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This longitudinal study explored the intricate relationships between serum Brain-Derived Neurotrophic Factor (sBDNF) levels, exposure to childhood adversities, and the subsequent development of Post-Traumatic Stress Disorder (PTSD), distinguishing between earlier- and delayed-onset forms over a two-year follow-up period in individuals sustaining physical injuries. We recruited patients presenting with moderate to severe physical injuries at a trauma center, conducting baseline assessments of sBDNF levels and childhood adversities through the Adverse Childhood Experiences (ACE) questionnaire. Additionally, detailed socio-demographic and clinical data were compiled. The Clinician-Administered PTSD Scale for DSM-5 was employed to diagnose PTSD at 3, 6, 12, and 24 months post-injury. Binary and multinomial logistic regression analyses were applied to elucidate the interactions between sBDNF levels, childhood adversities, and PTSD onset patterns. Among 895 participants, PTSD was diagnosed in 107 individuals (11.9 %), with 76 (8.4 %) exhibiting symptoms indicative of earlier-onset PTSD and 31 (3.5 %) demonstrating delayed-onset PTSD. Significantly, lower sBDNF levels were associated with a higher risk of earlier-onset PTSD specifically in the context of childhood adversities. This association was not observed in individuals without childhood adversities or in those with delayed-onset PTSD. The findings suggest a complex and critical interplay between neurobiological factors, specifically sBDNF levels, and early life adversities in influencing the timing of PTSD onset, potentially deepening the understanding of PTSD etiology., Competing Interests: Declaration of Competing Interest No potential conflict of interest relevant to this article was reported., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS) is perceived as an emerging environmental endocrine disruptor, which have been linked to children neurodevelopment. However, the potential mechanisms are not clear. Brain-derived neurotrophic factor (BDNF) is a vital protein in neurodevelopment, and the associations between PFAS exposure and BDNF require exploration., Objective: We aimed to explore the relationships between PFAS exposure and the levels of BDNF in cord serum., Methods: A total of 1,189 mother-infant dyads from the Sheyang Mini Birth Cohort Study (SMBCS) were enrolled. The levels of 12 PFAS and BDNF were measured in cord serum. We utilized generalized linear models (GLMs), quantile-based g-computation (QGC) models, and Bayesian Kernel Machine Regression (BKMR) models to explore the relationships between single and mixed PFAS exposure and BDNF concentration. Additionally, the potential sex differences were explored by sex-stratified analysis., Results: Median concentrations of the included 10 PFAS ranged from 0.04 to 3.97 μg/L. In the single chemical models, four PFAS congeners, namely perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), were negatively associated with BDNF levels in cord serum among females only (β: -0.116 to -0.062, p < 0.05). In the BKMR models of total mother-infant dyads and female fetuses, the significant negative relationships between PFAS mixtures and BDNF were observed, and PFUnDA was identified as an important contributor (Posterior inclusion probability, PIP = 0.8584 for the total subjects; PIP = 0.8488 for the females). PFOS was another important driver based on the mixture approaches., Conclusions: We found that PFNA, PFOS, PFDA, and PFUnDA were associated with decreased BDNF concentration in the females, although the causal inference might be limited. PFAS mixtures were also negatively linked with BDNF levels in the total mother-infant pairs and female fetuses. The adverse effect of PFAS exposure on fetal BDNF levels might be sex-specific., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Zhijun Zhou reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder and a leading cause of disability worldwide. Brain-derived neurotrophic factor (BDNF), a signaling protein responsible for promoting neuroplasticity, is highly expressed in the central nervous system but can also be found in the blood. Since impaired brain plasticity is considered a cornerstone in the pathophysiology of MDD, measurement of BDNF in blood has been proposed as a potential biomarker in MDD. The aim of our study is to systematically review the literature for the effects of antidepressant treatments on blood BDNF levels in MDD and the suitability of blood BDNF as a biomarker for depression severity and antidepressant response. We searched Pubmed® and Cochrane library up to March 2024 in a systematic manner using Medical Subject Headings (MeSH). The search resulted in a total of 42 papers, of which 30 were included in this systematic review. Generally, we found that patients with untreated MDD have a lower blood BDNF level than healthy controls. Antidepressant treatments increase blood BDNF levels, and more evidently after pharmacological than non-pharmacological treatment. Neither baseline nor change in the blood BDNF level correlates with depression severity or treatment outcome, which undermines its use as a biomarker in MDD. Our review also highlights the importance of considering factors influencing the accuracy and reproducibility of BDNF measurements. We summarize considerations to help obtain more robust blood BDNF values and compile a list of recommendations to help streamline assessment of blood BDNF levels in future studies., Competing Interests: Declaration of competing interest EC is a co-founder and a board member of Kasvu Therapeutics and has received speaker fees from Janssen-Cilag. GMK has within the last 3 years received speaker fees from H. Lundbeck, Abbvie and Angelini and is a consultant for several pharmaceutical companies unrelated to this paper. LVK has within the last 3 years received speaker fees from Lundbeck and Teva. All other authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Study Objective: To investigate whether a single dosage of esketamine injection in the anesthesia period could improve postoperative negative emotions and early cognitive function in patients undergoing non-cardiac thoracic surgery., Design: A prospective single center double blinded randomized placebo-controlled trial., Setting: Perioperative period; operating room, post anesthesia care unit and hospital ward., Patients: 129 adult patients that underwent elective non-cardiac thoracic surgery under general anesthesia., Interventions: During the operation, pharmacologic prevention of postoperative negative emotion and early cognitive disorder with 0.2 mg/kg (Low esketamine group) and 0.5 mg/kg esketamine (High esketamine group) vs. placebo., Measurements: Emotion and early cognitive performance were assessed on the day before surgery (POD-1), postoperative day 1 (POD1) and day 3 (POD3) using HADS-A, HADS-D, Pain Visual Analogue Scale (VAS), Confusion Assessment Method (CAM), Mini-Mental State Examination (MMSE), and serum biomarkers (S100β, BDNF, IL-6, acetylcholine, and norepinephrine)., Main Results: The high esketamine group showed significantly lower HADS-A and HADS-D scores than control group on POD1 and POD3. No significant differences were observed between the low esketamine group and the control group. The esketamine-treated groups showed lower pain VAS scores than the control group at 2 h and on the first day after operation. There were no significant differences among the three groups in CAM and MMSE scores. However, the high esketamine group had lower S100β and IL-6 levels, and higher BDNF levels postoperatively, while serum acetylcholine and norepinephrine were not significantly different., Conclusions: A single intraoperative injection of 0.5 mg/kg esketamine can alleviate postoperative anxiety, depression, and pain to some extent. Although cognitive function behavioral evaluation did not show obvious benefits, it can also reduce the production of pro-inflammatory and brain injury-related factors while promoting the generation of brain-derived neurotrophic factor. Registration Trial registry: http://www.chictr.org.cn/; Identifier: ChiCTR2100047067., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: There is a lack of evidence on dietary intake of methyl donor nutrients with metabolic health status and related biomarkers. Thus, this study aimed to assess the relation between methyl donor nutrients intake and metabolic health status with regarding the interactive roles of brain-derived neurotrophic factor (BDNF) and adropin in Iranian adults., Methods: This cross-sectional survey was conducted among 527 Iranian adults (45.7% female) selected by multistage cluster random-sampling method. A validated food frequency questionnaire was used to evaluate participants' dietary intake. Metabolic unhealthy status was defined by Wildman criteria as having ≥ 2 of hyperglycemia, hypertriglyceridemia, hypo-HDL-cholesterolemia, hypertension, chronic inflammation, and insulin resistance. Concentrations of metabolic parameters, BDNF and adropin were determined using fasting blood samples., Results: An inverse association was found between methyl donor nutrients intake and metabolically unhealthy status in multivariable-adjusted model (OR T3 vs. T1  = 0.30; 95%CI: 0.12-0.75). This association was especially significant among overweight/obese adults and was stronger in women. Additionally, consumption of vitamin B6 and choline was separately related to reduced odds of metabolically unhealthy status. Methyl donor intake was not significantly related to low BDNF (OR T3 vs. T1  = 0.93; 95%CI: 0.60-1.44) and adropin (OR T3 vs. T1  = 0.71; 95%CI: 0.44-1.15). However, the interaction between high methyl donor nutrients intake and high BDNF was related to lower odds of metabolically unhealthy status in multivariable-adjusted model (OR MDNS∗BDNF  = 0.27; 95%CI: 0.11-0.67)., Conclusion: Higher intake of methyl donor nutrients, alone and in interaction with BDNF levels, was associated with decreased odds of metabolically unhealthy status in Iranian adults., Competing Interests: Conflict of interest None., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Multiple sclerosis (MS) is a chronic demyelinating autoimmune neurodegenerative disorder for which no specific blood biomarker is available. MicroRNAs (miRNAs) have been investigated for their diagnostic potential in MS. However, MS-associated miRNAs are rarely replicated in different MS populations, thus impeding their use in clinical testing. Here, we evaluated the fold expression of seven reported MS miRNAs associated with MS incidence and clinical characteristics in 76 MS patients and 75 healthy control plasma samples. We found miR-23a-3p to be upregulated in relapsing-remitting MS (RRMS), while miR-326 was downregulated. MiR-150-5p and -320a-3p were significantly downregulated in secondary progressive MS (SPMS) patients compared to RRMS. High disability was associated with low miR-320a-3p, whereas low BDNF levels were associated with upregulation of miR-150-5p and downregulation of miR-326 expression in the total cohort. MiR-23a-3p and miR-326 showed significant diagnostic sensitivity, specificity, and accuracy for RRMS diagnosis. In addition, miR-150-5p and miR-320a-3p had comparable significant diagnostic test performance metrics distinguishing SPMS from RRMS. Therefore, there is potential for including miR-23a-3p and miR-326 in an RRMS diagnostic miRNA panel. Moreover, we have shown that miR-150-5p and miR-320a-3p could be novel RRMS conversion to SPMS biomarkers. The use of these miRNAs in MS diagnosis and prognosis warrants further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Early neurological deterioration (END) is a common complication of cerebral infarction and a significant contributor to poor prognosis. Our study aimed to investigate the predictive value of interleukin-9 (IL-9) and interleukin-11 (IL-11) in relation to the occurrence of END in patients with cerebral infarction., Materials and Methods: 102 patients with cerebral infarction and 64 healthy controls were collected. Patients were categorized into two groups based on the development of END following admission: the END group (n = 44) and the non-END group (n = 58). Enzyme-linked immunosorbent assay was used to determine the serum levels of IL-9, IL-11, and BDNF., Results: Serum IL-9 was higher and IL-11 lower in the END group than those in the non-END group (P < 0.01). IL-9 correlated positively with NIHSS score (r = 0.627) and infarction volume (r = 0.686), while IL-11 correlated negatively (r = -0.613, -0.679, respectively). Logistic regression identified age, NIHSS score, and IL-9 as risk factors (P < 0.01), and IL-11 as protective (P < 0.01). Combined IL-9 and IL-11 had an ROC curve area of 0.849. BDNF correlated negatively with IL-9 (r = -0.703) and positively with IL-11 (r = 0.711)., Conclusion: Serum IL-9 and IL-11 levels can predict the occurrence of END in patient with cerebral infarction and are correlated with serum BDNF levels., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Millions of Americans experience traumatic orthopaedic injuries (TOIs) annually. Post-injury symptoms of acute stress disorder (ASD), anxiety, depression, pain, and sleep disturbance are common. Symptoms often present in clusters. Symptom cluster profiles phenotypically characterize TOI survivors' experiences with clustered symptoms. Expression of brain-derived neurotrophic factor (BDNF) may contribute to the biological underpinnings of symptom cluster profile membership., Methods: We recruited hospitalized TOI survivors within 72 hours of injury. We measured symptoms of ASD with the Acute Stress Disorder Scale and symptoms of anxiety, depression, pain, and sleep disturbance with Patient-Reported Outcomes Measurement Information System (PROMIS) short forms. We measured serum BDNF concentrations with enzyme-linked immunosorbent assay (ELISA) and identified rs6265 genotypes with TaqMan real-time PCR. We performed latent profile analysis to identify the symptom cluster profiles. We identified the variables associated with symptom cluster profile membership with unadjusted and adjusted multinomial logistic regression., Results: We identified 4 symptom cluster profiles characterized by symptom severity that we labelled Physical Symptoms Only, and Mild, Moderate, and Severe Psychological Distress. Age, self-identified Black race, resilience, and serum BDNF concentrations were associated with lower odds, and female sex with higher odds, of being in the Psychological Distress clusters. Clinical characteristics and rs6265 genotypes were not associated with symptom cluster profile membership., Conclusion: TOI survivors experience distinct symptom cluster profiles. Sociodemographic characteristics and serum BDNF concentrations, not clinical characteristics, were associated with symptom cluster profile membership. These findings support comprehensive symptom screening and treatment for all TOI survivors and further evaluating BDNF as a biomarker of post-injury symptom burden., Competing Interests: Declaration of Competing Interest The following authors declare the following financial and/or personal relationships that could inappropriately bias their work: Stephen Breazeale: Dr. Breazeale's doctoral studies were funded in part by the Robert Wood Johnson Foundation Future of Nursing Scholars Program. This publication was made possible by CTSA Grant Number TL1 TR001864 from the National Center for Advancing Translational Science (NCATS), components of the National Institutes of Health (NIH), and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH. This publication was cosponsored by the Rockefeller University Heilbrunn Family Center for Research Nursing through the generosity of the Heilbrunn Family and the National Center for Advancing Translational Sciences, National Institutes of Health, through Rockefeller University, Grant # UL1 TR001866. Research reported in this publication was supported by the National Institute of Nursing Research of the National Institutes of Health under Award Number F31NR018996. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; Samantha Conley: No conflicts to disclose; Sangchoon Jeon: No conflicts to disclose; Susan G. Dorsey: No conflicts to disclose; Joan Kearney: No conflicts to disclose; Brad Yoo: No conflicts to disclose; Nancy S. Redeker: No conflicts to disclose., (Copyright © 2022. Published by Elsevier Ltd.)

Neurotrophins have been proposed to be involved in biological mechanisms which might underlie different clinical outcomes in schizophrenia. The aims of the present study were to examine the BDNF/NGF plasma levels in a cohort of first-episode schizophrenia (FES) patients in remission as potential biological predictors of relapse; to study the associations between these neurotrophins and the symptomatology severity through different stages after a FES in two independent cohorts. 2EPs-Cohort: 69 first-episode in clinical remission were included. BDNF/NGF plasma levels and symptom severity were measured at enrollment and at 3-year or at the time of the second episode/relapse. FLAMM-PEPs-Cohort: 65 first-episodes were also included. BDNF/NGF and symptom severity were obtained at enrollment and 2-year follow-up. Symptomatology was assessed with the Marder-PANSS-Factor scores. Plasma neurotrophins did not differ significantly over time and neither BDNF/NGF were predictors of relapse. Besides, in remission stages, baseline BDNF levels showed significant correlations with both positive and negative symptoms (p<0.05); NGF, with negative symptomatology (p<0.01). Similarly, in the FLAMM-PEPs-Cohort, baseline BDNF/NGF levels showed significant correlations with negative symptoms (and not positive symptomatology) at follow-up (p<0.05). In both cohorts, lower levels correlated with higher symptom severity. Findings did not support a role for BDNF/NGF plasma levels as biomarkers of relapse in FES patients. Nevertheless, baseline BDNF/NGF may lead to be considered potentially useful biomarkers of long-term severity in schizophrenia and of the underlying illness traits, specially of negative symptomatology severity. More longitudinal studies in FES samples and adding a control group are warranted to replicate these findings., Competing Interests: Conflict of Interest Dr. Bernardo has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda. Pilar A Sáiz, has been a consultant to and/or has received honoraria or grants from Adamed, CIBERSAM, European Comission, Government of the Principality of Asturias (PCTI-2018–2022 IDI/2018/235), Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Plan Nacional sobre Drogas and Servier. The rest of authors have declared that there are no conflicts of interest in relation to the subject of this study., (Copyright © 2022. Published by Elsevier B.V.)

Background: Few studies have compared serum BDNF and glycolipid profiles in patients with deficit schizophrenia (DS) and non-deficit schizophrenia (NDS). We aimed to compare BDNF and glycolipid profiles between DS and NDS patients and healthy controls, and to investigate the relationship between BDNF, glycolipid profiles in DS and NDS patients., Methods: A total of 591 patients with chronic schizophrenia (SZ) and 238 healthy controls participated in this study. According to Proxy for the Deficit Syndrome Scale, SZ patients were divided into DS (n = 158) and NDS (n = 273) patients. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Serum BDNF levels were measured using enzyme-linked immunosorbent assay (ELISA)., Results: BDNF levels were significantly lower in SZ patients than those in healthy controls (7.81 ± 2.98 ng/ml vs. 11.96 ± 2.29 ng/ml, P < 0.01). Furthermore, BDNF levels were lower in DS group than those in NDS group (P = 0.007, OR = 0.846, 95% CI = 0.750-0.955). Lower triglyceride levels were also an independent predictor for DS patients (P = 0.007, OR = 0.846, 95% CI = 0.750-0.955). Serum BDNF levels were negatively associated with the severity of deficit syndrome in SZ patients (β = -1.151, t = -2.559, P = 0.011). In DS group, triglycerides were associated with PANSS negative subscore (β = -0.262, t = -2.994, P = 0.003) and depressive factor subscore (β = 0.282, t = 2.146, P = 0.035)., Conclusion: Serum BDNF and triglycerides may be informative biomarkers of DS in SZ patients. The differences in glycolipid metabolism patterns between DS and NDS patients indicate that deficit syndrome is an independent endophenotype of SZ patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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 (T 0 ) 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., (Copyright © 2022 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Brain-derived neurotrophic factor (BNDF) plays a role in synapse integrity. We investigated in 398 cognitively normal adults (60±8years, 41% female, MMSE=28±1) the joint association of the Val66Met polymorphism of the BDNF gene (Met+/-) and plasma BDNF levels and abnormal cerebrospinal fluid (CSF) amyloid-beta status (A+/-) with cognitive decline and dementia risk. Age-, sex- and education-adjusted linear mixed models showed that compared to Met-A-, Met+A+ showed steeper decline on tests of global cognition, memory, language, attention and executive functioning, while Met-A+ showed steeper decline on a smaller number of tests. There were no associations between Met+A- and cognitive decline. Cox models showed that compared to Met-A-, Met+A+ participants were at increased risk of dementia (HR=8.8, 95%CI: 2.8-27.9), as were Met-A+ participants (HR=6.5, 95%CI: 2.2-19.5). Lower plasma BDNF was associated with an increased risk of progression to dementia in the A+ participants. Our results imply that Met-carriage on top of amyloid-beta pathology might increase rate of cognitive decline to dementia., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Depression is the world's predominant mental health problem and a leading cause of disability. Neuropharmacological research has not yet advanced treatments to sufficiently meet clinical need, largely due to the failure of animal models to predict clinical efficacy. The forced swim test (FST) has been extensively used in the field of antidepressant research but has been under scrutiny due to its perceived severity to animals. Any use of animals in experiments and testing must have a scientific or regulatory purpose and researchers need to ensure that there is no scientifically valid alternative. However, regulatory requirements have been incorrectly cited as a reason to support the use of the FST. More research is required on tests that do not involve stressing animals as replacements for the FST. Non-behavioural neurochemical measures might provide a means to advance neuropharmacological developments while reducing animal suffering. For example, brain-derived neurotrophic factor (BDNF) may be promising., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Schizophrenia is a serious long-term disorder in which the metabolic complications and abnormalities of the brain-derived neurotrophic factor (BDNF) can be found. In this study, we conducted a systematic review of the relationship between BDNF, metabolic syndrome (MetS) and its components in schizophrenic patients., Methods: Data were collected mainly from PubMed, Google Scholar, Scopus, and ProQuest databases. The keywords related to the BDNF, MetS, schizophrenia were searched. Two reviewers independently screened 1061 abstracts. And eventually, a total of 7 studies (6 observational and 1 interventional) was included in the systematic reviews., Results: Four of the 7 study ascertained statistically significant inverse relationship between serum BDNF levels and MetS in schizophrenic patients. While in the other two studies, there was no inverse relationship. In the last selected study, the researchers found a weak association between the Val66Met polymorphism in BDNF Gene and clozapine-induced MetS., Conclusion: Although this relationship could not be determined but BDNF levels appear to be reduced in schizophrenic patients with MetS and factors such as sex and antipsychotic class differentiation, sampling and methodology and episodes of illness could play a role in the results and outcomes., (Copyright © 2021. Published by Elsevier Ltd.)

Serum BDNF concentrations in 2053 participants of the Berlin Aging Study II (BASE-II; 1572 individuals from the older age group [60-85 years], 481 individuals from the younger-age reference group [22-37 years]) were studied. There was no effect of age, sex, body mass index, self-reported depression, or BDNF Val66Met variant on serum BDNF concentrations. Multiple linear regression analysis failed to detect significant relationships of Digit Symbol Substitution Test score and Consortium to Establish a Registry for Alzheimer's Disease memory score to BDNF levels. However, we detected a positive correlation between platelet counts and BDNF levels (r = 0.303, p < 0.001). Our findings do not support an effect of aging, self-reported depression, or the Val66Met variant on serum BDNF concentrations. The role of thrombocytes in the biology of serum BDNF merits further study., Competing Interests: Disclosure statement The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Diabetes during pregnancy is associated with an increased risk of foetal and neonatal complications and long-term complications in the offspring. Brain-derived neurotrophic factor (BDNF), a neurotrophin that has a crucial role in neurogenesis modulation and neural pathway maturation during neurodevelopment, may have a role in protecting neurons against injury and diseases by modulating glucose metabolism. The aim of this study was to investigate the possible relationship between the serum BDNF levels of infants of mothers with gestational diabetes (IMGD) and neurodevelopmental outcomes of the children after birth., Methods: A total of 24 candidates, including 8 IMGD and 16 healthy infants, were recruited for the study. Medical records were reviewed. Serum BDNF levels of the study participants were collected at birth and at 6 and 12 months of age. Developmental outcomes of each candidate were assessed using the Bayley Scales of Infant Development III (BSID III) at 6 and 12 months of corrected age., Results: Compared to non-IMGD, IMGD had greater mean body weight (p = 0.04) and height (p < 0.01) at age 12 months. The language composite score was significantly lower in IMGD at 12 months of age (p = 0.038). The BDNF content was significantly higher in the non-IMGD than in the IMGD group at 12 months of age (p = 0.013)., Conclusion: In this study, we demonstrated that infants of mothers with gestational diabetes do worse in language development and have lower BDNF levels at 12 months of age. There may be a close correlation between language outcomes and serum BDNF levels at 12 months of age. A follow-up study on future developmental status is warranted., Competing Interests: Declaration of competing interest The authors have declared that they have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor highly expressed in coronary plaques, particularly in macrophages, and in activated platelets. Thus, a possible role in the pathogenesis of acute coronary syndrome (ACS) has been suggested. We evaluated systemic BDNF levels according to the different clinical presentations of ACS. Moreover, we assessed the relationship between BDNF levels and the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) and healed plaques along the culprit vessel. We enrolled consecutive patients presenting with ST-elevation myocardial infarction (STEMI) or non-ST-elevation (NSTE)-ACS. Serum BDNF levels were assessed by enzyme-linked immunosorbent assay. Plaque characteristics of the culprit vessel were assessed by OCT. Among 126 ACS patients (median age 68.00, interquartile range [IQR] 59.75-75.25 years, male 74.6%, 71 (56.3%) were NSTE-ACS and 55 (43.7%) were STEMI. BDNF levels were higher in STEMI patients compared to NSTE-ACS. OCT assessment was performed in 53 (42.1%) patients. Patients with MØI (n = 27) had higher BDNF levels compared to patients without MØI. Furthermore, patients with healed plaques (n = 13) had lower BDNF levels than patients without healed plaques. At multivariate regression analysis BDNF levels independently predicted the presence of MØI (odds ratio [OR] = 2.856; 95% confidence interval [CI] [1.151-7.090], P = 0.024) and the absence of healed plaques (OR = 0.438, 95% CI [0.185-0.992], P= 0.050). Among ACS patients, BDNF levels were higher in patients with STEMI. Moreover, BDNF levels were independently associated with MØI and with the absence of healed plaques along the culprit vessel, suggesting a possible role of BDNF in promoting plaque inflammation, destabilization and occlusive thrombosis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-naïve patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N = 62), or not (weight stable cancer, WSC, N = 32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p = 0.047), higher FABP3 plasma content (p = 0.0301) and higher tumor tissue expression of FABP3 (p = 0.0182), IL-15 (p = 0.007) and irisin (p = 0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p = 0.0149, p = 0.0455 and p = 0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p = 0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may contribute to the systemic scenario), and put forward new perspectives on cachexia treatment targeting myokines and associated receptors and pathways., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Mercury (Hg), a ubiquitous heavy metal, could affect the neurodevelopment of the children, however, these associations are still equivocal. Brain derived neurotrophic factor (BDNF) plays an essential role in the central nervous system development in children. This study aimed to investigate the effects of low-level mercury exposure on serum BDNF levels and the influence of sex and dietary intake on these relationships in children., Methods: In this cross-sectional study, a total of 541 pre-school children were recruited, the blood mercury concentrations and serum BDNF levels were measured. The background information on demographic characteristics and dietary habits of the children was collected through questionnaires. Multivariable linear models after adjustment for potential confounders were used to evaluate the associations between mercury exposure and levels of BDNF in children., Results: The GMs of blood mercury concentrations and serum BDNF levels were 1.06 μg/L, 20.4 ng/mL, respectively. A significant positive association between blood mercury concentrations and serum BDNF levels was found. After stratification by sex, the blood mercury concentrations in children were positive associated with serum BDNF levels in girls but not in boys. However, these associations were attenuated when we further adjusted the children's dietary intake variables., Conclusions: Our findings suggest that low-levels of mercury exposure may have sex-specific effects on BDNF levels in young children and that dietary intake may be potential confounders in these relationships. However, further studies are warranted to investigate the role of BDNF in the effects of mercury on neurodevelopment., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Emerging hypotheses in the pathophysiology of major depressive disorder (MDD) indicate the role of neurotrophic factors and inflammation. This study assessed the association between therapeutic response of bupropion and serum brain-derived neurotrophic factor (BDNF) and tumour necrosis factor-α (TNF-α) levels in patients with MDD., Methods: Thirty patients (aged 18 to 60 years) with MDD diagnosed by DSM-5 criteria, with Hamilton Depression Rating scale (HAM-D) score ≥ 20 were included in the study. Patients were given bupropion sustained release (SR) in the doses of 150 mg once daily. All patients were followed up for 12 weeks., Results: HAM-D score at the start of the treatment was 25.57 ± 1.85 which significantly reduced to 10.8 ± 4.24 at 12 weeks of treatment. The serum BDNF level increased significantly (p < 0.05) from 2.42 ± 0.19 ng/ml to 2.97 ± 0.10 ng/ml and the levels of serum TNF-α reduced significantly (p < 0.05) from 4.45 ± 0.95 pg/ml to 2.11 ± 0.84 pg/ml at 12 weeks of treatment, in responders to treatment., Conclusion: The results of our study suggest that bupropion SR monotherapy is effective and well tolerated in MDD patients with moderate to severe depression, and its therapeutic efficacy is accompanied by an increase in serum BDNF levels and a decrease in serum TNF-α levels., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Abnormalities in brain development and plasticity have been associated with the pathophysiology of schizophrenia. The role of brain-derived neurotrophic factor (BDNF) in schizophrenia is the recent area of interest because it regulates neurogenesis. The current study aimed to assess and compare serum BDNF levels between first-episode schizophrenia patients and healthy controls, and evaluate its correlation with the socio-demographic and clinical variables., Methodology: It was a cross-sectional comparative study for the assessment of serum BDNF levels between patients with first-episode schizophrenia (N=50) and healthy controls (N-50) conducted in the Department of Psychiatry at a tertiary care public hospital attached to a medical school in North India. Participants were assessed for the socio-demographic parameters, nicotine dependence, and clinical details using structured scales. Serum BDNF level estimated using the sandwich ELISA technique. The comparison between the groups was done by using a Student t-test or chi-square test. Spearman correlation was performed between mean BDNF scores and demographic or illness variables in both first-episode schizophrenia and healthy control groups., Results: There was a significantly lower mean score of total serum BDNF levels in first-episode schizophrenia patients as compared to controls (8.44 ± 1.54 vs 10.44 ± 2.04; t = 5.52, p < 0.001; 95% CI = 1.28-2.71). The total FTND scores for smokeless tobacco use were negatively correlated to BDNF levels among healthy controls (r=-0.30, p=0.03) as well as in the first-episode schizophrenia group (r=-0.32, p= 0.04). None of the other illness-related variables were correlated to serum BDNF values in the first episode schizophrenia group., Conclusion: Individuals with first-episode schizophrenia have lower serum BDNF levels than healthy controls. The illness-related factors such as duration of untreated psychosis or psychopathology were not correlated with BDNF levels. Thus abnormal signaling of BDNF can lead to abnormal brain functioning which can make an individual more susceptible to schizophrenia., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The neurotrophin hypothesis indicates that neurotrophic factors are important for the pathophysiology of major depressive disorder (MDD), with alterations in peripheral neurotrophin levels having potential clinical application for MDD. The present meta-analysis aimed to investigate the diagnostic value for MDD of peripheral neurotrophin levels in cross-sectional studies and the association between peripheral neurotrophin levels and the response to antidepressant treatment in longitudinal studies. Published studies in the PubMed and Web of Science databases were systematically searched up to February 2020. The search terms included depressive disorder, neurotrophic factor, serum/plasma and their synonyms. Human studies reporting on BDNF, GDNF, IGF-2, VEGF, NGF, FGF-2, and S100B levels in MDD patients were included. Data comparing MDD patients and healthy controls, and/or between responders and non-responders before and after antidepressant treatment were extracted. A random effects model was used to calculate standardized mean differences. A total of 177 original studies were identified, including 139 cross-sectional and 38 longitudinal studies. Significantly reduced BDNF and NGF levels and significantly elevated IGF-1, VEGF, and S100B levels were reported in MDD patients compared with healthy controls, while GDNF and FGF-2 levels were not significantly different. Furthermore, compared with non-responders, S100B levels at baseline and BDNF levels following treatment were significantly elevated in responders. In addition, there was a significantly elevated level of VEGF after treatment in responders only. In conclusions, alterations in peripheral neurotrophins levels were strongly associated with the biology and the treatment response of MDD. Further investigations are required to examine potential sources of heterogeneity., Competing Interests: Conflict of Interest The authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

Psychiatric disorders and childhood trauma are highly prevalent in female inmates. Brain-derived neurotrophic factor (BDNF) plays a number of roles in neuronal survival, structure, and function. Data in the literature suggest that it is a neurobiological substrate that moderates the impact of childhood adversities on the late expression of psychiatric disorders. The aim of this study was to determine whether five childhood trauma subtypes-physical abuse, sexual abuse, emotional abuse, physical neglect, and emotional neglect-are associated with adult psychiatric disorders, BDNF levels, and criminality among incarcerated women. This was a cross-sectional study involving a consecutive sample of 110 women, divided into three groups of women (forensic - mentally ill who committed crimes, clinical psychiatric inpatients and healthy controls). The Childhood Trauma Questionnaire and the Mini-International Neuropsychiatric Interview-Plus were applied in the whole sample, and BDNF levels were measured in a sub-sample of 54 women. The rates of mental illness and childhood trauma were high in the forensic group. Emotional abuse was higher in the clinical and forensic groups than in the healthy control group. Lower BDNF levels were associated with emotional abuse in the forensic group as well as with sexual abuse in the healthy control group. After multinomial logistic regression, lower levels of BDNF, higher levels of emotional abuse and the presence of familial offense were considered factors related to clinical psychiatric group. The results of this study underscore the idea that BDNF may be an important factor related to the development of diseases and criminality in women who are victims of childhood trauma, becoming a possible biological marker., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Exercise-induced changes in the neurotrophic factors and the physical function are essential for the rehabilitation of the multiple sclerosis (MS) persons. The aim of this study was investigating of effectiveness of the combined functional training (CFT) on brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and their association with health-related fitness in the MS women., Design: Twenty women with relapsing-remitting MS randomly assigned to CFT and control (CON) groups. The CFT consisted of 8 weeks (3 days per week) rhythmic aerobic exercise, TRX suspension training, elastic band training, and bodyweight training. BDNF, IGF-1, and health-related fitness components were assessed before and after the intervention., Results: There was no significant difference in BDNF level between the CFT and the CON group. In contrast, IGF-1, walking speed, and strength of the right- and left-hand was significantly increased in the CFT compared with the CON group. Furthermore, there was a significant and positive correlation between IGF-1 and some fitness components., Conclusions: The findings indicated that CFT might a useful training mode in the rehabilitation of the MS women. CFT improved IGF-1 level that is a neuroprotective agent in MS. Positive and significant association between IGF-1 and some health-related fitness components indicates of the importance of IGF-1 in the rehabilitation of the MS persons than BDNF., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The prevalence of major depressive disorder (MDD) is higher in women than men. Importantly, a differential behavioral response by sex to the antidepressant response to ketamine in rodents has been reported. Mechanistically, male depressed-like animals showed an increased spine density after ketamine treatment via restoration of synaptic protein levels while those proteins were not altered in female rats. In addition, preclinical studies indicate that the impairment of astrocytic plasticity is one of the contributing mechanisms in the pathophysiology of MDD. Accordingly, in this study, we determined the effect of sex on the rapid morphological alteration of hippocampal astrocytes and the serum level of BDNF one hour after S-ketamine injection. A single intraperitoneal dose of S-ketamine (15 mg/kg) or saline was injected to the male and female Flinders Sensitive Line (FSL) rats, a genetic animal model of depression and their brains were perfused one hour after treatment. The size of the GFAP positive astrocytes in the hippocampal subregions was measured. The volume of different hippocampal subregions was assessed using the Cavalieri estimator. Moreover, serum levels of BDNF were measured with enzyme-linked immunosorbent assay (ELISA) kits. The volume of hippocampal subregions significantly increased one hour after S-ketamine in both male and female FSL animals. However, a substantial alteration in the morphology of the hippocampal astrocytes was observed only in the female rats. Additionally, significantly increased serum BDNF levels in the female depressed rats were observed one hour after S-ketamine treatment. Our results indicate that the rapid effects of S-ketamine on the morphology of the hippocampal astrocytes and the serum level of BDNF are sex-dependent., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier B.V. and ECNP. All rights reserved.)

Disruption of brain-derived neurotrophic factor (BDNF) biosynthesis and/or signaling has been implicated in the pathogenesis of Alzheimer's disease (AD). We used postmortem brain and fluid samples from 20 patients with variable severity of AD and 11 controls to investigate whether BDNF levels in serum and brain tissue correlated with hippocampal pathology. Total BDNF, precursor BDNF (pro-BDNF), and mature BDNF were measured in cerebrospinal fluid, serum, and 3 postmortem brain regions. Histological markers for AD pathology, the BDNF cognate receptor (TrkB), and glia were measured in the hippocampus (HIP). Lower pro-BDNF levels were observed in the entorhinal and frontal cortices in AD cases compared with controls. AD cases also exhibited significantly lower staining densities of the cognate BDNF receptor TrkB in the HIP compared with controls, and TrkB staining was inversely correlated with both Amylo-Glo and pTau staining in the same region, suggesting a relationship between the density of the cognate BDNF receptor and accumulation of AD pathology. In addition, higher serum pro-BDNF levels correlated with lower HIP pro-BDNF levels and higher pTau staining in the HIP. Total BDNF levels in cortical regions were also negatively correlated with Amylo-Glo staining in the HIP suggesting that reduced BDNF cortical levels might influence hippocampal amyloid accumulation. These results strongly suggest that altered BDNF and TrkB receptors are involved in AD pathology and therefore warrant investigations into therapies involving the BDNF pathway., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: While acute neurotoxic side effects of calcineurin inhibitors (CNI) are well-known, data upon long-term effects on brain structure and function are sparse. We hypothesize that long-term CNI therapy affects the neuroimmune system, thereby, increasing the risk of neurodegeneration. Here, we measured the impact of CNI therapy on plasma levels of brain- and T cell-derived cytokines in a cohort of patients after liver transplantation (LT)., Methods: Levels of T cell-mediated cytokines (e.g. Interferon-γ (IFN-γ)) and brain-derived cytokines (e.g. brain derived neurotrophic factor (BDNF), platelet derived growth factor (PDGF)) were measured by multiplex assays in plasma of 82 patients about 10 years after LT (17 with CNI free, 35 with CNI low dose, 30 with standard dose CNI immunosuppression) and 33 healthy controls. Data were related to psychometric test results and parameters of cerebral magnetic resonance imaging., Results: IFN-γ levels were significantly higher in the CNI free LT patient group (p=0.027) compared to healthy controls. BDNF levels were significantly lower in LT patients treated with CNI (CNI low: p<0.001; CNI standard: p=0.016) compared to controls. PDGF levels were significantly lower in the CNI low dose group (p=0.004) and for PDGF-AB/BB also in the CNI standard dose group (p=0.029) compared to controls. BDNF and PDGF negatively correlated with cognitive function and brain volume (p<0.05) in the CNI low dose group., Conclusion: Our results imply that long-term treatment with CNI suppresses BDNF and PDGF expression, both crucial for neuronal signaling, cell survival and synaptic plasticity and thereby may lead to cognitive dysfunction and neurodegeneration., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Hypothalamic pathology is a well-documented feature of Huntington's disease (HD) and is believed to contribute to circadian rhythm and habitual sleep disturbances. Currently, no therapies exist to combat hypothalamic changes, nor circadian rhythm and habitual sleep disturbances in HD., Objective: To evaluate the effects of multidisciplinary rehabilitation on hypothalamic volume, brain-derived neurotrophic factor (BDNF), circadian rhythm and habitual sleep in individuals with preclinical HD., Methods: Eighteen individuals with HD (ten premanifest and eight prodromal) undertook a nine-month multidisciplinary rehabilitation intervention (intervention group), which included exercise, cognitive and dual task training and social events, and were compared to a community sample of eleven individuals with premanifest HD receiving no intervention (control group). Hypothalamic volume, serum BDNF, salivary cortisol and melatonin concentrations, subjective sleep quality, daytime somnolence, habitual sleep-wake patterns, stress and anxiety and depression symptomatology were evaluated., Results: Hypothalamus grey matter volume loss was significantly attenuated in the intervention group compared to the control group after controlling for age, gender, Unified Huntington's Disease Rating Scale-Total Motor Score and number of cytosine-adenine-guanine repeats. Serum BDNF levels were maintained in the intervention group, but decreased in the control group following the study period. Both groups exhibited decreases in cortisol and melatonin concentrations. No changes were observed in sleep or mood outcomes., Conclusions: This exploratory study provides evidence that multidisciplinary rehabilitation can reduce hypothalamic volume loss and maintain peripheral BDNF levels in individuals with preclinical HD but may not impact on circadian rhythm. Larger, randomised controlled trials are required to confirm these findings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Brain-derived neurotrophic factor (BDNF) participates in orchestrating the adaptive response to exercise. However, the importance of transient changes in circulating BDNF for eliciting whole-body and skeletal muscle exercise benefits in humans remains relatively unexplored. Here, we investigated effects of acute aerobic exercise and 3-month aerobic-strength training on serum, plasma and skeletal muscle BDNF in twenty-two sedentary older individuals (69.0 ± 8.0 yrs., 9 M/13F). BDNF response to acute exercise was additionally evaluated in young trained individuals (25.1 ± 2.1 yrs., 3 M/5F). Acute aerobic exercise transiently increased serum BDNF in sedentary (16%, p = .007) but not in trained elderly or young individuals. Resting serum or plasma BDNF was not regulated by exercise training in the elderly. However, subtle training-related changes of serum BDNF positively correlated with improvements in walking speed (R = 0.59, p = .005), muscle mass (R = 0.43, p = .04) and cognitive performance (R = 0.41, p = .05) and negatively with changes in body fat (R = -0.43, p = .04) and triglyceridemia (R = -0.53, p = .01). Individuals who increased muscle BDNF protein in response to 3-month training (responders) displayed stronger acute exercise-induced increase in serum BDNF than non-responders (p = .006). In addition, muscle BDNF protein content positively correlated with type II-to-type I muscle fiber ratio (R = 0.587, p = .008) and with the rate of post-exercise muscle ATP re-synthesis (R = 0.703, p = .005). Contrary to serum, acute aerobic exercise resulted in a decline of plasma BDNF 1 h post-exercise in both elderly-trained (-34%, p = .002) and young-trained individuals (-48%, p = .034). Acute circulating BDNF regulation by exercise was dependent on the level of physical fitness and correlated with training-induced improvements in metabolic and cognitive functions. Our observations provide an indirect evidence that distinct exercise-induced changes in serum and plasma BDNF as well as training-related increase in muscle BDNF protein, paralleled by improvements in muscle and whole-body clinical phenotypes, are involved in the coordinated adaptive response to exercise in humans., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: To investigate the effects of mold-fermented cheese (MFC) on brain-derived neurotrophic factor (BDNF) in community-dwelling older Japanese women with mild cognitive impairment (MCI)., Design: Randomized controlled crossover trial., Intervention: Participants were randomly assigned to 2 groups. The MFC group was provided with 33.4 g MFC (camembert cheese) daily for 3 months, and the non-MFC group was provided with the same amount of non-MFC (processed cheese made from mozzarella cheese and cream cheese) for 3 months. After the post-intervention analysis (primary analysis), there was a 3-month washout period, followed by a crossover period (secondary analysis)., Setting and Participants: Urban community in Tokyo, Japan. A total of 71 older women aged ≥70 years with MCI based on selected criteria in 689 community-dwelling women., Measures: Face-to-face interviews were conducted to administer the Geriatric Depression Scale (GDS) and Mini-Mental State Examination (MMSE) and collect data on medical history. Physical function measures included grip strength, knee extension strength, and usual walking speed. Blood samples were obtained to determine the levels of albumin, vitamin D, high-sensitivity C-reactive protein, and BDNF., Results: Significant interactions were observed in BDNF after intervention of MFC intake in the secondary (F = 5.368, P = .024) and combined analyses (F = 4.354, P = .039) but not the primary analysis. There were no significant changes in the 3 categories of MMSE score (normal, MCI, moderate or severe cognitive impairment), GDS score, physical function, and blood indicators., Conclusions and Implications: Three months of MFC ingestion had beneficial effects on BDNF levels in community-dwelling older women with MCI; however, the BDNF increases did not translate into MMSE scores. Further study into the effects of interventions on cognitive function and depression in older people with MCI is necessary., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

The etiology of depression is not known, it is thought that endocrine-disrupting chemicals (EDCs) contribute to the disease. Results of our previous research have shown that nonylphenol (NP), a well-known EDC, has neurotoxic effects, however, whether NP can induce depressive behavior by affecting synaptic plasticity has not yet been clearly elucidated. The depressive behavior induced by subchronic exposure to NP and its effect on the neuronal synaptic plasticity in rats are dynamically observed. Thirty Sprague-Dawley rats were randomly divided into 3 groups: control group (C, corn oil), NP group (NP, 4 mg/kg), and depression model group (D, corticosterone 20 mg/kg). There were 8 rats in each group. The depressive behavior of rats was tested by sucrose preference test, open-field test, and forced swimming test once a month for 3 months. The serum levels of brain-derived neurotrophic factor (BDNF) and corticosterone were detected by ELISA assay, and cellular morphological changes were observed by hematoxylin-eosin (HE) staining. The number of nerve cells, the length of dendrites, and the density of dendritic spines were observed by Golgi staining, and the synaptic cleft width, the postsynaptic density (PSD) thickness, and the synaptic interface curvature were observed by transmission electron microscope. Compared with the control group, the consumption of sucrose solution decreased in the NP group at the 2nd and 3rd month compared to the 1st month (F = 9.887, P = 0.002). The number of central square entries, the central square duration, and the total distance of movement were all decreased, and the decreasing degrees at the 3rd month were greater than those at the 1st month (F = 21.191, P < 0.001; F = 9.836, P = 0.002). The time of immobility for the NP group at the 1st month was higher than that in the control group (F = 6.912, P = 0.002). The expression of BDNF in the NP-treated group was higher than the control, while the expression of corticosterone in the NP-treated group was lower than the control. In the NP group, the cytoplasm of nerve cells contracted and appeared disordered. The neuron arrangement was disordered, and the number of cells, the length of the apex, the length of the basal dendrites, and the dendritic spine density were all lower in the NP group than those in the control group. The PSD thickness, the synaptic cleft width, and synaptic interface curvatures were all decreased in the NP group when compared to the control group. Subchronic exposure to 4 mg/kg NP led to depressive behavior in rats, and the depressive behavior and alterations in synaptic plasticity were more obvious with longer exposure time., (Copyright © 2019. Published by Elsevier B.V.)

Background: The outcome of methadone maintenance therapy (MMT) varies in each patient with opioid use disorder (OUD). Opioid abuse activates proinflammatory processes by increasing cytokine production and impairing neurotrophic factor expression, and possibly leads to a vicious cycle that hinders recovery. Therefore, we investigated whether markers of inflammation and neurotrophic expression correlate with the MMT outcomes in OUD patients., Method: We investigated OUD patients undergoing MMT and followed them up for 12 weeks. We measured plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, IL-1β, transforming growth factor (TGF)-β1, brain-derived neurotrophic factor (BDNF), urinary morphine tests, and plasma morphine levels at baseline and on weeks 1, 4, 8, and 12 during MMT. Multiple linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the cytokine and BDNF levels and MMT outcomes., Results: We initially enrolled 104 patients, but only 78 patients completed end-of-study assessments. Plasma levels of CRP, TGF-β1, and BDNF fell during MMT. Plasma IL-6 levels were significantly associated with plasma morphine levels (P = 0.005) and urinary morphine-positive ( + ) results (P = 0.04), and significantly associated with poor compliance (P = 0.009) and early dropout from MMT (P = 0.001). However, other cytokine and BDNF levels were not consistently associated with MMT outcomes., Conclusion: Higher IL-6 levels were associated with poor MMT outcomes. Additional studies on regulating IL-6 expression to improve treatment outcomes in OUD patients might be warranted., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity and in the pathophysiology of various brain disorders. Repetitive transcranial magnetic stimulation (rTMS) has been widely used in neuropsychiatric disease. It is presumed that BDNF mediates the therapeutic benefits of rTMS, but previous results are contradictory. We therefore conducted a meta-analysis to examine the efficacy of rTMS to increase serum BDNF., Methods: We performed a comprehensive literature search for clinical trials evaluating the efficacy of rTMS and addressing serum BDNF level. To pool effect size estimate (Hedges' g) of serum BDNF across studies, a meta-analysis was performed according to the Cochrane guideline., Results: rTMS failed to increase serum BDNF level with effect size of -0.12 (95% CI: -0.30, 0.06) (P=0.193). Multilevel mixed-effects models analysis showed that overall effect of rTMS on BDNF levels was influenced by group of participants (healthy vs. disease) (P<0.001), stimulation frequency (low-frequency vs. high-frequency) of rTMS (P=0.007), treatment duration (P<0.001) of rTMS, and population age (P<0.001)., Conclusions: Repetitive rTMS fails to increase serum BDNF, and it seems that serum BDNF level is related to frequency and duration of rTMS, as well as age and health status of population., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Introduction: The induction of brain-derived neurotrophic factor (BDNF) release and subsequent restoration of neuroplastic homeostasis may underlie the effects of electroconvulsive therapy (ECT)., Objectives: We aimed to assess serum and plasma BDNF levels during the course of acute ECT, as well as before and after subsequent continuation ECT, in patients with depression., Methods: We included 24 patients with major depressive disorder (mean age ± SD: 54.5 ± 13.7; f/m: 17/7; baseline 17-item Hamilton Depression Rating Scale score of 26.79 ± 4.01). Serum and plasma BDNF (sBDNF, pBDNF) levels were assessed at nine time-points before, during, and after acute ECT series. Data were analysed using linear regression and linear mixed models, which were adjusted for multiple comparisons via Bonferroni correction. Five patients received continuation ECT subsequent to the acute ECT series. In these patients, BDNF levels were assessed before and after each two continuation ECT sessions using Wilcoxon signed-rank tests., Results: Relative to baseline (mean ng/ml ±SD: 24.68 ± 14.40), sBDNF levels were significantly higher 1 day (33.04 ± 14.11, p = 0.013, corrected), 1 week (37.03 ± 10.29, p < 0.001, corrected), and 1 month (41.05 ± 10.67, p = 0.008, corrected) after the final ECT session, while pBDNF levels did not significantly differ (p > 0.1). Furthermore, our results indicated that sBDNF levels increased after each continuation ECT session. There was no significant association between sBDNF levels and clinical parameters or treatment response., Conclusion: The absence of an association between changes in sBDNF levels and depressive symptoms challenges the proposed concept of sBDNF/pBDNF as key markers of the effects of ECT., (Copyright © 2019. Published by Elsevier Inc.)

The main aim of this study is to evaluate the impact of functional remediation (FR) in serum brain derived neurotrophic factor (BDNF) levels in euthymic adult patients with Bipolar Disorder (BD). A total of 128 participants were recruited at the Hospital Clinic of Barcelona. They were assessed at baseline and at the end of follow-up by the means of Hamilton Depression Scale (HAM-D), Young Mania Rating Scale (YMRS) and Functioning Assessment Short Test (FAST), as well as a clinical structured interview to collect clinical and demographic variables of interest. Blood samples were also collected to assess BDNF levels. After baseline assessment, patients received FR, Psychoeducation or treatment as usual (TAU). One hundred and two out of 126 participants finished the study distributed as follows: FR group (n = 39); Psychoeducation group (n = 47) and TAU group (n = 16). Longitudinal repeated-measures analyses addressing the treatment effect on BDNF levels showed non-significant differences between the three groups (Pillai's trace = 0.06; F (2,97) = 0.28; p = 0.75), suggesting no interaction between treatment allocation and time on BDNF levels. The results of this study suggest that FR has no effect on peripheral BDNF levels in euthymic patients with BD, despite the improvement in psychosocial functioning., (Copyright © 2019. Published by Elsevier B.V.)

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism may be an important source of heterogeneity seen in cognitive aging, although the specific relationship between this polymorphism and cognition remains controversial and may depend on the sex of participants. We assessed 2668 older black and white adults and fit linear mixed models to digit symbol substitution test (DSST) performance assessed in years 0 (baseline), 4, 7, and 9 to examine the interaction between sex and BDNF genotype on the intercept (i.e., estimated baseline DSST) and change in DSST over 9 years, adjusted for covariates. Sex interacted with BDNF genotype to predict DSST intercept (F[1,1599] = 7.4, p < 0.01) and 9-year change (F[1,1183] = 4.1, p = 0.04) in white participants only. Initially, white male Val/Val carriers had lower DSST scores (37.6, SE = 0.8) in comparison with male Met carriers (difference, -1.7; 95% CI, -3.2 to -0.3) and female Val/Val carriers (difference, -5.6; 95% CI, -6.8 to -4.3). White female Met carriers showed a slower rate of change (annual rate of change = -0.6, SE = 0.1) in comparison with female Val/Val carriers (difference, -0.2; 95% CI, -0.4 to -0.02) and male Met carriers (difference, -0.3; 95% CI, -0.5 to -0.02). Our findings suggest that BDNF Val66Met and sex should be considered in future endeavors aimed at treating or preventing neurodegenerative disorders., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Brain-derived neurotrophic factor (BDNF) is associated with several neurodegenerative and psychiatric disorders. It is not clear, however, whether BDNF levels are modified in substance use disorders (SUDs)., Methods: We conducted a systematic search of electronic databases to identify studies comparing peripheral plasma or serum BDNF levels in adults with SUDs vs. non-user controls. Forty studies were included in the meta-analysis involving a total of 2238 participants with SUDs and 2574 controls., Results: After trim and fill adjustment, current drug users presented lower serum BDNF levels (SMD = -0.99, 95%CI -1.40 to -0.58, I 2  = 95.9) than non-user controls. However, this difference disappears during withdrawal. Studies using serum or plasma BDNF samples have shown different results. Subgroup analysis revealed lower levels of serum BDNF in alcohol users (SMD = -0.70, 95%CI -1.15 to -0.25, I 2  = 89.81) and crack/cocaine users (SMD = -1.78, 95%CI -2.92 to -0.65, I 2  = 97.59) than controls. Meta-regression analysis revealed that gender, age, and age of first use moderate the effects of drug use in peripheral BDNF levels., Conclusions: Peripheral BDNF levels are decreased in the serum, but not the plasma, of active drug users. Altogether, these findings suggest that BDNF levels may be related to acute use and addiction severity and also point to BDNF's potential utility as a biomarker in this population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The identification of biomarkers associated with obesity and response to treatment could represent an important advance to design more effective and personalized therapeutic strategies. The complexity of morbid obesity could be explained as the combination of genetic, biochemical, cultural, and behavioral factors, among others. The study of biomarkers should be considered a determinant factor taken into account in this equation., Objectives: The aim of this study was to define better biomarker profiles potentially associated to the short-term outcome of bariatric surgery by paying attention to cocaine and amphetamine regulated transcript and brain-derived neurotrophic factor, 2 neuropeptides related to eating behavior., Setting: University General Hospital of Ciudad Real, Spain., Methods: Twenty-seven morbidly obese patients and 30 healthy weight individuals matched by age and sex were selected for the study., Results: Patients underwent bariatric surgery by Roux-en-Y gastric bypass and responded adequately in terms of weight loss and normalization of many biochemical parameters 1 year postsurgery. A multivariate analysis showed that the hormonal/neuropeptidic profile explained 82% of the variability of the weight loss response. The evolution of cocaine and amphetamine regulated transcript paralleled that of insulin and leptin, serum levels of this peptide were initially elevated in patients (4.24 ± .47 ng/mL) with respect to controls (2.94 ± .2 ng/mL), but this difference disappeared 1 year after Roux-en-Y gastric bypass (3.14 ± .26 ng/mL). Brain-derived neurotrophic factor levels were also decreased by Roux-en-Y gastric bypass (11.93 ± .96 ng/mL postsurgery versus 15.3 ± 1.02 ng/mL presurgery), even when this peptide was not elevated in patients before surgery (14.23 ± .86 ng/mL in controls)., Conclusions: The results suggest that cocaine and amphetamine regulated transcript and brain-derived neurotrophic factor could be envisaged as new candidate biomarkers of short-term outcome after surgery., (Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Environment enrichment is a rising topic for animal welfare but measures to identify effective enrichment interventions are lacking. In humans and rodent species, environmental enrichment increases brain-derived neurotrophic factor (BDNF), the most abundant neurotrophin in the brain. Higher BDNF concentration is ultimately linked to higher stress resilience, and BDNF in the hippocampus enhances learning and memory. In addition, BDNF concentrations in the brain and blood are correlated, offering the opportunity to use peripheral BDNF as a minimally invasive measure of effective enrichment reflecting neural changes. This study investigated changes in serum BDNF following the provision of environmental enrichment to pigs. Pigs were housed in different environments during lactation (enriched vs barren) and after weaning (enriched vs barren), using a 2 × 2 factorial design and the provision of a foraging block as enrichment. Pigs provided with foraging enrichment during lactation or after weaning tended to have higher serum BDNF concentrations than pigs housed in a barren environment, and this effect was significant for pigs enriched during lactation when sampled 5 wk after weaning. Brain-derived neurotrophic factor concentration reduced as the pigs aged from 3 to 11 wk. The measurement of BDNF in serum brings a practical approach to study the effects of environmental enrichment on neurobiological changes in domestic animals. A better understanding of the factors modulating BDNF and its link to welfare states could bring insight into the benefits of stimulating an animal's life., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Inflammation and trophic factors (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor-1) are associated with depression in the general population. Rheumatoid arthritis (RA) is a chronic representative inflammatory autoimmune disease; however, the association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression has not been sufficiently investigated. Therefore, we determined the prevalence of depression and risk factors for depression and deterioration of depressive symptoms in RA patients. In addition, we analyzed the association between disease activity, pro-inflammatory cytokines, trophic factors, and depression in RA (N = 474). Demographic and laboratory data were examined, and routine assessment of patient index data 3 (RAPID 3) and disease activity score 28-joint count C-reactive protein (DAS 28-CRP) was performed to assess disease activity of RA. Depression was measured using the Korean version of the Beck Depression Inventory-second edition (K-BDI II). A K-BDI score ≥18 was considered the cut-off for depression in accordance with a previous validation study. The serum level of pro-inflammatory cytokines and neurotrophic factors was assessed by enzyme-linked immune sorbent assay. The prevalence of depression was 32.4% in patients with RA. The severity of disease activity of RA (RAPID 3 score [OR 2.34; 95% confidence interval, CI 1.22-4.51], DAS 28-CRP [≥3.2] [OR 1.60, 95% CI 1.01-2.53]) and severity of fatigue (OR 1.26 95% CI 1.15-1.38) were associated with depression and deterioration of depressive symptoms in the multivariate analysis. Among the components of RAPID 3 and DAS 28-CRP, patient assessment for global health and abilities for daily performance were more related to depression. The level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-alpha) was not related to depression. The level of BDNF was significantly lower in RA patients with depression and was negatively correlated with K-BDI II score. Depression was related with the level of fatigue, low expression of BDNF, and high RA disease activity, which was associated with impaired ability to perform activities of daily life. Strict control of fatigue and disease activity to improve one's capacity to perform daily life activities would be important to regulate depression. The level of BDNF might be one of the possible biomarkers to predict or monitor depression in patients with RA., (Copyright © 2018. Published by Elsevier Inc.)

Background: Patients with opioid use disorder (OUD) show memory deficiencies and impaired treatment outcomes. Emerging evidence suggests that opioid abuse activates proinflammatory processes by increasing cytokine production and impairing neuroprotection, which damages the memory function in OUD patients. Therefore, we investigated whether plasma-based inflammatory and neurotrophic markers correlate with memory function in OUD patients., Method: OUD patients undergoing methadone maintenance therapy (MMT) were investigated and followed up for 12 weeks. Plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, transforming growth factor (TGF)-β1, brain-derived neurotrophic factor (BDNF) levels, and Wechsler Memory Scale-Revised (WMS-R) scores were assessed at baseline and after 12 weeks of MMT. Multiple linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between cytokines and memory performance., Results: We enrolled 89 patients at baseline; 47 patients completed the end-of-study assessments. Although Pearson correlations showed that CRP and TGF-β1 levels were significantly, negatively associated with some memory indices, the results were not significant after correction. The GEE results, controlled for several confounding factors and multiple testing, showed that changes in TNF-α levels were negatively correlated with changes in the visual memory index (P = 0.01), and that changes in IL-6 levels were negatively correlated with changes in the verbal memory index (P = 0.009)., Conclusion: Memory performance, TNF-α, and IL-6 levels in OUD patients were negative correlated. Additional studies on regulating TNF-α and IL-6 expression to improve memory function in OUD patients might be warranted., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Brain derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression and the antidepressant response. Electroconvulsive therapy (ECT) is reported to increase BDNF levels in blood, though only a small number of studies have been conducted to date., Objective: Our objectives were to: 1) compare plasma BDNF levels in medicated patients with depression and controls; 2) assess the effect of ECT on plasma BDNF levels in medicated patients with depression; 3) explore the relationship between plasma BDNF levels and the Val66Met (rs6265) BDNF polymorphism; and 4) examine the relationship between plasma BDNF levels and clinical symptoms and outcomes with ECT., Methods: Plasma BDNF levels were analyzed in samples from 61 medicated patients with a major depressive episode and 50 healthy controls, and in patient samples following a course of ECT. Fifty-two samples from the depressed patient group were genotyped for the Val66Met BDNF polymorphism., Results: There was no difference in plasma BDNF levels between the control and depressed groups, and there was no difference in plasma BDNF levels in patients following treatment with ECT. In line with previous reports, we show that, in medicated patients with depression, Met-carriers had higher plasma BDNF levels than Val-carriers, though genotype was not related to clinical response. We found no association between plasma BDNF levels and depression severity or the clinical response to ECT., Conclusions: Our results suggest that plasma BDNF does not represent a suitable candidate biomarker for determining the therapeutic response to ECT., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Cognitive impairment is considered a frequent side effect in the drug treatment of epilepsy. The objective of the present study was to investigate the effects of lacosamide (LCM) on learning and memory processes in rats, on the serum level of brain-derived neurotrophic factor (BDNF) and BDNF/TrkB ligand receptor system expression in the hippocampal formation. Male Wistar rats underwent long-term treatment with three different doses of lacosamide - 3 mg/kg (LCM 3), 10 mg/kg (LCM 10) and 30 mg/kg (LCM 30). All rats were subjected to one active and one passive avoidance tests. The BDNF/TrkB immunohistochemical expression in the hippocampus was measured and serum BDNF was determined. The LCM-treated rats made fewer avoidance responses than controls during acquisition training and in the memory retention test. The number of escapes in the LCM 10 and LCM 30 groups decreased throughout the test, while the rats in the LCM 3 group showed fewer escapes only in the memory test in the active avoidance task. In the step-down test, the latency time of the LCM-30 treated rats was reduced as compared with the controls during the learning session and the short- and long-term memory retention tests. Lacosamide induced a dose-dependent reduction of the hippocampal expression of BDNF and its receptor TrkB. We found no significant difference between BDNF serum levels in the test animals and controls. The results of the study suggest that LCM suppresses the learning and memory processes in rats, with the inhibition of hippocampal BDNF/TrkB ligand receptor system being one of the possible mechanisms causing this effect., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To study the effects of intermittent whole-body hypoxic preconditioning on patients with carotid artery stenosis., Methods: Fifty patients with carotid artery stenosis were selected and randomly divided into a hypoxic intervention group (HIG) and a control group (CG). Both groups were treated with a hypoxic respiration device for 7 days (HIG: 18% oxygen, CG: 21% oxygen). Venous blood samples were taken preoperatively and postoperatively. The subjects' vital signs were recorded during and after the intervention. After the completion of the trial, the concentrations of hemoglobin, hypoxia inducible factor-1α, erythropoietin, vascular endothelial growth factor, neuron-specific enolase, S100β protein, brain-derived neurotrophic factor, serum aspartate transaminase, serum alanine aminotransferase, serum creatinine, and blood urea nitrogen were measured in the previously selected blood samples., Results: During the intervention, the vital signs of the HIG were significantly different from those of the CG (P < 0.05). In the HIG, postoperative concentrations of hemoglobin, erythropoietin, hypoxia inducible factor-1α, and vascular endothelial growth factor were significantly more than the preoperative values (P < 0.05). In the CG, postoperative concentrations of neuron-specific enolase and S100β protein were more than the preoperative values (P < 0.05). The concentrations of brain-derived neurotrophic factor, serum aspartate transaminase, serum alanine aminotransferase, serum creatinine, and blood urea nitrogen showed no significant differences between their preoperative and postoperative values in either the HIG or the CG (P > 0.05)., Conclusions: Intermittent hypoxic preconditioning can change the vital signs and hematologic indexes of patients with carotid artery stenosis without causing new postoperative complications or organ damage., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The biological basis of suicide and suicidal behavior is actively researched. Recently, the role of Brain Derived Neurotropic Factor (BDNF) in suicidal behavior has gained attention and significant results are observed. In this review, we aimed to focus on the studies from Asian countries that have explored the role of BDNF and suicidal behavior. The review highlights the findings from these studies and discusses the possible avenues that should be explored in future studies from Asian countries to understand more on suicidal behavior and possible prevention., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Arterial stiffening blunts postprandial vasodilatation. We hypothesized that brain-derived neurotrophic factor (BDNF) may modulate postprandial central pulse pressure, a surrogate marker for arterial stiffening., Methods: A total of 82 non-diabetic subjects received a 75-g oral glucose tolerance test (OGTT) after overnight fasting. Serum BDNF concentrations were determined at 0, 30, and 120min to calculate the area under the curve (AUC). Brachial and central blood pressures were measured using a noninvasive central blood pressure monitor before blood withdrawals at 0 and 120min., Results: With the median AUC of BDNF of 45(ng/ml)∗h as the cutoff value, the central pulse pressure after glucose intake was significantly higher in the subjects with a low BDNF than in those with a high BDNF (63±16 vs. 53±11mmHg, P=0.003), while the brachial pulse pressure was not significantly different between the 2 groups (P=0.099). In a multivariate linear regression model, a lower AUC of BDNF was an independent predictor of a higher central pulse pressure after oral glucose intake (linear regression coefficient-0.202, 95% confidence interval-0.340 to -0.065, P=0.004)., Conclusion: After oral glucose challenge, a lower serum BDNF response is significantly associated with a higher central pulse pressure., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Multiple Sclerosis (MS) is a complex autoimmune neuro-inflammatory disorder characterized by persistent MS plaques in the central nervous system. Resolution of MS plaques is dependent on the remyelination competence of surviving oligodendrocytes and surrounding environment. Here, we assessed myelination modulators in a 100 MS patients against 77 healthy controls. Plasma fractions were used for the assessment of insulin growth factor binding protein1 (IGFBP1), brain-derived neurotrophic factor (BDNF), and lipocalin2 (LCN2) using a Luminex multiplex assay, whereas neurofilament light chain (NF-L) was assessed with an enzyme-linked immunosorbent assay. Circulating levels of IGFBP1, LCN2 and NF-L were significantly higher in MS patients (p<0.01). Whereas BDNF levels were significantly lower in MS patients (p=0.014). MS Female patients had significantly higher levels of IGFBP1 compared to male MS patients (p=0.006). MS patients treated with fingolimod had higher LCN2 levels compared to those on natalizumab (r=0.25, p=0.03). Higher NF-L levels associated with clinically isolated syndrome's (CIS) conversion into MS (p=0.002). We conclude that low BDNF and high LCN2 and NF-L levels are associated with MS pathogenesis, and high IGFBP1level is a biomarker for female MS only, suggesting different MS progression pathways between the sexes. LCN2 is a candidate predictor of response to natalizumab treatment, and NF-L is a candidate predictor of CIS conversion into MS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Multisensory integration of visuo-tactile information presented on the body or a dummy body has a strong impact on body image. Previous researches show that alteration of body image induced by visuo-tactile integration is closely related to the activation of the parietal cortex, a sensory association area. The expression of brain-derived neurotrophic factor (BDNF) in the parietal area of macaque monkeys is thought to modulate the activation of the parietal cortex and alter the extension of body image during tool-use learning. However, the relationship between parietal cortex activation related to body image alterations and BDNF levels in humans remains unclear. We investigated the relationship between human serum BDNF levels and electroencephalography responses during a visuo-tactile integration task involving a rubber hand. We found cortical oscillatory components in the high frequency (gamma) band in the left parietal cortex. Moreover, the power values of these oscillations were positively correlated (p<0.05) with serum BDNF levels. Our results suggest that serum BDNF could play a role in modulating the cortical activity in response to visuo-tactile integration processes related to body image alteration in humans., (Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.)

Background: Depression is one of the important world-wide health problems., Objectives: This study aimed to assess the ameliorative effect of Ocimum basilicum (OB) essential oil on the behavioral, biochemical and histopathological changes resulted from exposure to chronic unpredictable mild stress (CUMS). It also aimed to investigate the underlying mechanism in an animal model of depression., Materials and Methods: Forty male Swiss albino mice were divided into four groups (n=10): control, CUMS (exposed to CUMS for 4weeks), CUMS plus fluoxetine, and CUMS plus OB. At the end of the experiment, behavioral changes, serum corticosterone level, protein and gene expressions of brain derived neurotropic factor (BDNF) and glucocorticoid receptors (GR) in the hippocampus was all assessed. Immunoexpression of surface makers of glial fibrillary acidic protein (GFAP), Ki67, Caspase-3, BDNF and GR in the hippocampus were estimated. Data were analyzed by using the statistical package for the social sciences (SPSS)., Results: OB alleviated both behavioral and biochemical changes recorded in mice after exposure to CUMS. It also reduced neuronal atrophy observed in the hippocampal region III cornu ammonis (CA3) and dentate gyrus and restored back astrocyte number. OB decreased apoptosis in both neurons and glial cells and increased neurogenesis in the dentate gyrus in a pattern comparable to that of fluoxetine. Increased BDNF and GR gene and protein expressions seems to be behind the antidepressant-like effect of OB., Conclusion: Ocimum basilicum ameliorates the changes induced after exposure to the chronic stress. Assessing Ocimum basilicum efficacy on human as antidepressant is recommended in further studies., (Copyright © 2017. Published by Elsevier Inc.)

Background: Delirium is common after surgery, although the aetiology is poorly defined. Brain-derived neurotrophic factor (BDNF) is a neurotrophin important in neurotransmission and neuroplasticity. Decreased levels of BDNF have been associated with poor cognitive outcomes, but few studies have characterized the role of BDNF perioperatively. We hypothesized that intraoperative decreases in BDNF levels are associated with postoperative delirium., Methods: Patients undergoing spine surgery were enrolled in a prospective cohort study. Plasma BDNF was collected at baseline and at least hourly intraoperatively. Delirium was assessed using rigorous methods, including the Confusion Assessment Method (CAM) and CAM for the intensive care unit. Associations of changes in BDNF and delirium were examined using regression models., Results: Postoperative delirium developed in 32 of 77 (42%) patients. The median baseline BDNF level was 7.6 ng ml -1 [interquartile range (IQR) 3.0-11.2] and generally declined intraoperatively [median decline 61% (IQR 31-80)]. There was no difference in baseline BDNF levels by delirium status. However, the percent decline in BDNF was greater in patients who developed delirium [median 74% (IQR 51-82)] vs in those who did not develop delirium [median 50% (IQR 14-79); P =0.03]. Each 1% decline in BDNF was associated with increased odds of delirium in unadjusted {odds ratio [OR] 1.02 [95% confidence interval (CI) 1.00-1.04]; P =0.01}, multivariable-adjusted [OR 1.02 (95% CI 1.00-1.03); P =0.03], and propensity score-adjusted models [OR 1.02 (95% CI 1.00-1.04); P =0.03]., Conclusions: We observed an association between intraoperative decline in plasma BDNF and delirium. These preliminary results need to be confirmed but suggest that plasma BDNF levels may be a biomarker for postoperative delirium., (© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com)