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Lower serum brain-derived neurotrophic factor levels are associated with failure to achieve remission in patients with major depression after escitalopram treatment

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      Abstract

      BackgroundRemission, the primary goal of treatment for major depressive disorder (MDD), is the absence of significant signs or symptoms and the return to a state of normal functioning. A recent study found that the level of brain-derived neurotrophic factor (BDNF) increased after antidepressant treatment in remitted patients. This study evaluated serum BDNF levels in MDD patients with chronic maintenance treatment, and compared these between remission and nonremission groups.Materials and methodsSerum BDNF levels were measured in 34 MDD patients and 35 healthy controls. The severity of depression was measured using the Hamilton Depression Rating Scale (Ham-D). The MDD patients were divided into remission and nonremission groups according to a cutoff total Ham-D score of either ≤7 or ≤6.ResultsSerum BDNF levels differed significantly between the remission, nonremission, and healthy control groups (P<0.05). The Bonferroni post hoc test confirmed that serum BDNF levels were significantly lower in the nonremission group than in the healthy-control group (P<0.05), but did not differ significantly between the remission and healthy-control groups.LimitationsThis study included a small sample, and measured serum BDNF levels in the MDD patients at only one point during the maintenance treatment.ConclusionThis study found that serum BDNF levels during maintenance treatment were lower in MDD patients with failure to achieve remission than in controls, while the remitted subjects had normalized serum BDNF levels. A lower level of serum BDNF during maintenance treatment is associated with failure to achieve remission in patients with major depression. Moreover, serum BDNF levels after chronic antidepressant treatment can be used as a biological marker for detecting nonremission.

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      Most cited references 23

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      Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications.

      Converging lines of evidence implicate the neurotrophin brain-derived neurotrophic factor (BDNF) in the pathophysiology of major depression. Recent studies have begun to explore the relationship between serum BDNF and depression. We conducted meta-analyses of 11 studies examining differences in serum BDNF content between depressed and nondepressed subjects (N = 748), and eight studies comparing pre- and post-antidepressant treatment serum BDNF content (N = 220). The meta-analysis revealed strong evidence that BDNF levels were lower in depressed subjects than healthy control subjects (p < 6.8 x 10(-8)). Similarly, the second meta-analysis found significantly higher BDNF levels after antidepressant treatment (p = .003). There was no evidence of publication bias in the first (p = .376) or second (p = .571) meta-analysis and no evidence that either meta-analysis was unduly influenced by any one study. These findings provide strong evidence to suggest that serum BDNF levels are abnormally low in patients suffering from major depressive disorder and that the BDNF levels are elevated following a course of antidepressant treatment. Although the relationship of our findings to pathophysiology of depression and the mechanism of drug action remains to be determined, the measure may have potential use as a biomarker for psychiatric disorders or as a predictor of antidepressant efficacy.
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        Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence.

        In 1988, the MacArthur Foundation Research Network on the Psychobiology of Depression convened a task force to examine the ways in which change points in the course of depressive illness had been described and the extent to which inconsistency in these descriptions might be impeding research on this disorder. We found considerable inconsistency across and even within research reports and concluded that research on depressive illness would be well served by greater consistency in the definition change points in the course of illness. We propose an internally consistent, empirically defined conceptual scheme for the terms remission, recovery, relapse, and recurrence. In addition, we propose tentative operational criteria for each term. Finally, we discuss ways to assess the usefulness of such operational criteria through reanalysis of existing data and the design and conduct of new experiments.
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          A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression.

          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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            Author and article information

            Affiliations
            [1 ]Department of Psychiatry, Gangnam Eulji Hospital, Eulji University, Seoul, South Korea
            [2 ]Department of Psychiatry, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, South Korea
            [3 ]Department of Laboratory Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, South Korea
            Author notes
            Correspondence: Young-Min Park, Department of Psychiatry, Ilsan Paik Hospital, Inje University College of Medicine, 2240 Daehwa-Dong, Ilsansu-ku, Goyang, Gyeonggi-do 411-706, South Korea, Tel +82 31 910 7260, Fax +82 31 910 7268, Email medipark@ 123456hanmail.net
            Journal
            Neuropsychiatr Dis Treat
            Neuropsychiatr Dis Treat
            Neuropsychiatric Disease and Treatment
            Neuropsychiatric Disease and Treatment
            Dove Medical Press
            1176-6328
            1178-2021
            2014
            23 July 2014
            : 10
            : 1393-1398
            4114913
            10.2147/NDT.S64913
            ndt-10-1393
            © 2014 Lee et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

            The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

            Categories
            Original Research

            Neurology

            remission, major depression, brain-derived neurotrophic factor

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