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1.
Extra-Virgin Olive Oil Improves Depression Symptoms Without Affecting Salivary Cortisol and Brain-Derived Neurotrophic Factor in Patients With Major Depression: A Double-Blind Randomized Controlled Trial.
Foshati, S, Ghanizadeh, A, Akhlaghi, M
Journal of the Academy of Nutrition and Dietetics. 2022;(2):284-297.e1
Abstract
BACKGROUND Many patients with depression are reluctant to take psychiatric medications. Hence, complementary therapies such as nutritional considerations could be advantageous. The antidepressant potential of olive oil has been proved in observational studies. OBJECTIVE The effect of extra-virgin olive oil (EVOO) on depression symptoms and cortisol and brain-derived neurotrophic factor (BDNF) levels in patients with depression was examined. DESIGN AND PARTICIPANTS This was a double-blind randomized controlled trial conducted on 73 patients suffering from major depressive disorder in Shiraz, Iran, in 2016. INTERVENTION The patients were randomly assigned to intervention (EVOO) and control (sunflower oil) groups and consumed 25 mL/d of the corresponding oil for 52 days. MAIN OUTCOME MEASURES Depression symptoms were assessed by Beck Depression Inventory-II (BDI-II) and 7-item Hamilton Depression Rating Scale (HAMD-7). Salivary cortisol levels were determined immediately after awakening and 30 minutes later. Cortisol awakening response and the area under the curve with respect to ground and increase were computed. Serum BDNF concentrations were also measured. STATISTICAL ANALYSES PERFORMED Statistical analysis was conducted based on intention-to-treat and per-protocol approaches. Within-group changes were examined with repeated measures (for BDI-II and HAMD-7) and with paired t test (for other variables). Between-group comparisons were performed with analysis of covariance after adjustment for confounding factors. RESULTS In intention-to-treat analysis, HAMD-7 score was the only variable with significant changes within and between groups, the latter as a greater decline in EVOO group (P = .001). BDI-II score did not show significant change in either group but the between-group comparison revealed a significant difference (P = .021). EVOO showed antidepressant effect in severely depressed patients (P = .017 for BDI-II and 0.008 for HAMD-7) but not in mild/moderate depression category. Serum BDNF concentrations, salivary cortisol levels at immediately after awakening (T0) and 30 minutes later, cortisol awakening response, the area under the curve with respect to ground and increase did not change within or between groups. Results of per-protocol analysis were not different. CONCLUSIONS The results of this study suggested beneficial effects of EVOO on depression symptoms in patients with severe depression but not in those with mild to moderate depression. The effects were significant from both statistical and clinical points of view.
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2.
The effects of wheat germ consumption on mental health and brain-derived neurotrophic factor in subjects with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial.
Mohammadi, H, Karimifar, M, Heidari, Z, Zare, M, Amani, R
Nutritional neuroscience. 2022;(1):46-53
Abstract
Objectives: Herbals, as bioactive foods, have been one of the most popular alternatives and complementary treatments in preventing and controlling type 2 diabetes mellitus (T2DM). The aim of the present trial was to examine the effects of wheat germ consumption on mental health and brain-derived neurotrophic factor (BDNF) among patients with T2DM.Methods: Eighty participants with T2DM were randomly allocated to receive 20 g wheat germ (n = 40) or placebo (n = 40) in a randomized double-blind clinical trial for 12 weeks. Depression, anxiety, stress scale-21 (DASS-21) questionnaire was used to assess the mental health of study participants. Serum BDNF was assessed at the baseline and end of intervention. Anthropometric indices were measured at the baseline, 6 and 12 weeks during the intervention.Results: A total of 75 subjects completed the trial. Compared with the placebo, wheat germ consumption led to a significant reduction in depression (P = .03) and stress (P = .04) scores. Moreover, a significant increase in serum BDNF concentrations was observed in the wheat germ group (P = .004), while there was no significant difference between the groups. Wheat germ intake had no significant effects on anthropometric indices and anxiety scores between the groups.Conclusion: Our findings showed that wheat germ consumption for 12 weeks could significantly reduce the stress and depression scores but had no significant effects on anxiety scale and anthropometric outcomes in patients with T2DM.
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3.
Superoxide Dismutase, BDNF, and Cognitive Improvement in Drug-Naive First-Episode Patients With Schizophrenia: A 12-Week Longitudinal Study.
Wu, Z, Liu, Q, Zhang, Y, Guan, X, Xiu, M, Zhang, X
The international journal of neuropsychopharmacology. 2022;(2):128-135
Abstract
OBJECTIVE Cognitive improvement after antipsychotic agents in patients with schizophrenia (SCZ) appears to involve redox regulation through neurotrophins such as brain derived neurotropic factor (BDNF). This study examined whether cognitive improvement was associated with the increase in superoxide dismutase (SOD) and whether higher levels of BDNF could have a permissive role in allowing SOD to improve cognition. METHODS We examined this hypothesis in 183 drug-naïve first-episode SCZ patients taking risperidone monotherapy for 12 weeks. We measured total copper-zinc SOD (CuZn-SOD), manganese SOD (Mn-SOD), and SOD activities and BDNF levels in these patients and compared their levels with 152 healthy controls. We assessed cognitive functioning and clinical symptoms at baseline and 12-week follow-up. RESULTS After treatment with risperidone, CuZn-SOD activity was significantly increased, and BDNF levels were slightly increased. Increased CuZn-SOD activity was associated with the cognitive effectiveness of risperidone monotherapy. The BDNF levels and SOD activities were correlated at baseline but not after 12-week treatment. Furthermore, baseline CuZn-SOD activity positively correlated with improvement on the delayed memory subscale of the Repeatable Battery for the Assessment of Neuropsychological Status only in the high BDNF subgroup. CONCLUSIONS Our longitudinal study suggests that risperidone can enhance SOD activity and that, in combination with higher baseline BDNF levels acting in a permissive role, can improve cognitive impairments in SCZ. Greater baseline CuZn-SOD activity also may have predictive value for cognitive improvement of delayed memory in SCZ patients receiving risperidone treatment.
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4.
Sedentary patterns are associated with BDNF in patients with type 2 diabetes mellitus.
Júdice, PB, Magalhães, JP, Hetherington-Rauth, M, Correia, IR, Sardinha, LB
European journal of applied physiology. 2021;(3):871-879
Abstract
PURPOSE Exercise is beneficial to type-2 diabetes-mellitus (T2DM), and there is evidence showing that one of those benefits include a higher expression of brain-derived neurotrophic factor (BDNF), which has been implicated in improving fat oxidation and cognitive development. The deleterious effect of prolonged sedentary time (ST) on BDNF levels has never been examined in patients with T2DM. Our goal was to analyse the associations for sedentary patterns [i.e. breaks in ST per sedentary hour (BST-ST) and bouts of sedentary time (BSB) of different length] with BDNF in patients with T2DM, independent of moderate-to-vigorous physical activity (MVPA) and cardiorespiratory fitness (CRF). METHODS Sample included 80 patients (38 women) with T2DM (58.3 ± 7.8 years). ST and MVPA were assessed by accelerometry (ActiGraph, GT3X + model), BDNF by blood collection and plasma quantification using commercial enzyme-linked immunosorbent assay kits, and CRF was determined using a Bruce protocol to exhaustion, on a motorized treadmill. RESULTS Positive associations for BST-ST (β = 0.155; p = 0.007) with BDNF, and negative associations for BSB longer than 15 min with BDNF were found (β = - 0.118; p = 0.049). Neither MVPA nor cardiorespiratory fitness eliminated the associations for BST-ST with BDNF, but MVPA eradicated the associations between BSB > 15 min and BDNF. CONCLUSIONS Our findings suggest that interrupting ST and especially avoiding longer sedentary periods (> 15 min) may be beneficial for BDNF plasma abundance that may influence metabolic and cognitive functioning of patients with T2DM, especially for the ones presenting lower MVPA levels. TRIAL REGISTRATION May 5, 2017, ClinicalTrials.govID:NCT03144505.
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5.
Interaction between dietary total antioxidant capacity and BDNF Val66Met polymorphism on lipid profiles and atherogenic indices among diabetic patients.
Abaj, F, Rafiee, M, Koohdani, F
Scientific reports. 2021;(1):19108
Abstract
Brain-derived neurotrophic factor (BDNF) belongs to the "neurotrophin" family of growth factors, and it has recently been associated to cardiovascular disease (CVD). We anticipated that BDNF Val66Met polymorphisms may alter CVD risk markers such as serum lipid profile differences, and interaction with total antioxidant capacity of diet (DTAC) could alter these clinical parameters. This cross-sectional study consisted of 667 diabetic patients (39.7% male and 60.3% female). DTAC was calculated by international databases. Biochemical markers including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), superoxide dismutase (SOD), C-reactive protein (CRP), total antioxidant capacity (TAC), pentraxin-3 (PTX3), isoprostaneF2α (PGF2α). interleukin 18 (IL18), leptin and ghrelin were measured by standard protocol. Atherogenic indices (AIP, AC, CR-I, CR-II) were calculated. Genotyping of the BDNF Val66Met polymorphisms was conducted by the real-time PCR-RFLP method. The gene-diet interactions were evaluated using a generalized linear mode (GLMs). Carriers of the Val/Met genotype who were in the higher median intake of FRAP had lower HDL (P:0.04) and higher TG (P:0.005), AIP (P:0.02) and AC (P:0.02) index compared to Val/Val genotypes with lower median intake. Moreover, diabetic patients with Val/Met genotype who consumed higher ORAC intake had increased odds for anthropometric indices (BMI (P:0.01) and WC (P:0.03)), lipid profiles (TG) (P:0.01), and atherogenic index (AIP) (P:0.02), also decreased odds for HDL (P:0.03) concentration compared to reference group whit lower ORAC intake. Individuals with Val/Met genotype who consumed higher TRAP intake had increased odds for WC (P:0.04), TC (P:0.001), TG (P < 0.001), AIP (P < 0.001) and AC (P < 0.001). Finally, Val/Met patients with a higher median intake of TEAC had higher TG (P:0.02), AIP (P:0.009) and AC (P:0.03) compared to the reference group whit lower TEAC intake. Our study showed that Val/Met genotype had also the highest lipid profile and atherogenic indices even in the highest adherence to DTAC. While it seems that the presence of the Val/Val wild-type and BDNF Met/Met homozygotes in diabetic patients with a high DTAC is a protective factor.
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6.
Screen time is independently associated with serum brain-derived neurotrophic factor (BDNF) in youth with obesity.
Goldfield, GS, Cameron, JD, Sigal, RJ, Kenny, GP, Holcik, M, Prud'homme, D, Guerin, E, Alberga, AS, D'Angiulli, A, Tremblay, MS, et al
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2021;(9):1083-1090
Abstract
Low levels of brain derived-neurotrophic factor (BDNF) and excessive screen exposure are risk factors for neurocognitive deficits and obesity in youth, but the relationship between screen time and BDNF remains unknown. This study examined whether duration and/or type of sedentary screen time behaviour (TV viewing, video games, recreational computer use) are associated with serum BDNF levels in youth with obesity. The sample consisted of 250 inactive, postpubertal adolescents with obesity (172 females/78 males, aged 15.5 ± 1.4 years) at the baseline assessment of the Healthy Eating, Aerobic, Resistance Training in Youth Study. After controlling for self-reported age, sex, race, parental education, puberty stage, physical activity, and diet, higher total screen exposure was significantly associated with lower serum BDNF levels (β = -0.21, p = 0.002). TV viewing was the only type of screen behaviour that was associated with BDNF levels (β = -0.22, p = 0.001). Higher exposure to traditional forms of screen time was independently associated with lower serum BDNF levels, and this association appears to be driven primarily by TV viewing. Future intervention research is needed to determine whether limiting screen time is an effective way to increase BDNF and associated health benefits in a high-risk population of youth with obesity. Trial Registration: ClinicalTrials.Gov NCT00195858. Novelty: This study is the first to show that recreational screen time is inversely associated with serum BDNF levels. The inverse association between screen time and BDNF is driven primarily by TV viewing, indicating the type of screen might matter.
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7.
Perisynaptic astrocytes as a potential target for novel antidepressant drugs.
Frizzo, ME, Ohno, Y
Journal of pharmacological sciences. 2021;(1):60-68
Abstract
Emerging evidence suggests that dysfunctions in glutamatergic signaling are associated with the pathophysiology of depression. Several molecules that act on glutamate binding sites, so-called glutamatergic modulators, are rapid-acting antidepressants that stimulate synaptogenesis. Their antidepressant response involves the elevation of both extracellular glutamate and brain-derived neurotrophic factor (BDNF) levels, as well as the postsynaptic activation of the mammalian target of rapamycin complex 1. The mechanisms involved in the antidepressant outcomes of glutamatergic modulators, including ketamine, suggest that astrocytes must be considered a cellular target for developing rapid-acting antidepressants. It is well known that extracellular glutamate levels and glutamate intrasynaptic time-coursing are maintained by perisynaptic astrocytes, where inwardly rectifying potassium channels 4.1 (Kir4.1 channels) regulate both potassium and glutamate uptake. In addition, ketamine reduces membrane expression of Kir4.1 channels, which raises extracellular potassium and glutamate levels, increasing postsynaptic neural activities. Furthermore, inhibition of Kir4.1 channels stimulates BDNF expression in astrocytes, which may enhance synaptic connectivity. In this review, we discuss glutamatergic modulators' actions in regulating extracellular glutamate and BDNF levels, and reinforce the importance of perisynaptic astrocytes for the development of novel antidepressant drugs.
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8.
The Influence of Val66Met Polymorphism in Brain-Derived Neurotrophic Factor on Stroke Recovery Outcome: A Systematic Review and Meta-analysis.
Liu, X, Fang, JC, Zhi, XY, Yan, QY, Zhu, H, Xie, J
Neurorehabilitation and neural repair. 2021;(6):550-560
Abstract
Background and purpose. A single nucleotide polymorphism at nucleotide 196 (G/A) in the human brain-derived neurotrophic factor (BDNF) gene produces an amino acid substitution (valine to methionine) at codon 66(Val66Met). It is unclear whether carriers of this substitution may have worse functional outcomes after stroke. We aimed to explore the distribution of Val66Met polymorphism and evaluate the effect of different genotypes on stroke functional recovery. Methods. Several databases were searched using the keywords BDNF or brain-derived neurotrophic factor, codon66, G196A, rs6265, or Val66Met, and stroke. Results. A total of 25 articles were relevant to estimate the distribution of alleles; 5 reports were applied in the meta-analysis to assess genetic differences on recovery outcomes. The genetic model analysis showed that the recessive model should be used; we combined data for AA versus GA+GG (GG-Val/Val, GA-Val/Met, AA-Met/Met). The results showed that stroke patients with AA might have worse recovery outcomes than those with GA+GG (odds ratio = 1.90; 95% CI: 1.17-3.10; P = .010; I2 = 69.2%). Overall, the A allele may be more common in Asian patients (48.6%; 95% CI: 45.8%-51.4%, I2 = 54.2%) than Caucasian patients (29.8%; 95% CI: 7.5%-52.1%; I2 = 99.1%). However, in Caucasian patients, the frequency of the A allele in Iranians (87.9%; 95% CI: 83.4%-92.3%) was quite higher than that in other Caucasians (18.7%; 95% CI: 16.6%-20.9%; I2 = 0.00%). Conclusion. Val66Met AA carriers may have worse rehabilitation outcomes than GA+GG carriers. Further studies are needed to determine the effect of Val66Met polymorphism on stroke recovery and to evaluate this relationship with ethnicity, sex, age, stroke type, observe duration, stroke severity, injury location, and therapies.
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9.
A reconciling hypothesis centred on brain-derived neurotrophic factor to explain neuropsychiatric manifestations in rheumatoid arthritis.
Pedard, M, Quirié, A, Tessier, A, Garnier, P, Totoson, P, Demougeot, C, Marie, C
Rheumatology (Oxford, England). 2021;(4):1608-1619
Abstract
Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease characterized by synovitis leading to joint destruction, pain and disability. Despite efficient antirheumatic drugs, neuropsychiatric troubles including depression and cognitive dysfunction are common in RA but the underlying mechanisms are unclear. However, converging evidence strongly suggests that deficit in brain-derived neurotrophic factor (BDNF) signalling contributes to impaired cognition and depression. Therefore, this review summarizes the current knowledge on BDNF in RA, proposes possible mechanisms linking RA and brain BDNF deficiency including neuroinflammation, cerebral endothelial dysfunction and sedentary behaviour, and discusses neuromuscular electrical stimulation as an attractive therapeutic option.
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10.
The role of physical exercise in modulating peripheral inflammatory and neurotrophic biomarkers in older adults: A systematic review and meta-analysis.
Titus, J, Bray, NW, Kamkar, N, Camicioli, R, Nagamatsu, LS, Speechley, M, Montero-Odasso, M
Mechanisms of ageing and development. 2021;:111431
Abstract
BACKGROUND Physiological cascades of neurotrophic factors and inflammatory cytokines may mediate the exercise-induced amelioration of cognition in older adults. However, there is limited understanding on how different exercise modalities improving cognition alter biomarkers. Our aim was to evaluate the effects of different exercise modalities on blood biomarker concentrations in cognitive clinical trials of older adults. METHODS A systematic review (SR) and meta-analysis (MA) were performed using the databases PubMed, EMBASE, and SCOPUS. After exclusions, 17 trials with 18 distinct exercise interventions were included. RESULTS Aerobic training increased (n = 2) or did not significantly change BDNF (n = 5), and resistance training increased (n = 2) or did not significantly change (n = 2) IGF-1. Multimodal training significantly increased (n = 1) or did not change (n = 3) BDNF. Interventions that recruited sex-specific cohorts showed an advantage in males for blood marker concentrations and cognitive performance outcomes (n = 3) compared to females (n = 3). Only one of three interventions decreased concentrations of CRP. Eight studies examining BDNF changes were suited for MA and showed that higher BDNF concentrations were reached post intervention, although not reaching statistical significance (p = .26, I2 = 44 %). DISCUSSION Our results suggest that exercise has potential to ameliorate cognitive decline in older adults with divergent, modality-specific, neurotrophic mechanisms.