Difference In Brain-derived Neurotrophic Factor Levels Research Articles

Brain-derived neurotrophic factor serum levels as a candidate biomarker for withdrawal in crack heroin dependence

BackgroundCrack heroin is a novel opiate derivative with highly addictive properties and unfamiliar health consequences. It causes a variety of brain dysfunctions that are mediated by neurochemical alterations and abnormal neuroplasticity. Brain-derived neurotrophic factor (BDNF) is a widely recognized biological marker implicated in the neuropathology of substance use during substance use disorder and withdrawal. Its involvement can significantly contribute to the severity of withdrawal symptoms. Hence, this study aimed to evaluate BDNF levels in crack heroin users before and after withdrawal.MethodsIn this cross-sectional study, 148 male participants were recruited and divided into two groups: persons with crack heroin use disorder (n = 74) and the controls (n = 74). The BDNF serum levels were measured in both crack heroin users and control groups upon hospitalization and again after twenty-one days of withdrawal using the enzyme-linked immunosorbent assay.ResultsThe results demonstrated that BDNF levels in persons with crack heroin use disorder upon admission were significantly lower than the levels observed upon discharge and in the control group (p < 0.05). Additionally, a significant difference in BDNF levels was found between persons with crack heroin use disorder at admission and discharge (p = 0.038). Furthermore, BDNF levels showed an inverse correlation with the daily dose of substance use (r= -0.420, p = 0.03) and the duration of crack heroin use (r= -0.235, p = 0.001).ConclusionsA progressive increment in BDNF levels during early detoxification is associated with the daily amount of substance use and the duration of substance use. Our findings suggest that changes in BDNF serum levels during crack heroin use disorder and withdrawal could serve as potential biomarkers for assessing the intensity of withdrawal symptoms and substance use-related behaviors.

The Effect of Exercise Volume on Depressive-Related Behaviors and Levels of Brain-Derived Neurotrophic Factor and Serum Testosterone Levels

Objective: The aim of the present study was to investigate the effect of training volume on depression-related behaviors and serum levels of brain-derived neurotrophic factor (BDNF) and testosterone in mice. Male NMRI mice, approximately 80 days old and weighing 20 to 23 grams, were used in this study. Methods and Materials: They were kept under a 12-hour light/12-hour dark cycle at a temperature of 23±1°C, with adequate food and water provided. The male NMRI mice, approximately 80 days old and weighing 20 to 23 grams, were kept under a 12-hour light/12-hour dark cycle at a temperature of 23±1°C, with adequate food and water provided. From 90 days old to 118 days old, the animals underwent swimming exercise for 4 weeks. They were divided into two groups: long-term training volume and short-term training volume. The short-term swimming group included one session of short-term training, while the long-term group included three sessions of long-term training with 10-minute swimming periods and 15-minute rest intervals between each session. The water depth and swimming duration gradually increased from 5 to 15 centimeters (second to fourth week) and from 20 (second to third week) to 30 (fourth week) minutes per day. The non-exercised animals were placed in a round tank without water for a duration similar to that of the exercised animals. Results: The results showed a significant difference in immobility duration between the control group and the two training groups, as well as between the two training groups (P ≤ 0.05). There was also a significant difference in depression levels between the two training groups and between the long-term training group and the control group (P ≤ 0.05). However, there was no significant difference between the short-term training group and the control group (P ≥ 0.05). Post hoc test results indicated a significant difference in BDNF levels between the control group and the long-term training group (P ≤ 0.05). Furthermore, there was a significant difference in testosterone levels between the control group and both the short-term and long-term training groups (P ≤ 0.05), but no difference between the two training groups (P ≥ 0.05). Conclusion: Based on the overall results of the study, different training volumes have varying effects on depression and BDNF levels, with long-term training producing greater effects.

Levels of ADAM10 and BDNF in low‐educated healthy older adults and individuals with Alzheimer’s dementia

AbstractBackgroundAlzheimer’s Disease (AD) is the most common type of dementia among older adults (Prince et al., 2015). Research has focused on specific biomarkers for AD that could contribute to early diagnosis. Levels of ADAM10, for example, are altered in people with AD, and this protein has been studied as a potential blood‐based biomarker for this disease (Elsworthy et al., 2022). Brain‐derived neurotrophic factor (BDNF), in turn, is a protective factor involved, for example, in neurotransmitter modulation, as well as in neuronal plasticity and survival (Tarassova et al., 2020). Therefore, analyzing the possible relationship between these variables is relevant to expand the knowledge of AD biomarkers.Aimto verify whether there is a relationship between the levels of ADAM10 and BDNF among healthy older adults and individuals with AD with low educational attainment.MethodsThis is a cross‐sectional study in which community‐dwelling older adults with low educational levels (n = 85) were assigned to two groups: healthy older adults (n = 37) and participants with AD (n = 48). The interview was based on a sociodemographic questionnaire and cognitive assessment (Mini‐Mental State Examination‐MMSE and the Clock Drawing Test‐CDT). Participants had their blood collected, and SDS‐PAGE and Western Blotting techniques were used to measure plasma ADAM10 levels.ResultsParticipants with AD were older (p&lt;.001); had less educational attainment (p&lt;.001); worse performance on MMSE (p&lt;.001), and on its domains [Orientation (p&lt;.001), attention, memory (p = .028), language(p&lt;.001), and evocation(p&lt;.001)]; as well as worse performance on CDT (p&lt;.001). Also, compared to the healthy group, persons with AD had significantly higher levels of plasma ADAM10 (p = .04). No difference in BDNF levels was observed between the groups (p = .07). Correlation analyses revealed a significant correlation between ADAM10 and years of education (r = ‐.234; p = .04); MMSE total score (r = ‐.328; p = .003), and its orientation (r = ‐.224; p = .04), attention (r = ‐.278; p = .01), and evocation (r = ‐.332; p = .003) domains. BNDF was not correlated with any of the variables in this study.ConclusionThis study showed that plasma ADAM10 levels in low‐educated older adults, but not BDNF, differ between healthy and AD participants. Our results reinforce the potential role of ADAM10 as a biomarker for AD.

A study of serum brain-derived neurotrophic factor level in individuals with obsessive compulsive disorder and their first-degree relatives as compared to the healthy population.

The nosological tradition in psychiatry defines diagnostic criteria for disorders based on expert consensus than objective biological markers reflecting underlying neurobiological correlates. Endophenotypes have been researched as heritable biological markers that can be quantified and defined to represent intermediate measures of a psychiatric illness. In obsessive-compulsive disorder (OCD), various putative biomarkers such as neuropsychological, neurophysiological, neuroradiological, brain-derived neurotrophic factor (BDNF), etc., have been explored. The study aimed to compare levels of serum BDNF in individuals with OCD and their unaffected first-degree relatives (FDR) with healthy controls (HC). This cross-sectional study compared serum BDNF levels in medication-free/naive individuals with OCD (n = 30) to their FDR (n = 30) and age-sex matched HC (n = 30). Intergroup comparison was done using analysis of variance (ANOVA) and post-hoc Tukey's test. Correlation analysis was conducted to find the relationship of sociodemographic and clinical correlates to serum BDNF as well as dimensional subtypes of OCD. No significant difference in BDNF levels was observed between OCD and HC (P = 0.13) but a significantly higher level was found in the FDR group compared to age-sex matched HC (P = 0.02). BDNF levels may have a complex interplay influencing the genetic inheritance and clinical manifestations of OCD. Further research is required before considering it a viable biomarker.

A meta-analysis on the role of brain-derived neurotrophic factor in Parkinson's disease patients.

Brain-derived neurotrophic factor (BDNF) is essential for the development of dopaminergic neurons in the substantia nigra. To investigate the level of BDNF among Parkinson's disease (PD) subjects and the influence of depression on BDNF levels. A total of 1920 subjects were included in the analysis; of these, 1034 had PD and 886 were healthy controls. A thorough literature search up to May 2022 was conducted. The mean difference (MD) of BDNF levels and 95% confidence intervals (95% CIs) were calculated with random or fixed effects models. Compared to healthy controls, levels of BDNF were significantly lower in patients with PD (MD = -1.60, 95% CI (-2.49, -0.70), p < 0.001). Patients with PD and depression had significantly lower levels of BDNF (MD = -3.39, 95% CI (-5.55, -1.23), p = 0.002), as well as those with PD without depression (MD = -0.80, 95% CI (-1.56, -0.03), p = 0.04). However, there was no discernible change in BDNF levels (MD = -0.82, 95% CI (1.75, 0.10), p = 0.08) between the participants with PD and depression compared to the PD patients alone. Compared with healthy controls, BDNF levels were significantly lower in the subjects with PD combined with depression, and PD without depression. However, there was no discernible difference in BDNF levels between subjects with PD with depression compared to those with PD without depression.

Association of plasma BDNF levels with different stages of Alzheimer’s disease: a cross-sectional study

ABSTRACT Background Growing evidence shows that the expression of brain-derived neurotrophic factor (BDNF) is altered in the peripheral blood of participants with Alzheimer’s disease (AD). It is unclear, however, whether altered BDNF expression is also observed in the early stages of AD. Methods In the present study, 138 normal controls (NC), 57 participants with subjective cognitive decline (SCD), and 37 participants with amnestic mild cognitive impairment (aMCI) and AD were included. Plasma BDNF protein levels were assessed using a commercial multiplex Luminex-based kit. Patient samples were also probed for the presence of BDNF gene variant rs6265. Results Pairwise comparisons between the groups showed that there was not a significant difference in BDNF levels when comparing SCD with NC and when comparing SCD with aMCI/AD, but BDNF levels in aMCI/AD samples were increased when compared with NC samples. For models differentiating clinical groups, discriminant analysis was performed by including education, APOE genotype, and BDNF levels in the model. This approach distinguishes participants with SCD (AUC = 0.630) and aMCI/AD (AUC = 0.665) from NC. Conclusion Our results suggest that expression of BDNF in plasma is altered at the clinical stage of AD.

Serum Brain-Derived Neurotrophic Factor (BDNF) in COVID-19 Patients and its Association with the COVID-19 Manifestations.

COVID-19 is a systematic disease that frequently implies neurological and non-neurological manifestations, predominantly by inducing hypoxia. Brain-derived neurotrophic factor (BDNF) is a key factor in regulating functions of nervous and respiratory systems and has been strongly related to hypoxia. Therefore, this study planned to investigate BDNF association with the COVID-19 manifestations especially neurological impairments and the infection-induced hypoxia. We enrolled sixty-four COVID-19 patients and twenty-four healthy individuals in this study. Patients were divided into two groups, with and without neurological manifestations, and their serum BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA). COVID-19 patients had significantly lower BDNF levels than healthy individuals (p = 0.023). BDNF levels were significantly lower in patients with neurological manifestations compared to healthy individuals (p = 0.010). However, we did not observe a statistically significant difference in BDNF levels between patients with and without neurological manifestations (p = 0.175). BDNF’s levels were significantly lower in patients with CNS manifestations (p = 0.039) and higher in patients with fever (p = 0.03) and dyspnea (p = 0.006). Secondly, BDNF levels have a significant negative association with oxygen therapy requirement (p = 0.015). These results strongly suggest the critical association between dysregulated BDNF and hypoxia in promoting COVID-19 manifestations, particularly neurological impairments. Supplementary InformationThe online version contains supplementary material available at 10.1007/s12031-022-02039-1.

Levels of brain-derived neurotrophic factor in patients with multiple sclerosis.

ObjectiveTo determine the levels of brain‐derived neurotrophic factor (BDNF) in the serum of patients suffering from multiple sclerosis (MS) to evaluate the potential of serum BDNF as a biomarker for MS.MethodsUsing a recently validated enzyme‐linked immunoassay (ELISA) we measured BDNF in patients with MS (pwMS), diagnosed according to the 2001 McDonald criteria and aged between 18 and 70 years, participating in a long‐term cohort study with annual clinical visits, including blood sampling, neuropsychological testing, and brain magnetic resonance imaging (MRI). The results were compared with an age‐ and sex‐matched cohort of healthy controls (HC). Correlations between BDNF levels and a range of clinical and magnetic resonance imaging variables were assessed using an adjusted linear model.ResultsIn total, 259 pwMS and 259 HC were included, with a mean age of 44.42 ± 11.06 and 44.31 ± 11.26 years respectively. Eleven had a clinically isolated syndrome (CIS), 178 relapsing remitting MS (RRMS), 56 secondary progressive MS (SPMS), and 14 primary progressive MS (PPMS). Compared with controls, mean BDNF levels were lower by 8 % (p˂0.001) in pwMS. The level of BDNF in patients with SPMS was lower than in RRMS (p = 0.004).InterpretationWe conclude that while the use of comparatively large cohorts enables the detection of a significant difference in BDNF levels between pwMS and HC, the difference is small and unlikely to usefully inform decision‐making processes at an individual patient level.

The effect of interferon-β therapy on brain-derived neurotrophic factor serum concentration in relapsing— remitting multiple sclerosis: a randomized clinical trial

Introduction: Beta interferon (IFN-β) is known as the first-line therapy in relapsing-remitting multiple sclerosis (RRMS). Recent studies have shown different effects of IFN-β on brain-derived neurotrophic factor (BDNF) serum levels. Given the known role of BDNF in the restoration and conservation of the nervous system, this study was designed to investigate the possible effect of this drug through stimulating BDNF production. Objectives: Impressible treatments for progressive multiple sclerosis (MS) are still being sought. Individual response to existing treatments for MS varies significantly among patients while the risk of serious adverse events remains an issue, especially for the novel drugs. Patients and Methods: In this clinical trial, 96 patients newly diagnosed with RRMS were studied within three months, in 3 groups of 32 subjects. Each group received one of the foregoing drugs (Avonex, Rebif and Betaferon). BDNF levels were compared between different groups at the end. Results: BDNF serum concentration in all groups was significantly different (P&lt;0.001) compared to baseline after 3 months. And comparison between groups showed a significant difference between the groups receiving Betaferon (IFN-β1b) (P=0.001) and Rebif (P=0.002) compared to the other groups. Avonex compared with either control or Betaferon (IFN-β1b) and Rebif groups showed no significant difference. Also the correlation between the mean changes in expanded disability status scale (EDSS) and BDNF was not observed (r = -0.189, P=0.065). Conclusions: Significant difference in BDNF levels were observed between groups.

The relationship of Chlamydophila pneumoniae with schizophrenia: The role of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in this relationship

Several pathogens have been suspected of playing a role in the pathogenesis of schizophrenia. Chronic inflammation has been proposed to occur as a result of persistent infection caused by Chlamydophila pneumoniae cells that reside in brain endothelial cells for many years. It was recently hypothesized that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) may play prominent roles in the development of schizophrenia. NT-3 and BDNF levels have been suggested to change in response to various manifestations of infection. Therefore, we aimed to elucidate the roles of BDNF and NT3 in the schizophrenia–C. pneumoniae infection relationship. RT-PCR, immunofluorescence and ELISA methods were used. Fifty patients suffering from schizophrenia and 35 healthy individuals were included as the patient group (PG) and the healthy control group (HCG), respectively. We detected persistent infection in 14 of the 50 individuals in the PG and in 1 of the 35 individuals in the HCG. A significant difference was found between the two groups (p<0.05). Twenty-two individuals in the PG and 13 in the HCG showed seropositivity for past C. pneumoniae infection, and no difference was observed between the groups (p>0.05). C. pneumoniae DNA was not detected in any group. A significant difference in NT-3 levels was observed between the groups, with very low levels in the PG (p<0.001). A significant difference in BDNF levels was also found, with lower levels in the PG (p<0.05). The mean serum NT-3 level was higher in the PG cases with C. pneumoniae seropositivity than in seronegative cases; however, this difference was not statistically significant (p>0.05). In conclusion, we suggest that NT-3 levels during persistent C. pneumoniae infection may play a role in this relationship.

Childhood atopic dermatitis-Brain-derived neurotrophic factor correlates with serum eosinophil cationic protein and disease severity.

Several studies have shown that neurotrophins including brain-derived neurotrophic factor (BDNF) play a role in chronic inflammatory skin diseases such as atopic dermatitis (AD). BDNF is increased in the serum samples of adults with AD. Interestingly, eosinophils of these patients can release and produce BDNF. We analyzed BDNF serum levels with ELISA and their correlation with SCORAD score, eosinophil cationic protein (ECP), total IgE, IL-4, IL-13 and IL-31 in children with AD (n = 56) compared to nonatopic healthy children (n = 25). In addition, we analyzed FLG loss-of-function mutations in 17 children with AD and their connection to BDNF. BDNF serum levels were significantly higher in children with AD. Further, BDNF correlated with disease activity, serum ECP, and total IgE serum levels in AD. There was no difference in BDNF levels of filaggrin-positive or filaggrin-negative children with AD, and there was no correlation of BDNF with IL-31 and Th2 cytokines including IL-4 and IL-13. Together, our data add new insights into the pathophysiology of AD, suggesting that serum BDNF which correlates with disease severity contributes to the regulation of inflammation in an eosinophil-, but not Th2-dependent manner.

Female gender and gastrointestinal symptoms, not brain-derived neurotrophic factor, are associated with depression and anxiety in cirrhosis.

Cirrhosis places a substantial burden on the psychological status of affected individuals. The aim of our study was to identify the associated factors of psychological distress in cirrhosis. A total of 208 patients with cirrhosis were recruited. Each patient received validated questionnaires to assess gastrointestinal (GI) symptoms, depression, and anxiety. Serum brain-derived neurotrophic factor (BDNF) levels were measured by enzyme-linked immunosorbent assay. A total of 16.35% of patients (n = 34) were diagnosed with depression and 10.58% (n = 22) with anxiety. The percentages of female patients among those diagnosed with depression and anxiety were 58.8% and 77.3%, respectively, which were significantly higher than that in non-depressed (35.1%) and non-anxious patients (34.4%). The patients who showed more GI symptoms had higher depression and anxiety scores. The GI symptom scores of patients with depression and anxiety were 4 (2.75, 7) and 4 (2.75, 7.25), respectively, which were significantly higher than that of patients without depression (2 [0, 4]) and anxiety (2 [1, 4]). Significantly higher depression and anxiety scores were detected in patients who suffered from abdominal bloating, belching, anorexia, abdominal pain, nausea/vomiting, and constipation. Cirrhotic patients had higher serum levels of BDNF than healthy controls (159.33 [96.64, 243.30]pg/mL vs. 70.74 [56.58, 93.52]pg/mL). In the cirrhosis group, there was no significant difference in BDNF levels between depressed and non-depressed patients. Multiple linear regression analysis revealed that depression and anxiety were each independently associated with female gender and GI symptom scores. Female gender and GI symptoms are closely associated with depression and anxiety in cirrhosis. There is no significant correlation between BDNF level and psychological distress in cirrhosis.

Correlation Between Use of Agomelatine and Bdnf Levels in the Treatment of Depressive Disorders

Introduction Agomelatine is a novel antidepressant whose role in the treatment of depression is growing. Brain-derived neurotrophic factor (BDNF) is a neurotrophin, acting on synaptic plasticity and maintaining midbrain dopaminergic and cholinergic neurons. Patients with depressive disorders exhibit diminished plasma BDNF levels, usually increased by antidepressant treatment. Objectives Aim of the study was to investigate the effects produced by chronic agomelatine treatment on BDNF serum levels in depressed patients. Methods 27 depressed patients and 29 healthy controls (HC) were enrolled in the study. Clinical assessment was performed at T0, T1 (after 2 weeks) and T2 (after 8 weeks). After screening period, patients were administered agomelatine (25 mg/day, per os); in the case of no clinical response, the dosage could be increased to 50 mg/day, At T0 and T2, venous blood samples were collected. Results Mann-Whitney U-test was performed to compare baseline BDNF levels between patients and HC. Baseline BDNF levels were found to be significantly lower in depressed individuals. During the study period, Friedman's test showed significant changes in BDNF serum levels. Their increase was correlated with depressive symptoms, as measured by reduction in HDRS scores. Also, responders showed a significant difference in BDNF levels after 2-week agomelatine treatment, while non-responders showed no difference. Conclusions our study demonstrates that patients affected by Depressive Disorders show an increase in BDNF serum concentration after a two-weeks therapy with agomelatine, with the clinical improvement of depression, anhedonia and anxiety significantly correlated with the levels of the neurotrophin.

Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients.

Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case-control designs. The aim of this study was to investigate whether BDNF and NT-3 levels differ between patients with rapid cycling bipolar disorder and healthy control subjects and whether BDNF and NT-3 levels alter with affective states in rapid cycling bipolar disorder patients. Plasma levels of BDNF and NT-3 were measured in 37 rapid cycling bipolar disorder patients and in 40 age- and gender matched healthy control subjects using enzyme-linked immunosorbent assay (ELISA). In a longitudinal design, repeated measurements of BDNF and NT-3 were evaluated in various affective states in bipolar disorder patients during a 6-12 months period and compared with repeated measurements in healthy control subjects. Careful attention was given to standardization of all procedures and adjustment for potential confounders of BDNF and NT-3. In linear mixed models, adjusting for demographical and lifestyle factors, levels of BDNF were significantly elevated in bipolar disorder patients in euthymic- (p<0.05), depressed- (p<0.005) and manic/hypomanic (p<0.005) states compared with healthy control subjects. Within bipolar disorder patients, adjusting for medication, there was no significant difference in BDNF levels between affective states, with equally elevated levels present in euthymic-, depressive- and manic/hypomanic patients. Levels of BDNF were higher in patients with longer duration of illness compared with patients with shorter duration of illness. We found no difference in NT-3 levels between bipolar disorder patients in any affective state compared with healthy control subjects and no difference in NT-3 levels between affective states in bipolar disorder patients. The results suggest that BDNF may be a marker related to illness stage in bipolar disorder, not varying with affective states in rapid cycling bipolar disorder patients. Due to the nature of comparison, it cannot be excluded that the finding of elevated BDNF levels in bipolar disorder patients compared with healthy controls could be influenced by medication.

Brain-derived neurotrophic factor blood levels are decreased in schizophrenia patients and associate with rs6265 genotypes

ObjectivesA growing number of studies implicate brain-derived neurotrophic factor (BDNF), an important promoter of synaptic transmission and neural plasticity, in the pathogenesis of schizophrenia. However, the existing data are controversial, that may reflect population differences between studied groups. Design and methodsIn the present study we performed a comparative analysis of BDNF plasma levels and its relation with rs6265 (G196A; Val66Met) polymorphism of BDNF gene (BDNF) in schizophrenia-affected and healthy subjects (controls) of the Armenian population. To check the influence of antipsychotics on BDNF plasma levels both medicated and non-medicated patients were involved in this study. Patients with paranoid form of schizophrenia chronically treated with typical antipsychotics (n=103), age- and sex-matched controls (n=105), and 25 antipsychotic-naive first-episode schizophrenia patients were involved. The levels of BDNF in the blood plasma were measured with a solid-phase enzyme-linked immunosorbent assay. ResultsDecreased plasma levels of BDNF in both medicated and non-medicated schizophrenia patients compared to controls were observed. No significant difference in BDNF levels between medicated and non-medicated patients was detected. It was also detected that, compared to individuals homozygous for the standard allele (G/G) of rs6265, carriers of the rs6265 minor allele (A/G+A/A), which is significantly more frequent in schizophrenia patients than in controls, had decreased BDNF levels. ConclusionsThe data obtained suggested that the pathogenesis of schizophrenia is characterized by genetically predetermined decreased blood levels of BDNF. These results indicated that genetically determined alterations of neuroimmune modulators may be among the risk factors of schizophrenia and contribute to disease-specific pathologic changes in functional activity of both the neuronal synaptic plasticity and the immune system.

Serum BDNF Levels in Relation to Illness Severity, Suicide Attempts, and Central Serotonin Activity in Patients with Major Depressive Disorder: A Pilot Study

The aim of this study was to test the hypothesis that serum levels of brain-derived neurotrophic factor (BDNF) are correlated with the loudness dependence of auditory evoked potentials (LDAEP). The question of whether there is a difference in BDNF levels between depressive patients according to their illness severity, history of suicide attempts, and central serotonin activity was also addressed. A sample of 51 patients who met the criteria for major depressive disorder following diagnosis using axis I of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders – text revision comprised the study subjects. The patients were stratified into two subgroups based on their illness severity, history of suicide attempts, and their LDAEP values. The LDAEP was evaluated by measuring the auditory event-related potentials, and serum BDNF was measured using blood sampling before beginning medication with serotonergic agents. There was no difference in serum BDNF levels between the two patient subgroups. The subgroup with moderate-to-severe depression (n = 16) was reanalyzed after stratifying it into two subgroups according to LDAEP and BDNF values (dichotomized at the medians into low and high). The high-LDAEP subgroup had higher serum BDNF levels and total Barratt Impulsiveness Scale score than the low-LDAEP subgroup (p = 0.03 and 0.036, respectively). Serum BDNF levels were positively correlated with LDAEP and total Beck Hopelessness Scale (BHS) score (r = 0.56, p = 0.025, and r = 0.59, p = 0.016, respectively). The high-BDNF subgroup had a higher LDAEP and total BHS score than the low-BDNF subgroup (p = 0.046 and p = 0.011, respectively). This is the first study to demonstrate a relationship between the BDNF level and LDAEP in Asian depressive patients. Intriguingly, the high-BDNF subgroup (divided according to illness severity) exhibited a more severe psychopathology on some psychometric rating scales, a finding that conflicts with previous results.

Sex Differences in Stress Reactivity of Hippocampal BDNF in Mice are Associated with the Female Preponderance of Decreased Locomotor Activity in Response to Restraint Stress

The incidence and prevalence of depression is higher in women than in men, but the cause of this sex discrepancy remains unknown. Brain-derived neurotrophic factor (BDNF) is a key protein for maintaining neuronal integrity. The purpose of this study was to investigate the female preponderance in behavioral responsivity to restraint stress focusing on the stress reactivity of BDNF in the hippocampus. Male and female ICR mice were exposed to a 3-h session of restraint stress. Plasma corticosterone was measured by high-performance liquid chromatography. BDNF mRNA expression in the whole hippocampus was measured by quantitative real-time reverse transcription-polymerase chain reaction. Wheel-running activity was monitored during the dark period. In response to restraint stress, the increase in levels of serum corticosterone was higher in female than in male mice. Restraint stress resulted in decreased voluntary wheel-running behavior that was greater in female than male animals. In addition to these sex differences in stress reactivity, we found a significant sex difference in BDNF levels in the hippocampus of restraint-stressed mice; total BDNF levels significantly decreased in female mice, but not in male mice in response to the stress. Furthermore, BDNF exon I and IV mRNA expression also showed the same tendency. These data indicate that the reduction in levels of voluntary wheel-running activity in response to stress can be significantly influenced by sex. Moreover, our findings suggest a link between the sex differences in this behavioral response to stress and differential stress reactivity in the production of BDNF in the hippocampus.

Effects of Physical Exercise on Plasma Levels of Brain-Derived Neurotrophic Factor and Depressive Symptoms in Elderly Women—A Randomized Clinical Trial

ObjectivesTo investigate the effect of 2 standardized exercise programs, muscle strength exercises (SE) and aerobic exercises (AE), on the plasma levels of brain-derived neurotrophic factor (BDNF) and depressive symptoms in 451 elderly women. DesignA randomized controlled trial. SettingBelo Horizonte/MG–Brazil. ParticipantsCommunity-dwelling older women (N=451; age, 65–89y). InterventionThe participants were divided into 2 groups: SE and AE. Both protocols lasted 10 weeks, and 30 sessions (1-h sessions) in total were performed 3 times a week under the direct supervision of physical therapists. Main Outcome MeasuresPlasma levels of BDNF (enzyme-linked immunosorbent assay) and depressive symptoms (Geriatric Depression Scale). ResultsThere was a significant difference for BDNF plasma levels between the SE and AE groups (P=.009). Post hoc analysis revealed a pre-post intervention difference in BDNF levels only for the SE group (P=.008). A statistically significant difference was found for the pre- and postintervention Geriatric Depression Scale scores in both groups (P=.001), showing that the effects of both exercise protocols were comparable regarding depressive symptoms (P=.185). ConclusionsThe present findings have demonstrated the positive effect of muscle strengthening and aerobic intervention on depressive symptoms in community-dwelling elderly women. Interestingly, only SE significantly increased the plasma levels of BDNF in our sample. The positive effects of physical exercise on depressive symptoms in the elderly were not mediated by BDNF.

Val66Met polymorphism and BDNF levels in Alzheimer's disease patients in North Indian population

Analysis of serum brain-derived neurotrophic factor (BDNF) levels in Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI) and controls with BDNF gene polymorphism and cognitive function were investigated. The study recruited 63 AD patients, 15 aMCI and 63 age- and sex-matched healthy controls from All India Institute of Medical Sciences, New Delhi, India. Patients with AD (12268.3 ± 7099.9 pg BDNF/ml) and aMCI (10780 ± 4184.2 pg BDNF/ml) had higher serum levels than had the controls (9362.833 ± 5883.32 pg BDNF/ml). Significant difference in BDNF levels was not found between the three groups. No significant difference was obtained between BDNF genotype and allele distribution between AD patients, aMCI versus controls; genotypic frequency: Chi-square = 3.21; p-value = 0.20 and allelic frequency: Chi-square = 0.412, p-value = 0.521, df = 1 (AD vs controls); Chi-square = 1.63, p-value = 0.201, df = 1 (aMCI vs controls). In conclusion, val66met polymorphism and BDNF serum level between the three groups and genotype did not significantly affect the serum BDNF level or age, Mini-Mental State Examination score in AD and aMCI. Further studies are necessary to elucidate the kinetics and the potential role of serum BDNF as a marker of disease progression in AD patients.

Flavonoids of puerarin versus tanshinone ⅡA for ischemic stroke: a randomized controlled trial

Flavonoids are widely used today in the treatment of ischemic stroke. The therapeutic effects and functions of flavonoids are, therefore, generating more and more interest. To investigate the therapeutic effects and functions of flavonoids of puerarin in treating patients with ischemic stroke. A total of 67 inpatients suffering from ischemic stroke from the Department of Neurology, Changhai Hospital in China were divided into two groups randomly, the treatment group, which was treated with flavonoids of puerarin, and the control group, administered with tanshinone II A sulfate instead. Defects in neurological function were evaluated according to the National Institutes of Health Stroke Scale (NIHSS) on the first day of onset. Lactate dehydrogenase (LDH), serum interleukin-6 (IL-6) and brain-derived neurotrophic factor (BDNF) levels were determined by radioimmunoassay on the second trial day. After a 14-day treatment, LDH, serum IL-6 and BDNF levels and NIHSS score were also detected, and CT perfusion imaging was used to measure and analyze the regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and mean transit time (MTT). On the first day, NIHSS scores of the two groups were similar. On the second day there was no significant difference in LDH and IL-6 levels between the treatment group and the control group. After a 14-day treatment, LDH and IL-6 levels and the NIHSS score in the treatment group were lower than those in the control group (P<0.05). There was no significant difference in BDNF levels in the two groups. After 14 d, the CT perfusion imaging demonstrated that the treatment group showed more effective blood perfusion than the control group. Flavonoids of puerarin can restrain the increase of IL-6 after acute ischemic stroke, and depress the LDH raised by reperfusion after cerebral ischemia. It can also enhance blood perfusion of the ischemic region.