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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: BACKGROUND:Serum brain-derived neurotrophic factor (BDNF) is decreased in individuals with major depressive disorder (MDD). Pre-clinical and clinical reports suggest that the glutamate release inhibitor riluzole increases BDNF and may have antidepressant properties. Here we report serum (sBDNF) and plasma (pBDNF) levels from a randomized controlled, adjunctive, sequential parallel comparison design trial of riluzole in MDD. METHODS:Serum and plasma BDNF samples were drawn at baseline and weeks 6 and 8 from 55 subjects randomized to adjunctive treatment with riluzole or placebo for 8 weeks. RESULTS:Riluzole responders had lower baseline serum (19.08?ng/ml [SD 9.22] v. 28.80?ng/ml [9.63], p?=?0.08) and plasma (2.72?ng/ml [1.07] v. 4.60?ng/ml [1.69], p?=?0.06) BDNF compared to non-responders at a trend level. This pattern was nominally seen in placebo responders for baseline pBDNF to some degree (1.21?ng/ml [SD 1.29] v. 3.58?ng/ml [SD 1.67], p?=?0.12) but not in baseline sBDNF. LIMITATIONS:A number of limitations warrant comment, including the small sample size of viable BDNF samples and the small number of riluzole responders. CONCLUSIONS:Preliminary evidence reported here suggests that lower baseline BDNF may be associated with better clinical response to riluzole.

SUBMITTER: Wilkinson ST

PROVIDER: S-EPMC6140345 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Wilkinson Samuel T ST Kiselycznyk Carly C Banasr Mounira M Webler Ryan D RD Haile Colin C Mathew Sanjay J SJ

Journal of affective disorders 20180818

<h4>Background</h4>Serum brain-derived neurotrophic factor (BDNF) is decreased in individuals with major depressive disorder (MDD). Pre-clinical and clinical reports suggest that the glutamate release inhibitor riluzole increases BDNF and may have antidepressant properties. Here we report serum (sBDNF) and plasma (pBDNF) levels from a randomized controlled, adjunctive, sequential parallel comparison design trial of riluzole in MDD.<h4>Methods</h4>Serum and plasma BDNF samples were drawn at basel ...[more]

PMID: 30153634

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Project description:Objectives: Brain-derived neurotrophic factor (BDNF) plays a role in cognition and metabolism. Specific nutrients can affect fasting BDNF concentrations, which are potentially mediated by insulin and/or glucose. Since macronutrients trigger each a different insulin and glucose response, we examined postprandial effects of meals rich in fat, carbohydrates, or protein on BDNF concentrations. BDNF was analyzed in serum and plasma, since concentration differences can be found between matrices. Methods: Healthy overweight/obese male participants (n = 18) participated in this randomized, double-blind, cross-over trial consisting of three test days with 1 week wash-out periods. Either a high-fat (En% fat, carbohydrates, protein: 52.3, 39.2, 8.0), high-carbohydrate (En% 9.6, 81.5, 8.6) or high-protein meal (En% 10.6, 51.5, 36.9) was consumed on each test day. BDNF concentrations were measured after 0, 60, and 240 min. Glucose and insulin concentrations were measured after 0, 15, 30, 45, 60, 90, 120, and 240 min. Results: BDNF concentrations were higher in serum compared with plasma (P < 0.001). Postprandial BDNF concentrations in serum decreased significantly after the high-fat (P = 0.013) and high-carbohydrate meals (P = 0.040), and showed a trend after the high-protein meal (P = 0.076). No differences were found between meals (P = 0.66). Postprandial BDNF concentrations measured in plasma did not significantly change after the different meals (P = 0.47). As total area under the curve (AUC) for glucose was significantly higher after the high-carbohydrate meal compared with the high-fat (P = 0.003) and high-protein meals (P < 0.001), and the total AUC for insulin was higher after the high-carbohydrate (P < 0.001) and high-protein meals (P < 0.001) compared with the high-fat meal, it seems that acute changes in glucose and insulin do not affect postprandial BDNF concentrations. However, after the high-protein meal, the higher total AUC for glucose correlated with lower serum BDNF concentrations, and a higher maximal increase in glucose correlated with a lower maximal increase in plasma BDNF concentrations. There were no correlations with insulin concentrations after either meal. Conclusion: Serum BDNF concentrations were higher than plasma concentrations. Since postprandial BDNF responses were not different between the meals, we conclude that there is no role for insulin or glucose in regulating postprandial BDNF concentrations. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03139890].

Dataset Information

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

Publications

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

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