TY - JOUR

T1 - P.0408 Blood SIRT1 and BDNF dynamics in clinical trial of antidepressant action of resveratrol

AU - Zhanaeva, S. Y.

AU - Danilenko, K. V.

AU - Aftanas, L. I.

N1 - Supported by the Russian Science Foundation (grant no. 16-15-00128, 2016-2018 data acquisition) and budgetary funding for basic scientific research (theme No.AAAA-A21-121011990039-2 data analysis).

PY - 2021/12

Y1 - 2021/12

N2 - Background: We have previously reported the lack of efficacy of resveratrol (500 mg daily for 4 weeks) in the treatment of unipolar depression [1] as measured by the Hamilton Depression Rating Scale (HDRS-17). The second primary outcome measure in the study was a change in blood sirtuin-1 activity (clinicaltrials.gov # NCT03384329). The natural polyphenol flavonoid resveratrol is considered an activator of the antioxidant /cytoprotective enzyme SIRT1 [2] and is widely used in nutritional supplements [3]. Here we report the results of the effect of resveratrol on SIRT1 (activity, concentration, and expression in the blood) as well as on brain-derived neurotrophic factor (BDNF; an indicator of neuroplasticity and a potential biomarker of depression [4]). Methods: The recruited patients had to have major depressive disorder (MDD) or dysthymia, with melancholic features (DSM-5 criteria); HDRS-17 score at least 16; no antidepressant intake; absence of serious or unstable disease(s). Patients visited the clinic 5 times: on day -5 (selection), weeks 0 (inclusion), 2, 4 (during and after medication intake), and 6 (follow-up). The patients were administered to take randomly (1:1) resveratrol pill (Biotivia, USA) 500 mg daily in the morning or placebo pill, for 4 weeks (double-blind randomized placebo-controlled parallel-group design). Blood samples were taken at each post-selection visit between 12:00 and 13:00. The SIRT1 concentration (ng/ml) was assayed in serum by ELISA using the SIRT1 kit (MyBioSource, USA). Serum SIRT1 activity (units) was assayed by fluorometry of the enzyme kinetics using SIRT1 kit (Sigma-Aldrich, USA). SIRT1 gene expression (Ct value) was measured in whole blood (sampled in PaxGene tubes) by real-time PCR analysis. BDNF concentration in serum (pg/ml) was measured by xMAP technology on an analyser Luminex 200 using the Merck kit (Merck Millipore, USA). Each individual's serum samples were assayed in the same batch to avoid inter-assay variability. Results: Twenty-two patients completed the study (age ± SD 37.4 ± 9.7 years, range 23-59 years, 12 females), 11 of them received resveratrol, 11 – placebo. Dynamics of the blood analyte values (and HDRS-17 score) did not differ between resveratrol and placebo conditions (with the exception of BDNF levels, which increased slightly and unexpectedly with placebo). A positive correlation was found between the serum concentrations of SIRT1 and BDNF at each time point (significant – at weeks 0, 2, 6), as well as between their changes from week 0 to week 4 (p

AB - Background: We have previously reported the lack of efficacy of resveratrol (500 mg daily for 4 weeks) in the treatment of unipolar depression [1] as measured by the Hamilton Depression Rating Scale (HDRS-17). The second primary outcome measure in the study was a change in blood sirtuin-1 activity (clinicaltrials.gov # NCT03384329). The natural polyphenol flavonoid resveratrol is considered an activator of the antioxidant /cytoprotective enzyme SIRT1 [2] and is widely used in nutritional supplements [3]. Here we report the results of the effect of resveratrol on SIRT1 (activity, concentration, and expression in the blood) as well as on brain-derived neurotrophic factor (BDNF; an indicator of neuroplasticity and a potential biomarker of depression [4]). Methods: The recruited patients had to have major depressive disorder (MDD) or dysthymia, with melancholic features (DSM-5 criteria); HDRS-17 score at least 16; no antidepressant intake; absence of serious or unstable disease(s). Patients visited the clinic 5 times: on day -5 (selection), weeks 0 (inclusion), 2, 4 (during and after medication intake), and 6 (follow-up). The patients were administered to take randomly (1:1) resveratrol pill (Biotivia, USA) 500 mg daily in the morning or placebo pill, for 4 weeks (double-blind randomized placebo-controlled parallel-group design). Blood samples were taken at each post-selection visit between 12:00 and 13:00. The SIRT1 concentration (ng/ml) was assayed in serum by ELISA using the SIRT1 kit (MyBioSource, USA). Serum SIRT1 activity (units) was assayed by fluorometry of the enzyme kinetics using SIRT1 kit (Sigma-Aldrich, USA). SIRT1 gene expression (Ct value) was measured in whole blood (sampled in PaxGene tubes) by real-time PCR analysis. BDNF concentration in serum (pg/ml) was measured by xMAP technology on an analyser Luminex 200 using the Merck kit (Merck Millipore, USA). Each individual's serum samples were assayed in the same batch to avoid inter-assay variability. Results: Twenty-two patients completed the study (age ± SD 37.4 ± 9.7 years, range 23-59 years, 12 females), 11 of them received resveratrol, 11 – placebo. Dynamics of the blood analyte values (and HDRS-17 score) did not differ between resveratrol and placebo conditions (with the exception of BDNF levels, which increased slightly and unexpectedly with placebo). A positive correlation was found between the serum concentrations of SIRT1 and BDNF at each time point (significant – at weeks 0, 2, 6), as well as between their changes from week 0 to week 4 (p

UR - https://www.mendeley.com/catalogue/133d4bf3-4ab2-3c9f-acb9-478b7d435861/

U2 - 10.1016/j.euroneuro.2021.10.381

DO - 10.1016/j.euroneuro.2021.10.381

M3 - Meeting Abstract

VL - 53

SP - S295-S296

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

ER -