serum BDNF level is a potential marker of suicidal behaviour, independent of mental disorders.

Type
Original Articles
Copyright
© Scandinavian College of Neuropsychopharmacology 2014 

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References

1.Benraiss, A, Chmielnicki, E, Lerner, K, Roh, D, Goldman, SA. Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain. J Neurosci 2001;21:67186731.Google Scholar
2.Huang, TL, Lee, Ct, Liu, YL. Serum brain-derived neurotrophic factor levels in patients with major depression: effects of antidepressants. J Psychiatr Res 2007;42:521527.Google Scholar
3.Lu, B, Je, HS. Neurotrophic regulation of the development and function of the neuromuscular synapses. J Neurocytol 2003;32:931941.Google Scholar
4.Mcallister, AK, Katz, LC, Lo, DC. Neurotrophins and synaptic plasticity. Ann Rev Neurosci 1999;22:295318.Google Scholar
5.Pencea, V, Bingaman, KD, Wiegand, SJ, Luskin, MB. Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus. J Neurosci 2001;21:67066717.CrossRefGoogle ScholarPubMed
6.Poo, MM. Neurotrophins as synaptic regulators. Nat Rev Neurosci 2001;2:2432.Google Scholar
7.Zigova, T, Pencea, V, Wiegand, SJ, Luskin, MB. Intraventricular administration of BDNF increases the number of newly generated neurons in the adult olfactory bulb. Mol Cell Neurosci 1998;11:234245.Google Scholar
8.Dwivedi, Y. Brain-derived neurotrophic factor: role in depression and suicide. Neuropsychiatr Dis Treat 2009;5:433449.Google Scholar
9.Ciammola, A, Sassone, J, Cannella, Met al.Low brain-derived neurotrophic factor (BDNF) levels in serum of Huntington’s disease patients. Am J Med Genet B Neuropsychiatr Genet 2007;144:574577.Google Scholar
10.Hashimoto, K, Iwata, Y, Nakamura, Ket al.Reduced serum levels of brain-derived neurotrophic factor in adult male patients with autism. Prog Neuropsychopharmacol Biol Psychiatry 2006;30:15291531.Google Scholar
11.Ikeda, Y, Yahata, N, Ito, Iet al.Low serum levels of brain-derived neurotrophic factor and epidermal growth factor in patients with chronic schizophrenia. Schizophr Res 2008;101:5866.Google Scholar
12.Machado-Vieira, R, Dietrich, MO, Leke, Ret al.Decreased plasma brain derived neurotrophic factor levels in unmedical bipolar patients during manic episode. Biol Psychiatry 2007;61:142144.Google Scholar
13.Mück-Seler, D, Jakovljevic, M, Pivac, N. Platelet 5-HT concentrations and suicidal behavior in recurrent major depression. J Affect Dis 1996;39:7380.Google Scholar
14.Nakazato, M, Hashimoto, K, Shimizu, Eet al.Decreased levels of serum brain-derived neurotrophic factor in female patients with eating disorders. Biol Psychiatry 2003;54:485490.Google Scholar
15.Nedic, G, Perkovic, MN, Sviglin, KN, Muck-Seler, D, Borovecki, F, Pivac, N. Brain-derived neurotrophic factor Val66Met polymorphism and alcohol-related phenotypes. Prog Neuropsychopharmacol Biol Psychiatry 2013;40:193198.Google Scholar
16.Pivac, N, Kozaric-Kovacic, D, Grubisic-Ilic, Met al.The association between brain-derived neurotrophic factor Val66Met variants and psychotic symptoms in posttraumatic stress disorder. World J Biol Psychiatry 2012;13:306311.CrossRefGoogle ScholarPubMed
17.Spalletta, G, Morris, DW, Angelucci, Fet al.BDNF Val66Met polymorphism is associated with aggressive behavior in schizophrenia. Eur Psychiatry 2010;25:311313.Google Scholar
18.Yasutake, C, Kuroda, K, Yanagawa, T, Okamura, T, Yoneda, H. Serum BDNF, TNF-alpha and IL-1beta levels in dementia patients: comparison between Alzheimer’s disease and vascular dementia. Eur Arch Psychiatry Clin Neurosci 2006;256:402406.Google Scholar
19.Van De Kerkof, NWA, Fekkes, D, Van Der Heijden, FMMA, Verhoeven, WMA. BDNF and S100B in psychotic disoredrs: evidence for an association with treatment responsiveness. Acta Neuropsychiatrica 29:223229.CrossRefGoogle Scholar
20.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;109:143148.CrossRefGoogle ScholarPubMed
21.Shimizu, E, Hashimoto, K, Okamura, Net al.Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 2003;54:7075.Google Scholar
22.Gervasoni, N, Aubry, JM, Bondolfi, Get al.Partial normalisation of serum brain-derived neurotrophic factor in remitted patients after a major depressive episode. Neuropsychobiology 2005;51:234238.Google Scholar
23.Piccinni, A, Marazziti, D, Catena, Met al.Plasma and serum brain-derived neurotrophic factor (BDNF) in depressed patients during 1 year of antidepressant treatments. J Affect Disord 2008;105:279283.CrossRefGoogle ScholarPubMed
24.Aydemir, O, Yalcin, ES, Aksaray, Set al.Brain-derived neurotrophic factor (BDNF) changes in the serum of depressed women. Prog Neuro Psychopharmacol Biol Psychiatry 2006;30:12561260.Google Scholar
25.Yoshimura, R, Mitoma, M, Sugita, Aet al.Effects of paroxetine or milnacipran on serum brain-derived neurotrophic factor in depressed patients. Prog Neuro Psychopharmacol Biol Psychiatry 2007;31:10341037.Google Scholar
26.Monteleone, P, Serritella, C, Martiadis, V, Maj, M. 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 Disord 2008;10:95100.Google Scholar
27.Castrén, E, Rantamäki, T. Role of brain-derived neurotrophic factor in the aetiology of depression: implications for pharmacological treatment. CNS Drugs 2010;24:17.Google Scholar
28.Dreimüller, N, Schlicht, KF, Wagner, Set al.Early reactions of brain-derived neurotrophic factor in plasma (pBDNF) and outcome to acute antidepressant treatment in patients with major depression. Neuropharmacology 2012;62:264269.Google Scholar
29.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;139:10171029.Google Scholar
30.Huang, EJ, Reichardt, LF. Neurotrophins: roles in neuronal development and function. Ann Rev Neurosci 2001;24:677736.Google Scholar
31.Molendijk, ML, Bus, BA, Spinhoven, Pet al.Serum levels of brain-derived neurotrophic factor in major depressive disorder: state-trait issues, clinical features and pharmacological treatment. Mol Psychiatry 2011;16:10881095.Google Scholar
32.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 2013;19:791800.Google Scholar
33.Satomura, E, Baba, H, Nakano, Y, Maeshima, H, Suzuki, T, Arai, H. Correlations between brain-derived neurotrophic factor and clinical symptoms in medicated patients with major depression. J Affect Disord 2011;135:332335.CrossRefGoogle ScholarPubMed
34.Sen, S, Duman, R, Sanacora, G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry 2008;64:527532.Google Scholar
35.Serra-Millas, M, Lopez-Vilchez, I, Navarro, Vet al.Changes in plasma and platelet BDNF levels induced by S-citalopram in major depression. Psychopharmacology 2011;216:18.Google Scholar
36.Dwivedi, Y, Rizavi, HS, Conley, RR, Roberts, RC, Tamminga, CA, Pandey, GM. Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in post-mortem brain of suicide subjects. Arch Gen Psychiatry 2003;60:804815.Google Scholar
37.Karege, F, Vaudan, G, Schwald, M, Perroud, N, La Harpe, R. Neurotrophin levels in post-mortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs. Brain Res Mol Brain Res 2005;136:2937.Google Scholar
38.Kim, YK, Lee, HP, Won, SDet al.Low plasma BDNF is associated with suicidal behavior in major depression. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:7885.Google Scholar
39.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;56:9397.Google Scholar
40.Lee, BH, Kim, YK. BDNF mRNA expression of peripheral blood mononuclear cells was decreased in depressive patients who had or had not recently attempted suicide. J Affect Disord 2010;125:369373.Google Scholar
41.Lee, BH, Kim, H, Park, SH, Kim, YK. Decreased plasma BDNF level in depressive patients. J Affect Disord 2007;101:239244.CrossRefGoogle ScholarPubMed
42.Schenkel, LC, Segal, J, Becker, JA, Manfro, GG, Bianchin, MM, Leistner-Segal, S. The BDNF Val66Met polymorphism is an independent risk factor for high lethality in suicide attempts of depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:940944.Google Scholar
43.Smith, MA, Makino, S, Kvetnansky, R, Post, R. Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 1995;15:17681777.Google Scholar
44.Rassmuson, 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;27:133142.Google Scholar
45.Savitz, J, Van Der Merwe, L, Stein, DJ, Solms, M, Ramesar, RGenotype and childhood sexual trauma moderate neurocognitive performance: a possible role for brain-derived neurotrophic factor and apolipoprotein E variants. Biol Psychiatry 2007;62:391399.Google Scholar
46.WHO. International Statistical Classification of Diseases and Related Health Problems 10th Revision, 2nd edn.Geneva: WHO, 2004.Google Scholar
47.Sheehan, DV, Lecruiber, Y, Sheehan, KHet al.The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59:2233.Google Scholar
48.Shvartzman, P, Weiner, Z, Vardy, D, Friger, M, Sherf, M, Biderman, A. Health services utilization by depressive patients identified by the MINI questionnaire in a primary care setting. Scand J Prim Health Care 2005;23:1825.Google Scholar
49.Garlow, SS, Purselle, D, D'orio, B. Psychiatric emergencies. In: Schatzberg AF, Nemeroff CB, editors. The American Psychiatric Publishing Textbook of Psychopharmacology, 4th edn.Arlington: Psychiatric Publishing, 2009. p. 213240.Google Scholar
50.Schatzberg, AF, Nemeroff, CB. Essentials of clinical psychopharmacology, 3rd edn.Washington: American Psychiatric Publishing, 2013.Google Scholar
51.Taylor, R, Paton, C, Kapur, S. The Maudsley prescribing guidelines in psychiatry, 11th edn. Chichester: Wiley-Blackwell, 2012.Google Scholar
52.Hashimoto, K. Brain-derived neurotrophic factor as a biomarker for mood disorders: an historical overview and future directions. Psychiatry Clin Neurosci 2010;64:341345.Google Scholar
53.Jevtovic, S, Karlovic, D, Mihaljevic-Peles, A, Seric, V, Vrkic, N, Jaksic, N. Serum brain-derived neurotrophic factor (BDNF): the severity and symptomatic dimensions of depression. Psychiatr Danub 2011;23:363369.Google Scholar
54.Zhang, X, Wang, X, Sha, W, Zhou, H, Zhang, Y. Val66Met polymorphism and serum brain-derived neurotrophic factor concentration in depressed patients. Acta Neuropsychiatrica 2011;23:229234.CrossRefGoogle ScholarPubMed
55.Ninan, PT, Shelton, RC, Bao, W, Guico-Pabia, CJ. BDNF, interleukin-6, and salivary cortisol levels in depressed patients treated with desvenlafaxine. Prog Neuropsychopharmacol Biol Psychiatry 2013;48:8691.Google Scholar
56.Dwivedi, Y. Brain-derived neurotrophic factor and suicide pathogenesis. Ann Med 2010;42:8796.Google Scholar
57.Dwivedi, Y, Rizavi, H, Zhang, Het al.Neurotrophin receptor activation and expression in human postmortem brain: effect of suicide. Biol Psychiatry 2009;65:319328.CrossRefGoogle ScholarPubMed