Serum Brain-Derived Neurotrophic Factor, Depression, and Antidepressant Medications: Meta-Analyses and Implications

Sen, Srijan; Duman, Ronald S.; Sanacora, Gerard

doi:10.1016/j.biopsych.2008.05.005

Cited by 1,083 publications

(811 citation statements)

References 50 publications

(44 reference statements)

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“…Regardless, accruing data indicate a critical role of BDNF and neuroplasticity in the vulnerability to depression (Calabrese et al, 2009;Castren et al, 2010;Sen et al, 2008); many instances of depression are strongly linked with increased inflammatory cytokines (Haroon et al, 2012;Miller et al, 2009), and there is a likely interaction between BDNF and inflammatory cytokines (Lotrich, 2012). Herein, we report that lower BDNF levels (and the Val/Met polymorphisms rs6265) can increase susceptibility to subsequent inflammatory cytokine-associated depression.…”

Section: Discussionmentioning

confidence: 72%

“…Thus, it is feasible that cytokine-induced decreases in BDNF may result in the depressogenic effects of inflammatory cytokines such as IFN-a. Consistent with this, several studies have associated low serum BDNF with MDD (Aydemir et al, 2006;BocchioChiavetto et al, 2006;Gervasoni et al, 2005;Hashimoto, 2010;Sen et al, 2008;Shimizu et al, 2003;Verhagen et al, 2010), which subsequently normalizes with antidepressant treatment (Castren and Rantamaki, 2010;Chen et al, 2001). Also, a functional polymorphism causing a change from valine (Val) to methionine (Met) may result in diminished BDNF secretion (Egan et al, 2003).…”

Section: Introductionmentioning

confidence: 84%

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Brain-Derived Neurotrophic Factor Serum Levels and Genotype: Association with Depression during Interferon-α Treatment

Lotrich

Albusaysi

Ferrell

2012

Neuropsychopharmacol

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Depression has been associated with inflammation, and inflammation may both influence and interact with growth factors such as brainderived neurotrophic factor (BDNF). Both the functional Val66Met BDNF polymorphism (rs6265) and BDNF levels have been associated with depression. It is thus plausible that decreased BDNF could mediate and/or moderate cytokine-induced depression. We therefore prospectively employed the Beck Depression Inventory-II (BDI-II), the Hospital Anxiety and Depression Scale (HADS), and the Montgomery-Asberg Depression Rating Scale (MADRS) in 124 initially euthymic patients during treatment with interferon-alpha (IFN-a), assessing serum BDNF and rs6265. Using mixed-effect repeated measures, lower pretreatment BDNF was associated with higher depression symptoms during IFN-a treatment (F 144,17.2 ¼ 6.8; Po0.0001). However, although the Met allele was associated with lower BDNF levels (F 1,83.0 ¼ 5.0; P ¼ 0.03), it was only associated with increased MADRS scores (F 4,8.9 ¼ 20.3; Po0.001), and not the BDI-II or HADS. An exploratory comparison of individual BDI-II items indicated that the Met allele was associated with suicidal ideation, sadness, and worthlessness, but not neurovegetative symptoms. Conversely, the serotonin transporter promoter polymorphism (5-HTTLPR) short allele was associated with neurovegetative symptoms such as insomnia, poor appetite and fatigue, but not sadness, worthlessness, or suicidal ideation. IFN-a therapy further lowered BDNF serum levels (F 4,37.7 ¼ 5.0; P ¼ 0.003), but this decrease occurred regardless of depression development. The findings thus do not support the hypothesis that decreasing BDNF is the primary pathway by which IFN-a worsens depression. Nonetheless, the results support the hypothesis that BDNF levels influence resiliency against developing inflammatory cytokine-associated depression, and specifically to a subset of symptoms distinct from those influenced by 5-HTTLPR. Neuropsychopharmacology (2013) 38, 985-995;

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Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 84%

Brain-Derived Neurotrophic Factor Serum Levels and Genotype: Association with Depression during Interferon-α Treatment

Lotrich

Albusaysi

Ferrell

2012

Neuropsychopharmacol

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“…Furthermore, there is strong evidence that peripheral growth factors, including BDNF, pro-inflammatory cytokines, endocrine factors, and metabolic markers contribute to the pathophysiology of major depressive disorder and antidepressant response (Schmidt et al, 2011). As a matter of fact BDNF levels are decreased in the blood of depressed patients and can be normalized with successful antidepressant treatment (Sen et al, 2008), although the origin and role of serum BDNF is unclear (Karege et al, 2005). Chronic peripheral administration of BDNF produces antidepressant and anxiolytic behavioral responses in animal models, increases the survival rate of newborn neurons, and increases BDNFmediated signaling in the adult hippocampus (Schmidt and Duman, 2010), an evidence that peripheral BDNF has functional actions within the brain and on behavior, and that serum BDNF may be a relevant biomarker for depression and treatment response.…”

Section: Introductionmentioning

confidence: 99%

Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats

Bahí

Chandrasekar

Dreyer

2014

Psychoneuroendocrinology

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Summary Several lines of evidences suggest that the brain-derived neutrophic factor (BDNF) is implicated in the pathophysiology of depression. However, the molecular mechanisms are not fully understood. In the current study we aimed to investigate how genetic modulation of BDNF in the hippocampus using microRNa124a (miR124a)-expressing lentiviral vectors (LV) might affect depression-like behavior in adult rats. For this purpose, we assessed the expression level of miR124a and its direct target BDNF in the hippocampus and the cortex after 21-days exposure to social defeat stress. Results demonstrated that miR124a was up-regulated in the hippocampus but not in the cortex. In contrast, and as expected, BDNF transcripts were down-regulated. In a different set of experiments, male Wistar rats received bilateral intra-hippocampal or intracortical infusions of BDNF-and miR124a-expressing lentiviral vectors and depression-like behavior was assessed after 21-days social defeat stress using the novelty suppressed feeding, the sucrose preference and the forced swim tests. The results indicated that miR124a overexpression exacerbated depression-like behavior. However, an anti-depressant like effect was observed when BDNF or miR124a-silencers (siR124a) were injected into the hippocampus. Importantly, when expressed into the cortex, LV-miR124a, LV-siR124a and LV-BDNF had no effect on depression. Our findings indicate that hippocampal miR124a and its direct target BDNF play an important role in depression-like behavior. Taken together, the current results reveal, for the first time, a potential molecular regulation of miR124a on BDNF, and the pronounced behavioral consequences of this regulation shed light on the mechanisms underlying BDNF anti-depressant potential. #

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“…Neurogenesis, resulting from either antidepressant treatment or cell implantation, attenuates depressive behavior (Tfilin et al, 2009). Depressed patients show reduced BDNF levels (Sen et al, 2008), which can result in lower number of dendrites in the synapse (Manji et al, 2003;Nestler et al, 2002). Antidepressants stimulate BDNF synthesis (Duman, 2004) and normalizes reduced BDNF levels in depressed patients (Brunoni et al, 2008;Sen et al, 2008).…”

Section: Cellular and Molecular Markersmentioning

confidence: 99%

Biological Alterations in Depression

Benton¹,

Wiltshire²

2011

Psychiatric Disorders - Trends and Developments

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Serum Brain-Derived Neurotrophic Factor, Depression, and Antidepressant Medications: Meta-Analyses and Implications

Abstract: Background-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.

Cited by 1,083 publications

References 50 publications

Brain-Derived Neurotrophic Factor Serum Levels and Genotype: Association with Depression during Interferon-α Treatment

Brain-Derived Neurotrophic Factor Serum Levels and Genotype: Association with Depression during Interferon-α Treatment

Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats

Biological Alterations in Depression

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