- •Plasma BDNF levels do not differ between controls and patients with depression.
- •Plasma BDNF levels do not change following a course of ECT.
- •Patients with Val/Met or Met/Met genotype have higher BDNF levels than Val/Val.
- •Plasma BDNF levels are not related to depression symptom severity.
- •Plasma BDNF levels are not associated with the therapeutic response to ECT.
Brain derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression and the antidepressant response. Electroconvulsive therapy (ECT) is reported to increase BDNF levels in blood, though only a small number of studies have been conducted to date.
Our objectives were to: 1) compare plasma BDNF levels in medicated patients with depression and controls; 2) assess the effect of ECT on plasma BDNF levels in medicated patients with depression; 3) explore the relationship between plasma BDNF levels and the Val66Met (rs6265) BDNF polymorphism; and 4) examine the relationship between plasma BDNF levels and clinical symptoms and outcomes with ECT.
Plasma BDNF levels were analyzed in samples from 61 medicated patients with a major depressive episode and 50 healthy controls, and in patient samples following a course of ECT. Fifty-two samples from the depressed patient group were genotyped for the Val66Met BDNF polymorphism.
There was no difference in plasma BDNF levels between the control and depressed groups, and there was no difference in plasma BDNF levels in patients following treatment with ECT. In line with previous reports, we show that, in medicated patients with depression, Met-carriers had higher plasma BDNF levels than Val-carriers, though genotype was not related to clinical response. We found no association between plasma BDNF levels and depression severity or the clinical response to ECT.
Our results suggest that plasma BDNF does not represent a suitable candidate biomarker for determining the therapeutic response to ECT.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Depression and other common mental disorders: global Health estimates.2017
- Depression is the leading cause of disability around the world.J Am Med Assoc. 2017; 1517: 317
- A neurotrophic model for stress-related mood disorders.Biol Psychiatr. 2006; 59: 1116-1127
- BDNF: a key factor with multipotent impact on brain signaling and synaptic plasticity.Cell Mol Neurobiol. 2018; 38: 579-593
- Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus.J Neurosci. 1995; 15: 1768-1777
- Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments.J Neurosci. 1995; 15: 7539-7547
- Reduced platelet BDNF level in patients with major depression.Prog Neuro-Psychopharmacol Biol Psychiatry. 2009; 33: 849-853
- Decreased plasma BDNF level in depressive patients.J Affect Disord. 2007; 101: 239-244
- Brain-derived neurotrophic factor (BDNF) changes in the serum of depressed women.Prog Neuro-Psychopharmacol Biol Psychiatry. 2006; 30: 1256-1260
- Serum and plasma BDNF levels in major depression: a replication study and meta-analyses.World J Biol Psychiatr. 2010; 11: 763-773
- Reduced cerebrospinal fluid levels of brain-derived neurotrophic factor is associated with cognitive impairment in late-life major depression.J Gerontol B Psychol Sci Soc Sci. 2014; 69: 845-851
- Decreased BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders.J Psychiatry Neurosci. 2011; 36: 195-203
- Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder.Am J Psychiatr. 2012; 169: 1194-1202
- Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication.Biol Psychiatr. 2001; 50: 260-265
- Effect of mirtazapine treatment on serum levels of brain-derived neurotrophic factor and tumor necrosis factor-alpha in patients of major depressive disorder with severe depression.Pharmacology. 2016; 97: 184-188
- 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 (e0141564)
- Serum BDNF levels before treatment predict SSRI response in depression.Prog Neuro-Psychopharmacol Biol Psychiatry. 2011; 35: 1623-1630
- A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression.Int J Neuropsychopharmacol. 2008; 11: 1169-1180
- Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484).Mol Psychiatr. 2014; 19: 791-800
- The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function.Cell. 2003; 112: 257-269
- Interaction between stress and the BDNF Val66Met polymorphism in depression: a systematic review and meta-analysis.BMC Med. 2014; 7: 12
- Meta-analysis of BDNF Val66Met polymorphism association with treatment response in patients with major depressive disorder.Eur Neuropsychopharmacol. 2010; 20: 535-544
- Efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (rTMS) versus electroconvulsive therapy (ECT) for major depression: a systematic review and meta-analysis of randomized trials.Depress Anxiety. 2013; 30: 614-623
- UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis.Lancet. 2003; 361: 799-808
- Molecular and cellular actions of chronic electroconvulsive seizures.J ECT. 1998; 14: 181-193
- Neurophysiological mechanisms of electroconvulsive therapy for depression.Neurosci Res. 2009; 64: 3-11
- Immune and neurotrophin stimulation by electroconvulsive therapy: is some inflammation needed after all?.Transl Psychiatry. 2015; 5 (e609)
- Electroconvulsive stimulation alters levels of BDNF-associated microRNAs.Neurosci Lett. 2013; 549: 125-129
- Effects of brief pulse and ultrabrief pulse electroconvulsive stimulation on rodent brain and behaviour in the corticosterone model of depression.Int J Neuropsychopharmacol. 2014; 17: 1477-1486
- Electroconvulsive seizures regulate gene expression of distinct neurotrophic signaling pathways.J Neurosci. 2004; 24: 2667-2677
- Antidepressant-induced neurogenesis in the hippocampus of adult nonhuman primates.J Neurosci. 2007; 27: 4894-4901
- Increased BDNF levels after electroconvulsive therapy in patients with major depressive disorder: a meta-analysis study.J Psychiatr Res. 2016; 83: 47-53
- BDNF blood levels after electroconvulsive therapy in patients with mood disorders: a systematic review and meta-analysis.World J Biol Psychiatr. 2014; 15: 411-418
- Meta-analyses of comparative efficacy of antidepressant medications on peripheral BDNF concentration in patients with depression.PLoS One. 2017; 12 (e0172270)
- World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.J Am Med Assoc. 2013; 310: 2191-2194
- Bitemporal versus high-dose unilateral twice-weekly electroconvulsive therapy for depression (EFFECT-Dep): a pragmatic, randomized, non-inferiority trial.Am J Psychiatr. 2016; 173: 408-417
- Electroconvulsive therapy modulates plasma pigment epithelium-derived factor in depression: a proteomics study.Transl Psychiatry. 2017; 7 (e1073)
- Structured clinical Interview for DSM-IV Axis I disorders, clinician version (SCID-CV).American Psychiatric Press, Washington DC1996
- Hamilton rating scale for depression, ECDEU version used in the treatment of depression collaborative Research program. Handbook of depression-treatment, assessment and Research.The Dorsey Press, Homewood1985
- Serum brain-derived neurotrophic factor level is increased and associated with obesity in newly diagnosed female patients with type 2 diabetes mellitus.Metabolism. 2006; 55: 852-857
- Increased plasma brain-derived neurotrophic factor levels in chronic smokers following unaided smoking cessation.Neurosci Lett. 2007; 423: 53-57
- Association between obesity and psychiatric disorders in the US adult population.Arch Gen Psychiatr. 2006; 63: 824-830
- Smoking and major depression. A causal analysis.Arch Gen Psychiatr. 1993; 50: 36-43
- Ethnic difference of the BDNF 196G/A (val66met) polymorphism frequencies: the possibility to explain ethnic mental traits.Am J Med Genet B Neuropsychiatr Genet. 2004; 126B: 122-123
- Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity.Mol Psychiatr. 2010; 15: 260-271
- The Met allele of the BDNF Val66Met polymorphism is associated with increased BDNF serum concentrations.Mol Psychiatr. 2009; 14: 120-122
- The BDNF Val66Met polymorphism impacts parahippocampal and amygdala volume in healthy humans: incremental support for a genetic risk factor for depression.Psychol Med. 2009; 39: 1831-1839
- Plasma BDNF concentration, Val66Met genetic variant and depression-related personality traits.Gene Brain Behav. 2010; 9: 512-518
- Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity.Biol Psychiatr. 2005; 57: 1068-1072
- Low plasma BDNF is associated with suicidal behavior in major depression.Prog Neuro-Psychopharmacol Biol Psychiatry. 2007; 31: 78-85
- Plasma and serum brain-derived neurotrophic factor (BDNF) in depressed patients during 1 year of antidepressant treatments.J Affect Disord. 2008; 105: 279-283
- Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants.Biol Psychiatr. 2003; 54: 70-75
- Serum levels of brain-derived neurotrophic factor in major depressive disorder: state-trait issues, clinical features and pharmacological treatment.Mol Psychiatr. 2011; 16: 1088-1095
- The impact of age, weight and gender on BDNF levels in human platelets and plasma.Neurobiol Aging. 2005; 26: 115-123
- Electroconvulsive therapy improves clinical manifestation with plasma BDNF levels unchanged in treatment-resistant depression patients.Neuropsychobiology. 2013; 68: 110-115
- Increased plasma concentration of brain-derived neurotrophic factor with electroconvulsive therapy: a pilot study in patients with major depression.J Clin Psychiatr. 2007; 68: 512-517
- Plasma brain-derived neurotrophic factor in treatment-resistant depressed patients receiving electroconvulsive therapy.Eur Neuropsychopharmacol. 2009; 19: 349-355
- Additional ECT increases BDNF-levels in patients suffering from major depressive disorders compared to patients treated with citalopram only.J Psychiatr Res. 2013; 47: 908-915
- Electroconvulsive therapy (ECT) and aerobic exercise training (AET) increased plasma BDNF and ameliorated depressive symptoms in patients suffering from major depressive disorder.J Psychiatr Res. 2016; 76: 1-8
- Plasma brain-derived neurotrophic factor daily variations in men: correlation with cortisol circadian rhythm.J Endocrinol. 2008; 197: 429-435
- Genetic association study of BDNF in depression: finding from two cohort studies and a meta-analysis.Am J Med Genet B Neuropsychiatr Genet. 2008; 147B: 814-821
- Effects of COMT, DRD2, BDNF, and APOE genotypic variation on treatment efficacy and cognitive side effects of electroconvulsive therapy.J ECT. 2015; 31: 129-135
- Differences in cognitive outcomes after ECT depending on BDNF and COMT polymorphisms.J ECT. 2016; 32: 243-250
- Brain-derived neurotrophic factor (BDNF) polymorphisms G196A and C270T are not associated with response to electroconvulsive therapy in major depressive disorder.Eur Arch Psychiatr Clin Neurosci. 2007; 257: 31-35
- Plasma BDNF level in major depression: biomarker of the Val66Met BDNF polymorphism and of the clinical course in Met Carrier patients.Neuropsychobiology. 2017; 75: 39-45
- Val66Met polymorphism association with serum BDNF and inflammatory biomarkers in major depression.World J Biol Psychiatr. 2017; : 1-8
- Brain-derived neurotrophic factor Val66Met polymorphism association with antidepressant efficacy: a systematic review and meta-analysis.Asia Pac Psychiatr. 2014; 6: 241-251
- Correlations and discrepancies between serum and brain tissue levels of neurotrophins after electroconvulsive treatment in rats.Pharmacopsychiatry. 2009; 42: 270-276
- Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF.Brain Res Mol Brain Res. 1996; 36: 280-286
- Enzyme-linked immunosorbent assay for detection of Plasmodium falciparum histidine-rich protein 2 in blood, plasma, and serum.Clin Vaccine Immunol. 2008; 15: 1012-1018
- USDHHS FDA Center for Drug Evaluation and Research. Guidance for industry: bioanalytical method validation. 2001 (Available from:)
Published online: May 18, 2018
Accepted: May 15, 2018
Received in revised form: April 30, 2018
Received: January 19, 2018
© 2018 Elsevier Inc. All rights reserved.