Skip to main content Accessibility help
×
Home

Increased serum brain-derived neurotrophic factor levels following electroconvulsive therapy or antipsychotic treatment in patients with schizophrenia

  • J. Li (a1) (a2) (a3), F. Ye (a2), W. Xiao (a2), X. Tang (a2), W. Sha (a2), X. Zhang (a2) and J. Wang (a1) (a3)...

Abstract

Background

Many schizophrenia patients experience residual symptoms even after treatment. Electroconvulsive therapy (ECT) is often used in medication-resistant schizophrenia patients when pharmacologic interventions have failed; however, the mechanism of action is unclear. Brain-derived neurotrophic factor (BDNF) levels are reduced in drug-naive, first-episode schizophrenia and are increased by antipsychotic treatment. We tested the hypothesis that ECT increases serum BDNF levels by measuring BDNF concentrations in schizophrenia patients before and after they received ECT.

Methods

A total of 160 patients with schizophrenia were examined. The ECT group (n = 80) was treated with antipsychotics and ECT (eight to 10 sessions administered every other day). The drug therapy group (n = 80) received only antipsychotic treatment. A control group (n = 77) was recruited that served as the baseline for comparison.

Results

Baseline serum BDNF level in ECT group was lower than in controls (9.7 ± 2.1 vs. 12.4 ± 3.2 ng/ml; P < 0.001), but increased after ECT, such that there was no difference between the two groups (11.9 ± 3.3 vs. 12.4 ± 3.2 ng/ml; P = 0.362). There was no correlation between patients’ Positive and Negative Syndrome Scale (PANSS) score and serum BDNF level before ECT; however, a negative correlation was observed after ECT (total: r = −0.692; P < 0.01). From baseline to remission after ECT, serum BDNF level increased (P < 0.001) and their PANSS score decreased (P < 0.001). Changes in BDNF level (2.21 ± 4.10 ng/ml) and PANSS score (28.69 ± 14.96) were positively correlated in the ECT group (r = 0.630; P < 0.01).

Conclusions

BDNF level was lower in schizophrenia patients relative to healthy controls before ECT and medication. BDNF level increased after ECT and medication, and its longitudinal change was associated with changes in patients’ psychotic symptoms. These results indicate that BDNF mediates the antipsychotic effects of ECT.

Copyright

Corresponding author

Corresponding author at: Department of Psychiatry, Affiliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou 225003, PR China, zhangxiaobim@163.com.
⁎⁎Corresponding author at: Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500), Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, PR China, jijunwang27@163.com.

Footnotes

Hide All
1

These authors contributed equally to this work.

Footnotes

References

Hide All
[1]WHO. WHO health report 2001 – mental health: new understanding, new hope. World Health Organization; 2001. p. 3334.
[2]Pompili, M., Lester, D., Dominici, G., Longo, L., Marconi, G., Forte, A., et al.Indications for electroconvulsive treatment in schizophrenia: a systematic review. Schizophr Res 2013;146(1–3):19
[3]Rodriguez-Jimenez, R., Bagney, A., Torio, I., Caballero, M., Ruiz, P., Rivas, deP., et al.Clinical usefulness and economic implications of continuation/maintenance electroconvulsive therapy in a Spanish National Health System public hospital: a case series. Rev Psiquiatr Salud Ment 2015;8(2):7582
[4]Gao, J., Wang, W.Y., Mao, Y.W., Graff, J., Guan, J.S., Pan, L., et al.A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature 2010;466(7310):11051109
[5]Angelucci, F., Brene, S., Mathe, A.A.BDNF in schizophrenia, depression and corresponding animal models. Mol Psychiatry 2005;10(4):345352
[6]Kim, H.J., Song, B.K., So, B., Lee, O., Song, W., Kim, Y.Increase of circulating BDNF levels and its relation to improvement of physical fitness following 12 weeks of combined exercise in chronic patients with schizophrenia: a pilot study. Psychiatry Res 2014;220(3):792796
[7]Goggi, J., Pullar, I.A., Carney, S.L., Bradford, H.F.Signalling pathways involved in the short-term potentiation of dopamine release by BDNF. Brain Res 2003;968(1):156161
[8]Akyol, E.S., Albayrak, Y., Beyazyuz, M., Aksoy, N., Kuloglu, M., Hashimoto, K.Decreased serum levels of brain-derived neurotrophic factor in schizophrenic patients with deficit syndrome. Neuropsychiatr Dis Treat 11 2015 865872
[9]Reinhart, V., Bove, S.E., Volfson, D., Lewis, D.A., Kleiman, R.J., Lanz, T.A.Evaluation of TrkB and BDNF transcripts in prefrontal cortex, hippocampus, and striatum from subjects with schizophrenia, bipolar disorder, and major depressive disorder. Neurobiol Dis 2015;77:220227
[10]Leucht, S.Measurements of response, remission, and recovery in schizophrenia and examples for their clinical application. J Clin Psychiatry 2014;75(Suppl 1):814
[11]Gama, C.S., Andreazza, A.C., Kunz, M., Berk, M., Belmonte-de-Abreu, P.S., Kapczinski, F.Serum levels of brain-derived neurotrophic factor in patients with schizophrenia and bipolar disorder. Neurosci Lett 2007;420(1):4548
[12]Pedrini, M., Chendo, I., Grande, I., Lobato, M.I., Belmonte-de-Abreu, P.S., Lersch, C., et al.Serum brain-derived neurotrophic factor and clozapine daily dose in patients with schizophrenia: a positive correlation. Neurosci Lett 2011;491(3):207210
[13]Nordgren, M., Karlsson, T., Svensson, M., Koczy, J., Josephson, A., Olson, L., et al.Orchestrated regulation of Nogo receptors, LOTUS, AMPA receptors and BDNF in an ECT model suggests opening and closure of a window of synaptic plasticity. PLoS ONE 2013;8(11):pe78778
[14]Segawa, M., Morinobu, S., Matsumoto, T., Fuchikami, M., Yamawaki, S.Electroconvulsive seizure, but not imipramine, rapidly up-regulates pro-BDNF and t-PA, leading to mature BDNF production, in the rat hippocampus. Int J Neuropsychopharmacol 2013;16(2):339350
[15]Melkerson, M., editor. Administration, FaD, special premarket 510(k) notification for NeuroStar TMS therapy system for major depressive disorderxps.
[16]Zakharyan, R., Boyajyan, A.Brain-derived neurotrophic factor blood levels are decreased in schizophrenia patients and associate with rs6265 genotypes. Clin Biochem 2014;47(12):10521055
[17]Jindal, R.D., Pillai, A.K., Mahadik, S.P., Eklund, K., Montrose, D.M., Keshavan, M.S.Decreased BDNF in patients with antipsychotic naive first episode schizophrenia. Schizophr Res 1191–32010 4751
[18]Ray, M.T., Shannon Weickert, C., Webster, M.J.Decreased BDNF and TrkB mRNA expression in multiple cortical areas of patients with schizophrenia and mood disorders. Transl Psychiatry 4 2014 pe389
[19]Weickert, C.S., Hyde, T.M., Lipska, B.K., Herman, M.M., Weinberger, D.R., Kleinman, J.E.Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia. Mol Psychiatry 2003;8(6):592610
[20]Tunca, Z., Kivircik Akdede, B., Ozerdem, A., Alkin, T., Polat, S., Ceylan, D., et al.Diverse glial cell line-derived neurotrophic factor (GDNF) support between mania and schizophrenia: a comparative study in four major psychiatric disorders. Eur Psychiatry 2015;30(2):198204
[21]Silver, H., Mandiuk, N., Einoch, R., Susser, E., Danovich, L., Bilker, W., et al.Improvement in verbal memory following SSRI augmentation of antipsychotic treatment is associated with changes in the expression of mRNA encoding for the GABA-A receptor and BDNF in PMC of schizophrenic patients. Int Clin Psychopharmacol 2015;30(3):158166
[22]Silver, H., Susser, E., Danovich, L., Bilker, W., Youdim, M., Goldin, V., et al.SSRI augmentation of antipsychotic alters expression of GABA(A) receptor and related genes in PMC of schizophrenia patients. Int J Neuropsychopharmacol 2011;14(5):573584
[23]Tan, Q.R., Wang, X.Z., Wang, C.Y., Liu, X.J., Chen, Y.C., Wang, H.H., et al.Differential effects of classical and atypical antipsychotic drugs on rotenone-induced neurotoxicity in PC12 cells. Eur Neuropsychopharmacol 2007;17(12):768773
[24]Park, S.W., Lee, C.H., Cho, H.Y., Seo, M.K., Lee, J.G., Lee, B.J., et al.Effects of antipsychotic drugs on the expression of synaptic proteins and dendritic outgrowth in hippocampal neuronal cultures. Synapse 2013;67(5):224234
[25]Fumagalli, F., Molteni, R., Racagni, G., Riva, M.A.Stress during development: impact on neuroplasticity and relevance to psychopathology. Prog Neurobiol 2007;81(4):197217
[26]Szyf, M.DNA methylation, the early-life social environment and behavioral disorders. J Neurodev Disord 2011;3(3):238249
[27]Luoni, A., Berry, A., Calabrese, F., Capoccia, S., Bellisario, V., Gass, P., et al.Delayed BDNF alterations in the prefrontal cortex of rats exposed to prenatal stress: preventive effect of lurasidone treatment during adolescence. Eur Neuropsychopharmacol 2014;24(6):986995
[28]Schloesser, R.J., Orvoen, S., Jimenez, D.V., Hardy, N.F., Maynard, K.R., Sukumar, M., et al.Antidepressant-like effects of electroconvulsive seizures require adult neurogenesis in a neuroendocrine model of depression. Brain Stimul 2015;8(5):862867
[29]Newton, S.S., Girgenti, M.J., Collier, E.F., Duman, R.S.Electroconvulsive seizure increases adult hippocampal angiogenesis in rats. Eur J Neurosci 2006;24(3):819828
[30]Ongur, D., Pohlman, J., Dow, A.L., Eisch, A.J., Edwin, F., Heckers, S., et al.Electroconvulsive seizures stimulate glial proliferation and reduce expression of Sprouty2 within the prefrontal cortex of rats. Biol Psychiatry 2007;62(5):505512
[31]Chen da, C., Wang, J., Wang, B., Yang, S.C., Zhang, C.X., Zheng, Y.L., et al.Decreased levels of serum brain-derived neurotrophic factor in drug-naive first-episode schizophrenia: relationship to clinical phenotypes. Psychopharmacology (Berl) 2009;207(3):375380
[32]Xiu, M.H., Hui, L., Dang, Y.F., Hou, T.D., Zhang, C.X., Zheng, Y.L., et al.Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics. Prog Neuropsychopharmacol Biol Psychiatry 2009;33(8):15081512
[33]Favalli, G., Li, J., Belmonte-de-Abreu, P., Wong, A.H., Daskalakis, Z.J.The role of BDNF in the pathophysiology and treatment of schizophrenia. J Psychiatr Res 2012;46(1):111
[34]Buckley, P.F., Pillai, A., Howell, K.R.Brain-derived neurotrophic factor: findings in schizophrenia. Curr Opin Psychiatry 2011;24(2):122127
[35]Han, B., Zhang, X.Y., Wang, D.Y., Ren, W.W., Gu, Y.Y., Zhu, L., et al.Serum brain-derived neurotrophic factor levels and psychotic symptoms in heroin dependence. Compr Psychiatry 2015;62:8085
[36]Li, W., Zhou, N., Yu, Q., Li, X., Yu, Y., Sun, S., et al.Association of BDNF gene polymorphisms with schizophrenia and clinical symptoms in a Chinese population. Am J Med Genet B Neuropsychiatr Genet 2013;162B(6):538545
[37]Whalley, H.C., Baig, B.J., Hall, J., Job, D.E., McIntosh, A.M., Cunningham-Owens, D.G., et al.Effects of the BDNF val66met polymorphism on prefrontal brain function in a population at high genetic risk of schizophrenia. Am J Med Genet B: Neuropsychiatr Genet 2010;153B(8):14741482
[38]Krebs, M.O., Guillin, O., Bourdel, M.C., Schwartz, J.C., Olie, J.P., Poirier, M.F., et al.Brain Derived Neurotrophic Factor (BDNF) gene variants association with age at onset and therapeutic response in schizophrenia. Mol Psychiatry 2000;5(5):558562
[39]Altar, C.A., Whitehead, R.E., Chen, R., Wörtwein, G., Madsen, T.M.Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain. Biol Psychiatry 2003;54(7):703709
[40]Martinotti, G., Ricci, V., Di Nicola, M., Caltagirone, C., Bria, P., Angelucci, F.Brain-derived neurotrophic factor and electroconvulsive therapy in a schizophrenic patient with treatment-resistant paranoid-hallucinatory symptoms. J ECT 2011;27(1):pe44pe46
[41]Lee, A.H., Lange, C., Ricken, R., Hellweg, R., Lang, U.E.Reduced brain-derived neurotrophic factor serum concentrations in acute schizophrenic patients increase during antipsychotic treatment. J Clin Psychopharmacol 2011;31(3):334336
[42]Reis, H.J., Nicolato, R., Barbosa, I.G., Teixeira do Prado, P.H., Romano-Silva, M.A., Teixeira, A.L.Increased serum levels of brain-derived neurotrophic factor in chronic institutionalized patients with schizophrenia. Neurosci Lett 2008;439(2):157159
[43]Fernandes, B.S., Steiner, J., Berk, M., Molendijk, M.L., Gonzalez-Pinto, A., Turck, C.W., et al.Brain-derived neurotrophic factor and antidepressive effect of electroconvulsive therapy: systematic review and meta-analyses of the preclinical and clinical literature. PLOS ONE 2015;10(11):pe0141564
[44]Taylor, S.M.Electroconvulsive therapy, brain-derived neurotrophic factor, and possible neurorestorative benefit of the clinical application of electroconvulsive therapy. J ECT 2008;24(2):160165
[45]Piccinni, A., Del Debbio, A., Medda, P., Bianchi, C., Roncaglia, I., Veltri, A., et al.Plasma Brain-Derived Neurotrophic Factor in treatment-resistant depressed patients receiving electroconvulsive therapy. Eur Neuropsychopharmacol 2009;19(5):349355
[46]Hu, Y.D., Yu, X., Yang, F.D., Si, T.M., Wang, W.D., Tan, Y.L., et al.The level of serum brain-derived neurotrophic factor is associated with the therapeutic efficacy of modified electroconvulsive therapy in Chinese patients with depression. J ECT 2010;26(2):121125
[47]Fernandes, B., Gama, C.S., Massuda, R., Torres, M., Camargo, D., Kunz, M., et al.Serum brain-derived neurotrophic factor (BDNF) is not associated with response to electroconvulsive therapy (ECT): a pilot study in drug resistant depressed patients. Neurosci Lett 2009;453(3):195198
[48]Kaija, H., Sami, A., Martti, H., Esa, L., Riikka, R., Kari, M., et al.Brain-derived neurotrophic factor (BDNF) polymorphisms G196A and C270T are not associated with response to electroconvulsive therapy in major depressive disorder. Eur Arch Psychiatry Clin Neurosci 2006;257(1):3135
[49]Rapinesi, C., Kotzalidis, G.D., Curto, M., Serata, D., Ferri, V.R., Scatena, P., et al.Electroconvulsive therapy improves clinical manifestations of treatment-resistant depression without changing serum BDNF levels. Psychiatry Res 2272–32015 171178
[50]Hyman, C.H.M., Barde, Y.A., Juhasz, M., Yancopoulos, G.D., Squinto, S.P., Lindsay, F. R.M.BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350 1991
[51]HT. Neurotrophins and neuronal plasticity Science. 1995;270:6.

Keywords

Increased serum brain-derived neurotrophic factor levels following electroconvulsive therapy or antipsychotic treatment in patients with schizophrenia

  • J. Li (a1) (a2) (a3), F. Ye (a2), W. Xiao (a2), X. Tang (a2), W. Sha (a2), X. Zhang (a2) and J. Wang (a1) (a3)...

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.

Increased serum brain-derived neurotrophic factor levels following electroconvulsive therapy or antipsychotic treatment in patients with schizophrenia

  • J. Li (a1) (a2) (a3), F. Ye (a2), W. Xiao (a2), X. Tang (a2), W. Sha (a2), X. Zhang (a2) and J. Wang (a1) (a3)...
Submit a response

Comments

No Comments have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *