Between Brain-derived Neurotrophic Factor Levels Research Articles

Gender-modulated influence of BDNF concentration and Val66Met polymorphism on cognitive outcomes in chronic limb ischemia patients

IntroductionWhile numerous studies have established associations between brain-derived neurotrophic factor (BDNF) and cognitive functioning, limited research has delved into the role of BDNF concerning cognitive outcomes in atherosclerosis-related conditions. This study aimed to investigate the correlations between cognitive performance, serum BDNF levels, and the BDNF Val66Met polymorphism in individuals diagnosed with chronic limb ischemia (CLI).Participants and procedureThe study encompassed 159 CLI patients (52 females, 107 males) aged 59-73 years. Genetic analysis involved assessing the BDNF Val66Met single-nucleotide polymorphism using a TaqMan SNP Genotyping Assay and the ViiA™ 7 Real-Time PCR System. Serum BDNF levels were quantified. Cognitive functioning was evaluated through a computerized battery of tests, including the simple reaction test (SRT) for speed and accuracy assessment, verbal memory test (VMT) for short and long-term memory evaluation, and the GoNoGo test for cognitive control and inhibition.ResultsGender differences in cognitive performance were observed, with women excelling in VMT, while men demonstrated superior performance in SRT and the GoNoGo test. No statistically significant differences were noted between the Met/Met or Met/Val and Val/Val subgroups. However, notable differences emerged in female Met carriers, exhibiting superior VMT scores but more incorrect Go responses in the GoNoGo test. Conversely, female Val homozygotes showed significantly more incorrect NoGo responses compared to male Val homozygotes. In men carrying the Met allele, higher BDNF concentrations correlated with improved GoNoGo test results (r = 0.248, p = 0.01). Conversely, in women with the Val/Val variant, lower BDNF concentrations were associated with better VMT scores.ConclusionsThis study underscores the sex-specific impact of BDNF serum levels and the BDNF polymorphism on cognitive processes among CLI patients. The findings highlight the nuanced influence of BDNF in shaping cognitive functioning, emphasizing the need for further research into these sex-dependent associations.

The Relationship Between Brain-Derived Neurotrophic Factor and Serotonin in Major Depressive and Bipolar Disorders: A Cross-Sectional Analysis.

Background Mood disorders like major depressive disorder (MDD) and bipolar disorder (BD) involve complex interactions between brain-derived neurotrophic factor (BDNF) and serotonin. While extensive research has explored these factors individually, their combined effects and interactions in these disorders are less understood. This study uniquely addresses this gap by examining how BDNF and serotonin interact and relate to mood disorder severity, providing new insights into their joint role in MDD and BD. Objectives The objective of this study was to examine the correlation between serum BDNF and plasma serotonin levels and to assess how these correlations relate to the severity of symptoms and overall disease severity in MDD and BD. Methodology This cross-sectional study, conducted at the Khyber Medical University, Peshawar, from January to September 2023, examined the correlation between BDNF and serotonin in individuals with MDD and BD. Participants (n = 63) aged 18-65 were recruited based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, excluding those with neurological disorders, substance abuse, or severe medical illness. A control group of 21 healthy individuals was matched by age and gender. Data collection involved demographic details, clinical history, and comorbid diagnoses assessed using the Mini International Neuropsychiatric Interview (MINI). Mood disorder severity was measured using the Hamilton Depression Rating Scale (HAM-D) for MDD and the Young Mania Rating Scale (YMRS) for BD, along with additional assessments (Beck Depression Inventory, Global Assessment of Functioning). Serum BDNF and serotonin levels were analyzed using enzyme-linked immunosorbent assay (ELISA) kits. Statistical analyses included t-tests, Mann-Whitney U tests, Pearson correlations, and subgroup analyses to assess relationships between biomarkers, mood disorder severity, and influencing factors. Results BDNF levels were found to be 20.1 ± 5.3 ng/mL in MDD, 18.5 ± 4.7 ng/mL in BD, and 25.9 ± 6.2 ng/mL in controls. Serotonin levels were 45.8 ± 12.6 ng/mL in MDD, 43.2 ± 11.4 ng/mL in BD, and 52.1 ± 14.3 ng/mL in controls. In the MDD group, significant negative correlations were observed between BDNF levels and mood disorder severity (r = -0.32, p = 0.045), whereas serotonin levels did not show significant correlations (r = -0.21, p = 0.23). In the BD group, BDNF levels also showed a significant negative correlation with manic symptoms (r = -0.28, p = 0.048), but serotonin levels showed no significant correlation. Subgroup analyses revealed that participants under 40 years had higher BDNF levels (22.8 ± 5.6 ng/mL) compared to those aged 40 and above (19.7 ± 4.3 ng/mL). Females showed higher BDNF levels (24.5 ± 6.3 ng/mL) than males (19.3 ± 3.8 ng/mL). Participants not on medication had higher BDNF levels (23.6 ± 5.1 ng/mL) compared to those on medication (17.9 ± 4.2 ng/mL). Those without comorbidities also had higher BDNF levels (23.8 ± 5.9 ng/mL) than those with comorbidities (18.2 ± 4.5 ng/mL), while serotonin levels varied similarly across these subgroups. Conclusion Lower BDNF levels are associated with mood disorders and symptom severity, indicating their potential as a biomarker.

Relationship Between Serum Brain-Derived Neurotrophic Factor and Neurotrophin-3 Levels and Hearing Thresholds in Patients With Age-Related Hearing Loss.

Age-related hearing loss (ARHL) is a general term used to describe the sensorineural type of hearing loss occurring in both ears in older adults. Neurotrophins are the most promising candidates for supporting the auditory nerve by increasing neuronal survival. This study aimed to help elucidate the pathophysiology of ARHL by determining whether any relationship exists between brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) levels in serum samples from patients diagnosed with ARHL. Seventy-seven individuals, a study group of 41 patients diagnosed with ARHL, and a control group of 36 participants without hearing loss were evaluated. Serum samples were collected and used to measure serum BDNF and NT-3 levels with the new Nepenthe enzyme-linked immunosorbent assay method. Median pure-tone average results in the 2000, 4000, and 6000 Hz ranges were 52.5 (44.3-67.3) dB HL in the ARHL group and 13.5 (11.1-17.1) dB HL in the control group. The difference was statistically significant (p = .001). Although NT-3 and BDNF levels were both lower in ARHL patients than in participants without hearing loss, only the BDNF levels were significantly (p = .002) lower. Mean left and right ear word recognition scores were also lower in ARHL patients than in control groups. The ARHL group was further divided into two subgroups based on word recognition scores to evaluate significant differences in BDNF and NT-3 levels. No statistically significant difference was observed in BDNF and NT-3 levels between these subgroups. However, there was a significant difference in word recognition scores. Low BDNF levels in the ARHL group suggest that BDNF may play a role in the pathogenesis of ARHL. Patients with low (ARHL1) and high (ARHL2) word recognition scores were compared for the first time in the literature in terms of BDNF and NT-3 levels. However, the results were not statistically significant. This article is a preliminary study and was written to provide guidance for our next comprehensive project.

Brain-derived neurotrophic factor in the acute and early recovery period of ischemic stroke: the role of nocturnal hypoxemia

To study the relationship between brain-derived neurotrophic factor (BDNF) and the severity of nocturnal hypoxemia in patients in the acute and early recovery period of ischemic stroke (IS). We enrolled 44 patients (27 men, 17 women), aged 18-85 years, in the acute phase of IS. At 3-month follow-up, 35 people were examined (21 men and 14 women). In the acute period, in addition to routine diagnostic procedures, respiratory monitoring was carried out, and the serum level of BDNF was measured by enzyme-linked immunosorbent assay. BDNF level was also evaluated at 3-month follow-up visit. Neurological status and its dynamics in the acute period of stroke were assessed as part of the clinical routine according to the National Institutes of Health Stroke Scale (NIHSS) at admission and discharge. We found a direct correlation between the duration of hypoxemia with SpO2 less than 90% (r=0.327, p=0.035) and less than 85% (r=0.461, p=0.003) and BDNF level in the acute phase of IS. BDNF level in the acute period of IS was negatively correlated with the minimum saturation value (r=-0.328, p=0.034). There was a direct relationship between BDNF level in the early recovery period and the duration of hypoxemia with SpO2 less than 85% (r=-0.389, p=0.028). A regression model showed that BDNF level was associated with the minimum SpO2 level. No significant associations were found with indicators of sleep-disordered breathing severity, such as the apnea-hypopnea index and the oxygen desaturation index. The severity of nocturnal hypoxemia is associated with the increase in BDNF levels both in the acute and recovery periods of IS, regardless of the presence of concomitant breathing disorders during sleep.

Association between salivary mature brain-derived neurotrophic factor and psychological distress in healthcare workers.

Previous studies have suggested association between brain-derived neurotrophic factor (BDNF) and the stress level of workers. However, no studies have investigated the potential of salivary mature BDNF (mBDNF) level as a noninvasive biomarker for psychological distress. This study aimed to explore the reliability of salivary mBDNF as a biomarker for psychological distress in healthcare workers. Furthermore, we examined the relationship between salivary and plasma mBDNF levels and their correlation with age, sex, body mass index (BMI), and exercise habits. Fifty-one healthy healthcare workers (26 men) from the University of Occupational and Environmental Health, Japan, participated in this study. In this cross-sectional study, participants provided demographic information. Psychological distress was assessed using the Kessler 6 (K6). Saliva and blood samples were collected, and mBDNF was measured by ELISA. Spearman's rank correlation coefficient was performed to analyze the relationship between mBDNF (saliva and plasma) and K6. Statistical analyses were conducted using Stata 17.0, and a significance level of p<.05 was applied. The median K6 score was 1 (interquartile range [IQR]: 0-3). The median (IQR) salivary mBDNF was 1.36 (1.12-1.96)pg/mL, whereas the mean (standard deviation) plasma mBDNF was 1261.11 (242.98)pg/mL. No correlation was observed between salivary and plasma mBDNF concentrations or with the K6 score. Additionally, there were no associations between salivary or plasma mBDNF concentrations and age, sex, or exercise habits. Finally, an association between plasma mBDNF concentration and BMI was found only in univariate analysis. Our findings indicate that salivary mBDNF can be accurately measured noninvasively in healthcare workers. Within our study sample, salivary mBDNF did not demonstrate any correlation with K6 and plasma mBDNF. Future studies with a larger study sample and a diverse study population consisting of healthy participants and patients with psychiatric disorders are warranted.

Analysis of Changes in BDNF Levels Before and After Bariatric Surgery in Obese Patients

Objectives: The rate of obesity has been increasing globally, so is the number of obese patients undergoingbariatric surgery. The relationship between brain-derived neurotrophic factor (BDNF) and body weight has beenhighlighted in recent years, but there are few related studies in China. The purpose of this study was to investigate the changes of BDNF in obese patients before and after bariatric surgery and to provide evidence for obesity-related mechanisms. Methods: The BDNF levels in 44 obese patients who underwent bariatric surgery were measured by enzyme-linked immunosorbent assay (ELISA) before and 4.5 months after surgery. SPSS 27.0 was used for statistical analysis. Results: Among the 44 patients, 30 were female and 14 were male. The body mass index (BMI) decreased significantly after bariatric surgery (P &lt; 0.001); the serum BDNF of the patients significantly increased (P &lt; 0.001) after surgery. There was no significant difference in BDNF among patients with different degrees of obesity before and after surgery (P &gt; 0.05). There were no significant differences in BMI and BDNF levels between different sexes before and after surgery (P &gt; 0.05). Conclusion: The BDNF levels of obese patients increased significantly after bariatric surgery, which proved that bariatric surgery has an effect on BDNF levels.

Relationship between brain-derived neurotrophic factor serum levels with the severity of melasma.

Aim To determine the relationship between brain-derived neurotrophic factor (BDNF) levels and the severity of melasma. Methods This cross-sectional analytic study included consecutive patients from the Dermatology and Venereology Polyclinic at Prof. dr. Chairuddin Panusunan Lubis Universitas Sumatera Utara (Prof. dr. CPL USU) Hospital Medan from May to December 2022. Serum BDNF levels and the severity of melasma were analysed using the Kruskal-Wallis test. Results Of the total of 30 patients enrolled in the study, the majority were in the age group of 36-45 (average of 44) years and work as housewives. The highest risk factor was sun exposure. The melasma pattern was dominated by centrofacial patterns, majority of melasma types were epidermal, and the most severe degree was moderate. A moderate negative correlation between BDNF levels and the duration of melasma was found (p=0.007; r= -0.485). There was no significant relationship between BDNF levels and the severity of melasma (p=0.387). Conclusion No significant relationship between BDNF levels and the severity of melasma indicates that the causes of melasma are multifactorial, such as sun exposure, genetic, hormonal, and other factors (drugs, neural and psychological, and lipid metabolism).

Anxiety Disorder and BDNF: Integrative Review of the Literature

Objective: To analyze the relationship between Brain-Derived Neurotrophic Factor (BDNF) and Anxiety Disorders (AD) and describe possible damage to the psychic functions in individuals with this disorder. Methods: this was an integrative review of the literature of articles published between 2008 and 2018, selected in the bibliographic databases of PubMed, Scielo and LILACS. Results and Discussion: In total, 28 articles were selected, of studies conducted with humans and animals. The relationship between levels of BDNF, including polymorphism in the BDNF gene, and AD was observed to have been approached, showing that the neurotrophic hypothesis could contribute to the physiopathology of ADs, including volumetric changes in regions of the brain, comprising psychic functions in patients with AD. Furthermore, studies have shown that the BDNF levels may reflect the effect of antidepressant or neuromodulation therapy, and that exposure to stressful factors may be related to individuals with this genetic variant being more vulnerable to developing AD. Conclusions: The data obtained in this research pointed towards an inverse relationship between BDNF levels and AD, and to the contribution of the neurotrophic hypothesis to the neurobiology of these disturbances, including damage to the psychic functions. Whereas considering that other studies to not show this relationship, further studies need to be conducted to validate a possible association. It was possible to hypothesize that BDNF, although unspecific, could be a biomarker associated with AD, and could be capable of helping with preventive actions to maintain mental health.

BDNF and Cognitive Function in Chilean Schizophrenic Patients

Despite cognitive symptoms being very important in schizophrenia, not every schizophrenic patient has a significant cognitive deficit. The molecular mechanisms underlying the different degrees of cognitive functioning in schizophrenic patients are not sufficiently understood. We studied the relation between brain-derived neurotrophic factor (BDNF) and cognitive functioning in two groups of schizophrenic patients with different cognitive statuses. According to the Montreal Cognitive Assessment (MoCA) results, the schizophrenic patients were classified into two subgroups: normal cognition (26 or more) and cognitive deficit (25 or less). We measured their plasma BDNF levels using ELISAs. The statistical analyses were performed using Spearman’s Rho and Kruskal–Wallis tests. We found a statistically significant positive correlation between the plasma BDNF levels and MoCA score (p = 0.04) in the subgroup of schizophrenic patients with a cognitive deficit (n = 29). However, this correlation was not observed in the patients with normal cognition (n = 11) and was not observed in the total patient group (n = 40). These results support a significant role for BDNF in the cognitive functioning of schizophrenics with some degree of cognitive deficit, but suggest that BDNF may not be crucial in patients with a normal cognitive status. These findings provide information about the molecular basis underlying cognitive deficits in this illness.

Negative relationship between brain-derived neurotrophic factor (BDNF) and attention: A possible elevation in BDNF level among high-altitude migrants.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic family that plays a vital role in regulating neuronal activity and synaptic plasticity in the brain, affects attention. However, studies investigating the association between BDNF and attention in long-term high-altitude (HA) migrants are limited in the literature. As HA affects both BDNF and attention, the relationship between these factors becomes more complex. Therefore, this study aimed to evaluate the relationship between peripheral blood concentrations of BDNF and the three attentional networks in both behavioral and electrical aspects of the brain in long-term HA migrants. Ninety-eight Han adults (mean age: 34.74 ± 3.48 years, 51 females and 47 males, all have lived at Lhasa for 11.30 ± 3.82 years) were recruited in this study. For all participants, the serum BDNF levels were assessed using enzyme-linked immunosorbent assay; event-related potentials (N1, P1, and P3) were recorded during the Attentional Networks Test, which was used as the measure of three attentional networks. Executive control scores were negatively correlated with P3 amplitude (r = -0.20, p = 0.044), and serum BDNF levels were positively correlated with executive control scores (r = 0.24, p = 0.019) and negatively correlated with P3 amplitude (r = -0.22, p = 0.027). Through grouping of BDNF levels and three attentional networks, executive control was found to be significantly higher in the high BDNF group than in the low BDNF group (p = 0.010). Different BDNF levels were associated with both orienting scores (χ2 = 6.99, p = 0.030) and executive control scores (χ2 = 9.03, p = 0.011). The higher the BDNF level, the worse was the executive function and the lower was the average P3 amplitude and vice versa. Females were found to have higher alerting scores than males (p = 0.023). This study presented the relationship between BDNF and attention under HA. The higher the BDNF level, the worse was the executive control, suggesting that after long-term exposure to HA, hypoxia injury of the brain may occur in individuals with relatively higher BDNF levels, and this higher BDNF level may be the result of self-rehabilitation tackling the adverse effects brought by the HA environment.

Brain-derived neurotrophic factor associated with kidney function

BackgroundWe examined the relationship between brain-derived neurotrophic factor (BDNF) and chronic kidney disease (CKD).MethodsFirst, a cross-sectional study was conducted in 480 participants without known diabetes. An oral glucose tolerance test (OGTT) was administered after overnight fasting, and blood samples were collected at 0, 30, and 120 min. Second, a total of 3003 participants were enrolled for the case–control genetic analysis. After assigning them to a case or a control group based on age and CKD status, we investigated the association between BDNF gene variants and susceptibility to CKD.ResultsA higher fasting serum BDNF quartile was significantly associated with a lower prevalence of CKD (P value for trend < 0.001). Based on the receiver operating characteristic analysis, the fasting BDNF level had a larger area under the curve for differentiating CKD (0.645, 95% CI 0.583‒0.707) than the BDNF levels at both 30 min (0.547, 95% CI 0.481‒0.612) and 120 min (0.598, 95% CI 0.536‒0.661). A significantly lower CKD prevalence (odds ratio = 0.30, 95% CI 0.12‒0.71) was observed in the highest quartile of fasting BDNF level than that in the lowest quartile, whereas no interquartile differences were observed for BDNF levels determined at 30 or 120 min during the OGTT. Furthermore, BDNF-associated variants, including rs12098908, rs12577517, and rs72891405, were significantly associated with CKD.ConclusionsThe BDNF level at fasting, but not at 30 and 120 min after glucose intake, was an independent indicator of CKD. In addition, significant associations were observed between three BDNF gene variants and CKD.

The Association between Brain-Derived Neurotrophic Factor (BDNF) Protein Level and Body Mass Index.

Background and Objectives: Obesity is a major health concern worldwide. Many studies emphasize the important role of brain-derived neurotrophic factor (BDNF) in regulating appetite and body weight. We aimed to investigate the association between BDNF protein serum levels and body mass index (BMI). Materials and Methods: We conducted a cross-sectional study among 108 healthy adult participants divided into six categories depending on their body mass index (BMI). The ages of the participants ranged between 21 to 45 years. The BDNF serum level was measured using the enzyme-linked immunosorbent assay (ELISA) technique. Results: A Kruskal-Wallis test showed a significant difference in BDNF between the different BMI categories, χ2(2) = 24.201, p &lt; 0.001. Our data also showed that BDNF levels were significantly lower in people with obesity classes II and III than those of normal weight (p &lt; 0.05). The Spearman rank correlation test was statistically significant with negative correlations between the BMI and BDNF (r) = -0.478, (p &lt; 0.01). Moreover, we observed a negative dose-dependent relationship pattern between BMI categories and the levels of circulating BDNF protein. Conclusions: In this study, our data support the hypothesis that low serum levels of BDNF are associated with high BMI and obesity in Saudi adults.

Depression, anxiety, and sleep quality in childhood onset systemic lupus erythematosus and relationship with brain-derived neurotrophic factor.

The association between brain-derived neurotrophic factor (BDNF) and systemic lupus erythematosus (SLE) is controversial, and no study investigated the clinical associations of BDNF in patients with childhood onset systemic lupus erythematosus (cSLE). In this study, we aimed to investigate the serum levels of BDNF in patients with cSLE and examine whether a relationship of BDNF exists among depression, anxiety, and sleep quality. Thirty patients and age-sex matched healthy controls were included. Depression, anxiety, sleep quality and quality of life were assessed by relevant questionnaires. Disease activity was assessed according to the SLE disease activity index (SLEDAI) and serum BDNF level was measured by the enzyme-linked immunosorbent assay method. Serum BDNF level was significantly lower in cSLE patients than healthy controls (21981 vs 29905 pg/mL, p = 0.001) and significantly decreased level was observed in active cSLE (SLEDAI >0), then those with SLEDAI = 0 (17110 vs 26852 pg/mL, p = 0.005). Although the scores of the depression, anxiety, sleep quality and quality of life questionnaires were strongly correlated with each other, no correlation was observed with serum BDNF levels. In patients with cSLE, serum level of BDNF was significantly decreased compared to healthy controls. Our results suggest that serum BDNF levels were not associated with the presence of anxiety, depression and poor sleep quality and might be dictated by the pathophysiological process of SLE rather than mood disorders.

Relationship between serum levels of BDNF and HDL-cholesterol in women with metabolic syndrome

Background and Aims : Recently, a link between brain-derived neurotrophic factor (BDNF), glucose and lipid metabolism, inflammation and cardiovascular disease has been suggested. The aim of our study was to investigate the relationship between serum levels of BDNF and HDL-C in women with metabolic syndrome.

Interactions Among Brain-Derived Neurotrophic Factor and Neuroimmune Pathways Are Key Components of the Major Psychiatric Disorders.

The purpose of this review is to summarize the current knowledge regarding the reciprocal associations between brain-derived neurotrophic factor (BDNF) and immune-inflammatory pathways and how these links may explain the involvement of this neurotrophin in the immune pathophysiology of mood disorders and schizophrenia. Toward this end, we delineated the protein-protein interaction (PPI) network centered around BDNF and searched PubMed, Scopus, Google Scholar, and Science Direct for papers dealing with the involvement of BDNF in the major psychosis, neurodevelopment, neuronal functions, and immune-inflammatory and related pathways. The PPI network was built based on the significant interactions of BDNF with neurotrophic (NTRK2, NTF4, and NGFR), immune (cytokines, STAT3, TRAF6), and cell-cell junction (CTNNB, CDH1) DEPs (differentially expressed proteins). Enrichment analysis shows that the most significant terms associated with this PPI network are the tyrosine kinase receptor (TRKR) and Src homology region two domain-containing phosphatase-2 (SHP2) pathways, tyrosine kinase receptor signaling pathways, positive regulation of kinase and transferase activity, cytokine signaling, and negative regulation of the immune response. The participation of BDNF in the immune response and its interactions with neuroprotective and cell-cell adhesion DEPs is probably a conserved regulatory process which protects against the many detrimental effects of immune activation and hyperinflammation including neurotoxicity. Lowered BDNF levels in mood disorders and schizophrenia (a) are associated with disruptions in neurotrophic signaling and activated immune-inflammatory pathways leading to neurotoxicity and (b) may interact with the reduced expression of other DEPs (CTNNB1, CDH1, or DISC1) leading to multiple aberrations in synapse and axonal functions.

Exploring the association between brain-derived neurotrophic factor (BDNF) levels and longitudinal psychopathological and cognitive changes in Sardinian psychotic patients

IntroductionSchizophrenia spectrum disorders are among the most debilitating mental disorders and evidence on its pathophysiological underpinnings is scant. The brain-derived neurotrophic factor (BDNF) appears to be involved in the pathophysiology of these complex psychiatric disorders.ObjectivesThe present study investigates the longitudinal variation of serum BDNF levels in a 24-month observational cohort study of Sardinian psychotic patients (LABSP). This study assessed the variation in BDNF serum levels and its relationship with psychopathological and cognitive changes. Further, we also examined if genetic variations within the BDNF gene could moderate these relationships.MethodsEvery six months 105 LABSP patients were assessed for their BDNF serum levels, as well as for a series of psychopathological, cognitive, and drug-related measures. Four tag single nucleotide polymorphisms (SNPs) within the BDNF gene were selected and analyzed using Polymerase Chain Reaction (PCR). Longitudinal data were analyzed using mixed-effects linear regression models (MLRM).ResultsAnalysis showed significantly lower peripheral BDNF levels in psychotic patients with depressive and negative symptoms. BDNF levels were also decreased in patients scoring lower in cognitive measures such as symbol coding and semantic fluency. In addition, Val66Met polymorphism within the BDNF gene significantly moderated the relationship between the severity of negative symptoms and BDNF levels.ConclusionsOur findings are consistent with previous literature suggesting that peripheral BDNF levels are associated with some cognitive domains and mood disruption in major psychosis. The results also suggest the lack of association between most BDNF genetic variants, except Val66Met polymorphism, with the severity of negative symptoms.DisclosureNo significant relationships.

Association of peripheral manifestation of brain-derived neurotrophic factor with depression: A meta-analysis.

BackgroundThe relationship between brain‐derived neurotrophic factor (BDNF) and depression is a hot topic in research as several results of preclinical and clinical studies have shown controversial results. Our meta‐analysis aims to evaluate and update the current status of peripheral BDNF with depression.MethodsWe performed a meta‐analysis by comprehensively searching PubMed and Web of Science for English‐language literature from inception to 1st of June 2020. The search terms included brain‐derived neurotrophic factor or BDNF in combination with depression, without year restriction. Using STATA software, data were pooled using a random‐effects model.ResultsIn our literature search, 24 studies involving 1130 depressed patients and 1378 healthy individuals met our inclusion criteria. The results of our meta‐analysis showed that the peripheral levels of BDNF levels significantly decreased in depression than nondepressed healthy controls (SMD = −0.89, 95% CI = −1.41, −0.38, p < .0001); however, the significant heterogeneity among studies (Q = 740.91, I 2 = 96.8; p < .001) was discovered. Trim‐and‐fill estimations for the adjustment of publication bias indicated that publication bias had no impact on our results. Our sub‐group analysis showed that a history of depression and alcohol consumption had an effect on the level of BDNF. In addition, age and gender did not affect the heterogeneity of BDNF in the meta‐analysis.ConclusionsAlthough decreased peripheral expression of BDNF certainly presents a risk of depression, we cannot find a definite relationship between the peripheral level of BDNF with depression to use BDNF as a reliable biomarker to assess the depression in clinical practice. We propose that future research should consider all the factors affecting BDNF and assess the level of proBDNF and mBDNF separately while evaluating the patients with depression objectively.

Stress‐Induced Gut Dysmotility is Associated with Altered Intestinal BDNF‐TrkB Signaling

IntroductionWhile stress is associated with incidence of gut dysmotility disorders, mechanisms by which stress causes dysmotility are not well understood. In the central nervous system (CNS), stress causes behavioral deficits by increasing the levels of Glucocorticoid hormone to suppress molecular signaling between brain‐derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB). We hypothesize that stress causes a Glucocorticoid‐mediated reduction in BDNF‐TrkB signaling in the enteric nervous system (ENS), whose neurons, which modulate diverse gut functions, reside entirely within the gut wall.MethodsGut motility was assayed by analyzing the whole gut transit time (WGTT) of an orally gavaged carmine red dye in adult mice. Effect of stress was tested by comparing WGTT of Stress‐Induced Dysmotility (SID) mice, wherein age‐matched adult male mice were restrained for one hour, with that of unrestrained control mice. The effect of Glucocorticoids was tested by comparing WGTT of age‐matched adult C57/BL6 male mice dosed with Dexamethasone (DEX, a Glucocorticoid receptor agonist, intra‐peritoneal 5mg/kg), with that of saline‐dosed control mice. Effect of DEX on enteric BDNF levels (using R&amp;D ELISA kit) was tested by using total proteins isolated from preparations of adult murine longitudinal muscle‐myenteric plexus (LM‐MP) tissues cultured with and without DEX (1 µM) for 4 hours. TrkB exists in full‐length and truncated (TrkB.T1) isoforms, and the presence of TrkB.T1 in ENS neurons was observed by immunofluorescence analyses of ENS tissue of TrkB.T1‐V5 transgenic mice. Involvement of TrkB.T1 isoform in SID was tested by comparing WGTT of male transgenic mice containing partial (T1‐Het) or complete loss (T1 KO) of TrkB.T1. Differences were compared for statistical significance using Student’s t‐test and Mann‐Whitney test.Results5 consecutive days of 1 hour restraint caused a significant delay in WGTT of adult C57/BL6 SID mice, when compared to controls (Table 1). DEX caused a significant delay in WGTT, when compared to control mice (Table 1). DEX treatment caused a significant reduction in BDNF levels (Table 1). TrkB.T1‐V5 mice show presence of TrkB.T1 on adult enteric neurons (Fig 1). A single hour of restraint caused a significant delay in WGTT in adult T1 KO mice, when compared with littermate T1 Het mice (Table 1).DiscussionRestraint stress and DEX caused similar delay in gut transit in wildtype mice, and since DEX decreased gut BDNF levels, we infer that stress‐induced increase in glucocorticoid signaling delayed gut transit by suppressing enteric BDNF levels. Increased susceptibility of T1 KO mice to SID highlights the important role of the truncated TrkB.T1 receptor in maintenance of normal gut motility during acute and moderate stress. Thus, our data implicates altered BDNF‐TrkB.T1 signaling in the etiology of Stress Induced Dysmotility.

Serum BDNF and cognitive dysfunction in SLE: findings from a cohort of 111 patients

The association between brain-derived neurotrophic factor (BDNF) and neuropsychiatric systemic lupus erythematosus (NPSLE) is controversial in the literature. Cognitive dysfunction (CD) is a common, underdiagnosed NPSLE manifestation, but its pathophysiology is unknown. Thus, we investigate serum BDNF as a potential biomarker of CD in a cohort of SLE patients. We included 63 SLE patients, 48 NPSLE, and 57 age- and gender-matched controls (CON). All participants underwent neuropsychological assessment. Data on cardiovascular comorbidities, SLE disease activity index (SLEDAI), and Systemic Lupus International Collaborating Clinics damage index (SLICC-DI) were compiled. Multiple regression analyses evaluated predictors of serum BDNF levels. Serum BDNF levels were lower in SLE and NPSLE patients than in CON (SLE 800.4 ± 502.7 vs. NPSLE 779.7 ± 426.3 vs. CON 1,345.5ng/mL ± 438.4; p < 0.001). In addition, hypertension (B: - 192.5, SE: 84.3, 95% CI: - 359.7 to - 25.3, p = 0.024) and SLICC-DI score (B: - 75.9, SE: 27.2, 95% CI: - 129.8 to - 22, p = 0.006) were predictors of serum BDNF levels in SLE. There was no relation between BDNF levels and CD. BDNF levels are lower in SLE patients than CON and inversely associated with hypertension and SLICC-DI scores. No association between BDNF levels and CD or NPSLE was observed in this cohort. These findings indicate that BDNF may be associated with overall burden in SLE rather than specific manifestations such as cognition impairment. Key Points • BDNF is associated with an overall burden in SLE rather than specific manifestations such as cognition dysfunction. • BDNF levels are reduced in patients with SLE, and higher SLICC-DI scores and hypertension are independent predictors of lower serum BDNF levels. • The cognitive dysfunction rate is elevated (46%) among Brazilian SLE patients.

Brain-Derived Neurotrophic Factor as a Clinical Biomarker in Predicting the Development of Post-Stroke Depression: A Review of Evidence.

Studying the relationship between brain-derived neurotrophic factor (BDNF) and post-stroke depression (PSD) may help determine the potential for depression in stroke patients at the earliest stage possible. Current research has identified changes in BDNF levels in PSD patients. Thus, this article was intended as a review of evidence with respect to changes in the expression of BDNF in patients with PSD by integrating extant findings.We conducted a search in the electronic databases PubMed, EMBASE, and PsycINFO (all records from January 1, 2000, through October 20, 2020) using keywords: “brain-derived neurotrophic factor OR BDNF,” “post-stroke depression OR PSD,” “expression level,” “association,” and “relationship.” Returned articles were considered for inclusion in this review if they were empirical studies investigating the association between BDNF expression and PSD.Seven original papers were selected for review and revealed inconsistent findings. Five out of seven studies reported a significant decrease in BDNF levels in PSD patients at a certain stage (most likely the early stage) of stroke after admission, whereas the other two showed contrasting findings.Overall, this review reveals associations between changes in serum BDNF levels and depression following stroke. Whether serum BDNF levels, especially in the early phase of stroke, can be a potentially effective biomarker for predicting the risk of subsequent PSD development is still open to debate.