Between Brain-derived Neurotrophic Factor Research Articles

Association between Brain-derived Neurotrophic Factor (BDNF) Val66Met polymorphism and Clinical Outcomes as Measured with PANSS Scale in Patients With Schizophrenia in Two Psychiatric Centres in East Java – Indonesia

Aim: The etiology of schizophrenia has been linked to complex interactions of genetic and environmental factors, and among them are genes that regulate BDNF (Brain-derived Neurotrophic Factor) expression. The BDNF has been linked to the pathophysiology of schizophrenia, particularly the Val66Met polymorphism. This study aims to assess BDNF Val66Met polymorphism and its role in positive and negative symptoms in patients with schizophrenia in East Java. Subjects and Methods: A total of 52 subjects with schizophrenia living in East Java were assessed for BDNF Val66Met polymorphism. The analysis was performed using Statistical the Social Sciences (SPSS) software version 22. Clinical assessment was conducted using the positive and negative syndrome scale (PANSS). Data were analyzed using linear regression multivariate analysis. Results: Our study found that Val/Met polymorphism is associated negatively with the total PANSS scores (beta coefficient = -12.299, p = 0.017). The Val/Val polymorphism is associated with negative symptoms (beta coefficient = 22.607, p = 0.043). The present study’s findings considered age, gender, education level, number of antipsychotics consumed, medication adherence, and duration of untreated psychosis. Conclusion: Val/Val polymorphism is associated with a higher PANSS total score. Val/Met genotype is associated with more severe positive symptoms, while the Val/Val genotype is associated with more negative symptoms. Further study with a larger and multicenter sample is needed to clarify further the relationship of BDNF polymorphism to clinical outcomes of schizophrenia.

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.

Role of KCC2 in the Regulation of Brain-Derived Neurotrophic Factor on Ethanol Consumption in Rats.

Alcohol use disorder (AUD) is a common and complex disorder resulting from repetitive alcohol drinking. The mesocorticolimbic dopamine (DA) system, originating from the ventral tegmental area (VTA) in the midbrain, is involved in the rewarding effect of ethanol. The γ-aminobutyric acid (GABA) neurons in VTA appear to be key substrates of acute and chronic ethanol, which regulates DA neurotransmission indirectly in the mesocorticolimbic system. Despite significant research on the relationship between brain-derived neurotrophic factor (BDNF) and reduced alcohol consumption in male rats involving tropomyosin-related kinase B (TrkB), the mechanisms of BDNF-TrkB regulating alcohol behavior remain scarce. K+-Cl- cotransporter 2 (KCC2) plays a crucial role in synaptic function in GABAergic neurons by modulating intracellular chlorine homeostasis. Here, we found that 4-week intermittent alcohol exposure impaired the function of KCC2 in VTA, evidenced by a lower expression level of phosphorylated KCC2 and decreased ratio of phosphorylated KCC2 to total KCC2, especially 72h after withdrawal from 4-week ethanol exposure in male rats. CLP290 (a KCC2 activator) reduced excessive alcohol consumption after alcohol withdrawal, whereas VU0240551 (a specific KCC2 inhibitor) further enhanced alcohol intake. Importantly, VU0240551 reversed the attenuating effects of BDNF and 7,8-dihydroxyflavone (7,8-DHF) on alcohol consumption after withdrawal. Moreover, intraperitoneal injection of 7,8-DHF upregulated KCC2 expression and phosphorylated KCC2 in VTA 72h after withdrawal from ethanol exposure in male rats. Collectively, our data indicate that KCC2 may be critical in the regulating action of BDNF-TrkB on ethanol consumption in AUD.

Epigenetic alteration of BDNF gene, social and health status as predictors of food and nutrition insecurity among familiar coffee farmers

Introduction: state of Food and Nutritional Security (FNS) is one that should guarantee the right of permanent access to quality food and in sufficient quantity without prejudicing access to other basic rights. In Brazil, rural family farming establishments represent 84.4% of total agricultural establishments and contribute to more than 70% of all food consumed by Brazilians. In this context, the production of the coffee commodity stands out. However, despite being food producers, they do not earn a good income. Slow economic activity can lead to loss of wages and income, illness, as well as food insecurity (FNiS). In addition, the molecular effects of FNiS are poorly studied, especially epigenetic. Objective: the objective of the present study is to analyze the association between Brain-Derived Neurotrophic Factor (BDNF) DNA methylation and socio demographic, lifestyle, and epigenetic factors, among coffee farmers in the Caparaó zone, in Espirito Santo, Southeast Brazil. Methods: the study was carried out in 22 randomly selected coffee producing communities in Zona Caparaó, an area that produces coffee of recognized quality. A total of 570 coffee farming households, 18 to 60 years of age, were included in the study by answering a questionnaire about socioeconomic characteristics, land use and ownership, behavior, health, and working conditions. FNiS evaluation was carried out using the Brazilian Food Insecurity Scale. BDNF exon I methylation was examined by methylation-specific PCR. Body mass index and biochemical analyses were performed. Logistic regression models were used to verify factors associated with FNiS (p&lt;0.05). Data were analyzed using the Stata® statistical software package version 14. Results: the FNiS prevalence found was 23.68%. In multivariable logistic regression, the occurrence of FNiS was associated with hypermethylation of exon I of the BDNF promoter exon I [ORa = 5.03 (95% (1.98, 12.82)] when compared to the unmethylated gene. Moreover, FNiS was associated with excessive workload [ORa = 3.36 (1.23, 9.22)], possession of less land (hectares) [ORa = 0.77 (0.67, 0.90)] and greater number symptoms and / or illnesses in real life [ORa = 1.12 (1.04.1.20)]. Conclusion: there is a high prevalence of Food Insecurity in the studied region. This phenomenon was associated with epigenetic factors (BDNF methylation), excessive workload, small land ownership and a greater number of diseases / symptoms. Food insecurity is a psychosocial stressor that can lead to epigenetic changes in the BDNF gene, responsible for regulating cognitive functions, neuronal survival and involved in the genesis of psychiatric diseases.

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.

Exploration of the Moderating Effects of Physical Activity and Early Life Stress on the Relation between Brain-Derived Neurotrophic Factor (BDNF) rs6265 Variants and Depressive Symptoms among Adolescents.

Depression affects one in five persons at 18 years of age. Allele A of the brain-derived neurotrophic factor (BDNF) rs6265 is considered to be a risk factor for depression. Previous studies of the interaction between BDNF rs6265, early adversity, and/or physical activity have shown mixed results. In this study, we explored the relation between BDNF rs6265 polymorphism and childhood stress, as well as the moderating effect of physical activity in relation to depressive symptoms using binary logistic regressions and process models 1, 2 and 3 applied to data obtained at three times (waves 1, 2 and 3) from the Survey of Adolescent Life in Västmanland cohort study (SALVe). Results revealed that both childhood stress and physical activity had a moderation effect; physical activity in wave 1 with an R2 change = 0.006, p = 0.013, and the Johnson–Neyman regions of significance (RoS) below 1.259, p = 0.05 for 11.97%; childhood stress in wave 2 with the R2 change = 0.008, p = 0 002, and RoS below 1.561 with 26.71% and >4.515 with 18.20%; and a three-way interaction in wave 1 in genotype AA carriers. These results suggest that allele A is susceptible to physical activity (positive environment) and childhood stress (negative environment).

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.