Serum and plasma brain-derived neurotrophic factor and response in a randomized controlled trial of riluzole for treatment resistant depression

Kiselycznyk, Carly; Banasr, Mounira; Webler, Ryan; Haile, Colin N.; Mathew, Sanjay J.

doi:10.1016/j.jad.2018.08.075

Cited by 23 publications

(23 citation statements)

References 38 publications

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“…It has been speculated that wash-out periods may mask the expected reduced BDNF levels found in depression, as it is been proposed that antidepressants stimulate BDNF synthesis (Wilkinson et al, 2018). In fact, studies indicate that the reduction of BDNF is most consistently observed after a 4-week wash-out period (Brunoni et al, 2008; Yip et al, 2017) or in severe untreated patients (Kreinin et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, preclinical and clinical evidence suggest that patients with depression tend to present lower levels of serum BDNF when compared to healthy individuals (Wilkinson et al, 2018; Ma et al, 2019), which may be reversed after antidepressant drug treatment (Brunoni et al, 2017; Molendijk et al, 2018). Baseline alterations in serum BDNF levels in depressive patients is not a consensus in the literature (Jevtović et al, 2011; Molendijk et al, 2011; Papakostas et al, 2011; Elfving et al, 2012) and changes in BDNF levels after treatment seem to depend on the antidepressant class (Kreinin et al, 2015; Sheldrick et al, 2017; Wilkinson et al, 2018). Nevertheless, novel antidepressants including agomelatine and vortioxetine were found to increase hippocampal BDNF level and of BDNF positive neurons in an animal model of depression (Lu et al, 2018a,b).…”

Section: Introductionmentioning

confidence: 99%

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Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial

et al. 2019

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Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatmentresistant depression. Preclinical and clinical studies have suggested that serum brainderived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls (N = 45) and patients with treatment-resistant depression (N = 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia. Moreover, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca (N = 35) when compared to placebo (N = 34). Furthermore, at D2 just patients treated with ayahuasca (N = 14), and not with placebo (N = 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms. This is the first double-blind randomized placebo-controlled clinical trial that explored the modulation of BDNF in response to a psychedelic in patients with depression. The results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelics as an antidepressant. This trial is registered at http://clinicaltrials.gov (NCT02914769).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial

et al. 2019

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“…This result suggests that resveratrol may have the effect of treating depression. BDNF is a member of the neurotrophic factor family, which has the effect of promoting proliferation and differentiation of neurons, promoting neuronal survival and development, altering neuronal morphology in the brain, increasing synaptic terminal density, and promoting dendritic and axon growth ( 14 ). NPY is a known neuroendocrine polypeptide that plays an important regulatory role in neuronal excitability ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effect of resveratrol on mice with depression

Chu

Han

2019

Exp Ther Med

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The effect and mechanism of resveratrol on depression-like behavior in mice with depression were investigated. A mouse model of depression was established by social isolation combined with chronic unpredictable stress. The mice were randomly divided into the control group, the model group, the low dose group, the medium dose group and the high dose group. The rats in the low, medium and high dose groups were intraperitoneally injected with resveratrol 10, 20 and 30 mg/kg, respectively. The control and model groups were intraperitoneally injected with an equal volume of normal saline. After 21 days of continuous treatment, the neurobehavioral changes of each group were analyzed by forced swimming test, tail suspension experiment and sucrose consumption experiment. Dopamine (DA) and serotoni (5-HT) and the level of brain-derived nerve growth factor (BDNF) in the prefrontal cortex of each group were analyzed by ELISA. The level of neuropeptide (NPY) expression was analyzed by western blot analysis. Compared with the model group, the immobility time of the tail suspension experiment and forced swimming experiment in the low, medium and high dose groups was significantly prolonged (P<0.05), while the 24 h sucrose consumption was significantly increased (P<0.05), showing a dose-dependent manner. Compared with the model group, the levels of DA and 5-HT in the prefrontal cortex of the low, medium and high dose groups were significantly increased, and showed a dose-dependent effect (P<0.05). Compared with the model group, the expression levels of NPY protein in the low, medium and high dose groups were significantly increased, and gradually increased with the increase of the dose, the difference was statistically significant (P<0.05). Resveratrol can significantly increase the levels of neurotransmitters DA and 5-HT in the prefrontal cortex and increase the expression of NPY in the brain, which can play an antagonistic role in depression.

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“…ProBDNF-p75NTR also interferes with neurotransmitter release and inhibits axonal outgrowth ( 61 ). A series of reports demonstrated that serum BDNF in depressive patients is significantly lower than that observed in the healthy population ( 62 – 64 ). However, few studies report the expression of mBDNF and proBDNF in patients with SCAD with co-morbid depression.…”

Section: Discussionmentioning

confidence: 96%

Serum Levels of FGF21, β-Klotho, and BDNF in Stable Coronary Artery Disease Patients With Depressive Symptoms: A Cross-Sectional Single-Center Study

Chen

Duan

et al. 2021

Front. Psychiatry

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Background: The incidence of depressive symptoms (DS) in patients with stable coronary artery disease (SCAD) is significantly higher than those in healthy population, and that DS are independent risk factors for cardiovascular events. Previous studies have reported that fibroblast growth factor 21 (FGF21), β-klotho, mature brain-derived neurotrophic factor (mBDNF), and BDNF precursor (proBDNF) play important roles in the pathogenesis and treatment of coronary heart disease and depression. With this in mind, the present study aimed to clarify the relationship between FGF21, β-klotho, mBDNF, and proBDNF and SCAD with comorbid depression, in addition to also exploring the underlying mechanisms of these disease processes.Methods: A total of 116 patients with SCAD and 45 healthy controls were recruited. Patients with SCAD were further divided into two subgroups based on the Zung Self-Rating Depression Scale (SDS), which were characterized as those with no DS (NDS) and those with DS. Baseline data were collected, and serum levels of FGF21, β-klotho, mBDNF, and proBDNF were determined.Results: In SCAD patients, Gensini scores—denoting the degree of coronary arteriostenosis—were significantly greater in the DS group than in the NDS group. There was also a positive correlation between the Gensini scores and the SDS scores. Patients in the SCAD group demonstrated a lower serum FGF21. Serum β-klotho, mBDNF, and mBDNF/proBDNF were also significantly lower in the DS group than in the NDS group. Furthermore, β-klotho and mBDNF were negatively correlated with the SDS scores. Additionally, SCAD patients were divided into lower- and higher-level groups using hierarchical cluster analysis, with the results highlighting that patients in the lower mBDNF group had a higher incidence of DS.Conclusions: The depression score was positively correlated with the severity of coronary artery stenosis, and serum FGF21, β-klotho, mBDNF, and proBDNF were closely related to the development of DS in patients with SCAD. These observations suggest FGF21, β-klotho, mBDNF, and proBDNF as potential diagnostic and/or therapeutic targets for SCAD with co-morbid depression.

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Serum and plasma brain-derived neurotrophic factor and response in a randomized controlled trial of riluzole for treatment resistant depression

Abstract: Preliminary evidence reported here suggests that lower baseline BDNF may be associated with better clinical response to riluzole.

Cited by 23 publications

References 38 publications

Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial

Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial

Therapeutic effect of resveratrol on mice with depression

Serum Levels of FGF21, β-Klotho, and BDNF in Stable Coronary Artery Disease Patients With Depressive Symptoms: A Cross-Sectional Single-Center Study

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