Peripheral Brain-derived Neurotrophic Factor Research Articles

No evidence for altered plasma NGF and BDNF levels in fibromyalgia patients

There has been a surging interest in the putative role of peripheral growth factors in the pathophysiology of fibromyalgia, specifically in the peripheral sensitization that occurs in chronic pain disorders. This cross-sectional study set out to assess and compare brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in plasma samples from fibromyalgia patients and healthy controls. Plasma BDNF and NGF were measured in 89 fibromyalgia patients and 36 pain-free controls, and compared using ANCOVA controlling for potential confounders, as well as Bayesian methods for parameter estimation and model evaluation. BDNF and NGF levels in fibromyalgia patients did not differ from those in pain-free controls. Statistical methods were consistent, with both frequentist and Bayesian approaches leading to the same conclusions. Our study fails to replicate the finding that peripheral BDNF is altered in fibromyalgia, and instead our findings suggest that plasma levels of growth factor appear normative in fibromyalgia.

Carbohydrate-restricted Diet and Exercise Increase Brain-derived Neurotrophic Factor and Cognitive Function: A Randomized Crossover Trial.

IntroductionMetabolic syndrome (MetS) has been recognized as one of the most important clinical challenges and global health issues of today. Growing evidence suggests that mechanisms of energy metabolism may also play a key role in mediating aspects of cognitive function. Brain-derived neurotrophic factor (BDNF) is one such factor well known for its critical role in neuronal plasticity, including memory and learning, and more recently metabolic processes. BDNF levels have been shown separately to be dependent on diet and exercise programming.PurposeThe purpose of this study was to investigate the effect of diet and exercise on BDNF levels and cognitive functioning with any metabolic association in individuals characterized with MetS.MethodsTwelve subjects with MetS followed a randomized crossover design with two four-week interventions, including a carbohydrate (CHO)-restricted Paleolithic-based diet (CRPD; <50gCHO) with sedentary activity (CRPD-Sed) and CRPD with high intensity interval training (HIIT; CRPD-Sed), separated by a four-week washout period. The HIIT exercise consisted of 10 x 60 s cycling intervals interspersed with 60 s of active recovery 3 day/week for four-week. Serum BDNF was detected and quantified via enzyme-linked immunosorbent assay (ELISA). Cognitive executive function (Stroop Test) and self-perceived cognitive symptoms and function (MOS-CFS) were quantified. A two-way analysis of variance with repeated measures was performed with post-hoc analysis using simple effects analysis with a Bonferroni adjustment. The level of statistical significance was established a priori as P < 0.05.ResultsCompared to baseline, CRPD-Sed and CRPD-Ex improved variables for cognitive function, including increased peripheral serum BDNF levels (20% and 38%), psychomotor speed and cognitive flexibility (-14%, -14%), and self-perceived cognitive symptoms and functioning (+8%, +16%), respectively. BDNF inversely correlated with %body fat (r = -0.35, P < 0.05), fasting glucose (r = -0.64, P < 0.05), triglycerides (r = -0.55, P < 0.05), and insulin sensitivity (r = -0.25, P < 0.05).ConclusionThis study shows the short-term beneficial effects of carbohydrate-restricted diet on serum BDNF and executive function in those individuals characterized with MetS. We have shown that the addition of exercise can further improve neuroprotection and cognitive function beyond the results of diet alone.

Peripheral Brain-Derived Neurotrophic Factor and Contactin-1 Levels in Patients with Attention-Deficit/Hyperactivity Disorder.

Brain-derived neurotrophic factor (BDNF) facilitates neuronal growth and plasticity, and is crucial for learning and memory. Contactin-1 (CNTN1) is a member of the subfamily of neural immunoglobulin and is involved in the formation of axon connections in the developing nervous system. This cross-sectional study investigates whether BDNF and CNTN1 affect susceptibility to attention deficit/hyperactivity disorder (ADHD). A total of 136 drug-naïve patients with ADHD (108 boys and 28 girls) and 71 healthy controls (45 boys and 26 girls) were recruited. Blood samples were obtained to measure the plasma levels of BDNF and CNTN1 in each child. We found that BDNF levels in the ADHD boys exceeded those in the control boys, but BDNF levels in the ADHD girls were lower than those in the control girls. Boys who had higher BDNF levels performed worse on the Wechsler Intelligence Scale for Children—Fourth Edition, but girls who had higher BDNF levels made fewer omission errors in the Conners’ Continuous Performance Test. However, CNTN1 level did not differ significantly between patients and controls, and were not correlated to ADHD characteristics, regardless of gender. The findings suggest BDNF may influence sex-specific susceptibility to ADHD, but CNTN1 was not associated with ADHD pathophysiology.

Peripheral brain-derived neurotrophic factor contributes to chronic osteoarthritis joint pain.

Brain-derived neurotrophic factor (BDNF) and the high-affinity receptor tropomyosin receptor kinase B (TrkB) have important roles in neuronal survival and in spinal sensitization mechanisms associated with chronic pain. Recent clinical evidence also supports a peripheral role of BDNF in osteoarthritis (OA), with synovial expression of TrkB associated with higher OA pain. The aim of this study was to use clinical samples and animal models to explore the potential contribution of knee joint BDNF/TrkB signalling to chronic OA pain. Brain-derived neurotrophic factor and TrkB mRNA and protein were present in knee synovia from OA patients (16 women, 14 men, median age 67 years [interquartile range: 61-73]). There was a significant positive correlation between mRNA expression of NTRK2 (TrkB) and the proinflammatory chemokine fractalkine in the OA synovia. Using the surgical medial meniscal transection (MNX) model and the chemical monosodium iodoacetate (MIA) model of OA pain in male rats, the effects of peripheral BDNF injection, vs sequestering endogenous BDNF with TrkB-Fc chimera, on established pain behaviour were determined. Intra-articular injection of BDNF augmented established OA pain behaviour in MIA rats, but had no effect in controls. Intra-articular injection of the TrkB-Fc chimera acutely reversed pain behaviour to a similar extent in both models of OA pain (weight-bearing asymmetry MIA: -11 ± 4%, MNX: -12 ± 4%), compared to vehicle treatment. Our data suggesting a contribution of peripheral knee joint BDNF/TrkB signalling in the maintenance of chronic OA joint pain support further investigation of the therapeutic potential of this target.

The Impact of Different Types of Exercise Training on Peripheral Blood Brain-Derived Neurotrophic Factor Concentrations in Older Adults: A Meta-Analysis.

As the prevalence of neurodegenerative diseases (such as dementia) continues to increase due to population aging, it is mandatory to understand the role of exercise for maintaining/improving brain health. To analyse the impact of aerobic, strength and combined aerobic/strength exercise training on peripheral brain-derived neurotrophic factor (BDNF) concentrations in older adults (minimum age 60years). This meta-analysis adhered to PRISMA guidelines. Inclusion criteria were: (i) studies with subjects aged ≥ 60years, (ii) completing a single exercise bout or an exercise programme, with (iii) measurements of blood BDNF in the periphery; (iv) with comparison between (a) an intervention and control group or (b) two intervention groups, or (c) pre- and post-measurements of an exercise intervention without control group. Studies with specific interest in known chronic co-morbidities or brain diseases affecting the peripheral and/or central nervous system, except for dementia, were excluded. In general, peripheral blood BDNF concentrations increased significantly after a single aerobic/strength exercise bout (Z = 2.21, P = 0.03) as well as after an exercise programme (Z = 4.72, P < 0.001). However, when comparing the different types of exercise within these programmes, the increase in the peripheral BDNF concentrations was significant after strength training (Z = 2.94, P = 0.003) and combined aerobic/strength training (Z = 3.03, P = 0.002) but not after (low-to-moderate intense) aerobic exercise training (Z = 0.82, P = 0.41). Based on current evidence, to increase the peripheral blood BDNF concentrations in older adults, strength training and combined aerobic/strength training is effective. More studies are needed to examine the impact of aerobic exercise training.

Associations Between Circulating Basal BDNF, IGF-1 and Physical Fitness

Exercise-induced increase in circulating insulin-like growth factor 1 (IGF-1) levels might stimulate brain-derived neurotrophic factor (BDNF) expression. Thus, circulating IGF-1 can travel from the periphery to the brain and there stimulate the expression of BDNF and facilitate long-lasting changes in neural activity. It has been shown that chronic training leads to upregulation of basal levels of both BDNF and IGF-1. Several longitudinal studies have also shown that aerobic exercise acutely elevates circulating BDNF levels in humans. PURPOSE: To investigate associations of peripheral BDNF and IGF-1 with several physical fitness components at rest. METHODS: 792 adults (26±6 yr) men participated. BDNF and IGF-1 concentrations were analyzed from venous blood samples using an ELISA Assay (Human BDNF ELISA kit, ScienCell Research laboratories, San Diego, California) and Dynex DS 2 ELISA processing system (Dynex Technologies, Chantilly, Virginia). Cardiorespiratory fitness (VO2max) was determined using an indirect graded cycle ergometer test until exhaustion. Bilateral maximal isometric leg (MVCleg) and arm extension forces (MVCarm) were measured using dynamometers. Muscular endurance tests consisted of repeated 1-min push-ups and sit-ups, while standing long jump assessed muscular power. RESULTS: The mean±SD BDNF and IGF-1 concentrations were 15.20±3.96 ng/ml, 25.0±6.9nmol/l, respectively, while VO2max was 41.1±8.8ml/kg/min, MVCleg 3394±933N, MVCarm 871±216N, push-ups 28±14reps/min, sit-ups 35±12reps/min, standing long jump 227±26cm. BDNF and IGF-1 correlated weakly with each other (r=-0.146, p=0.003). Linear regression analysis (adjusted for age, smoking and education) revealed that associations between BDNF and physical fitness were weak for VO2max (β=-0.077, p=0.006) and muscle fitness (β=-0.077, p=0.895). This was also the case for IGF-1. CONCLUSIONS: The associations between peripheral BDNF, IGF-1 and physical fitness components were weak or non-existent at rest in the present cross-sectional design. Thus, it seems that only exercise-induced elevated values of BDNF and IGF-1 may associate with each other and physical fitness components. Therefore, their interactions should be investigated in future studies during acute and / or chronic exercises.

Increased plasma Brain-Derived Neurotrophic Factor (BDNF) levels in females with schizophrenia

Brain-Derived Neurotrophic Factor (BDNF) acts as a critical regulator of synaptogenesis and synaptic plasticity. Sex differences have been demonstrated in many aspects of schizophrenia. This study tested for sex-specific differences in peripheral BDNF levels in people with schizophrenia and healthy controls. We measured circulating plasma BDNF levels in 95 people with schizophrenia and 80 healthy controls. Plasma BDNF levels were significantly elevated in females with schizophrenia compared to males with schizophrenia and to female healthy controls. These results suggest that sex differences in peripheral BDNF levels may contribute to other sex related differences in schizophrenia.

Functional remediation improves bipolar disorder functioning with no effects on brain-derived neurotrophic factor levels

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

Acute psychosocial stress increases serum BDNF levels: an antagonistic relation to cortisol but no group differences after mental training.

Brain-derived neurotrophic factor (BDNF) is an essential facilitator of neuronal plasticity. By counteracting the adverse effects of excessive stress-induced glucocorticoid signaling, BDNF has been implicated as a resilience factor to psychopathology caused by chronic stress. Insights into the effects of acute stress on peripheral BDNF levels in humans are inconclusive. The short-term interplay between BDNF and cortisol in response to acute psychosocial stress remains unexplored. Furthermore, it is unknown whether mental training that is effective at reducing cortisol reactivity can also influence BDNF during acute stress. In the current study, we investigated serum BDNF levels during an acute psychosocial stress paradigm, the Trier Social Stress Test (TSST), in 301 healthy participants (178 women, mean age = 40.65) recruited as part of the ReSource Project, a large-scale mental training study consisting of three distinct 3-month training modules. Using a cross-sectional study design, we first examined the relationship between BDNF and salivary cortisol in a control group with no mental training. Subsequent analyses focused on differences in BDNF stress levels between control and mental training groups. We show that serum BDNF is indeed stress-sensitive, characterized by a significant post-stress increase and subsequent decline to recovery. While respective increases in BDNF and cortisol were not associated, we found two indications for an antagonistic relationship. Higher BDNF peaks after stress were associated with steeper cortisol recovery. On the other hand, the magnitude of the cortisol stress response was linked to steeper BDNF recovery after stress. BDNF levels were not modulated by any of the mental training modules. Providing novel evidence for the dynamics of BDNF and cortisol during acute stress, our findings may further inform research on the physiological mechanisms involved in stress chronification and the associated health risks.

Longitudinal multi-level biomarker analysis of BDNF in major depression and bipolar disorder.

Preliminary evidence suggests that BDNF (brain derived neurotrophic factor) rs6265 genetic polymorphism, BDNF gene promotor methylation and BDNF serum levels might play an important role in the pathogenesis of affective disorders. As studies testing the BDNF system across molecular levels are sparse, this study aimed at investigating the BDNF val66met genotype, BDNF DNA methylation changes and peripheral BDNF serum levels in acute and remitted phases of MDD (major depressive disorder) and BD (bipolar disorder) and healthy controls. We found a significant difference of methylation levels at CpG site 1-1-1 and 3-1-1 between MDD and healthy controls (p < 0.003) with MDD patients showing significantly higher methylation levels. CpG 5-2-1 revealed a statistically significant difference between MDD and healthy controls and MDD and BD (p = 0.00003). Similar to the results of the methylation analysis a significant difference between MDD and healthy controls was found in BDNF serum levels (p = 0.002) with significantly lower BDNF serum levels in MDD compared to healthy controls. A difference between the samples from admission and discharge from hospital of both BDNF gene methylation and serum levels could not be detected in the present study and no influence of the BDNF val66met genotype on neither methylation nor BDNF serum level.

Effects of Elastic Resistance Training on Functional Performance and Myokines in Older Women—A Randomized Controlled Trial

ObjectivesTo investigate the short- and long-term effects of elastic resistance training (ERT) on physical performance, inflammatory markers, and myokines in older women living in a nursing home. DesignA randomized controlled trial, with 12 weeks of ERT intervention. Setting and participantsNursing home. Twenty female nursing home residents (mean age = 84 ± 8 years) were randomized into 2 groups: the training group (n = 11), and the control group (n = 9). MeasuresMuscle mass was estimated with bioelectrical impedance, and the functional test Short Physical Performance Battery (SPPB) was performed, whereas handgrip strength and plasma concentration of myokines and inflammatory markers were measured before and after the intervention period. Additional blood samples were also taken after the fourth ERT session. A mixed model (group × time) analysis of variance was applied to determine the effect on primary and secondary outcomes. ResultsAfter 1 exercise session, the training group showed a significant increase in brain-derived neurotrophic factor (BDNF) (P = .04) and a decrease in interleukin (IL)-8 (P = .01) plasma concentration. After 12 weeks of intervention, the results showed a significant group × time effects for the SPPB total score (P < .01), as well as gait speed (P = .04), chair rise (P < .01), and BDNF concentration (P = .02). However, there were no significant interactions for grip strength, IL-15, IL-8, resistin, glucose, and C-reactive protein (P ≥ .06). Conclusions/ImplicationsThe present study emphasizes the clinical impact of moderate-intensity ERT on mobility and functional performance in older women. The results indicate that an increase in exercise-induced peripheral BDNF may have a protective role in the preservation of muscular function in older women. Incorporating ERT into nursing homes could be a feasible preventive strategy to counteract functional deterioration.

Myelinating Proteins in MS Are Linked to Volumetric Brain MRI Changes.

There is evidence of a relationship between promyelinating proteins and clinical multiple sclerosis (MS) activity during clinical relapse or recovery from clinical relapses. We examined the linkage between promyelinating biomarkers and volumetric changes in MS subjects during serial magnetic resonance imaging (MRI). We enrolled 13 MS subjects with active brain MRI scans not on disease modifying therapies. Subjects underwent baseline MRI, serum, and cerebrospinal fluid (CSF) sampling. Qualitative changes, new/resolving gadolinium, new/enlarging/diminishing T2 and T1 hypointense lesions, were compared to baseline in subsequent MRI scans, and volumetric analysis was calculated. Analysis of biomarkers on serial CSF samples was performed only in subjects with qualitative (and quantitative) changes on MRI. The study was performed at a MS Center of Excellence academic medical center. There was increased CSF neural cell adhesion molecule (N-CAM) during increased qualitative T1 activity. A positive correlation between CSF and serum N-CAM and T1 lesion volume was observed. A negative correlation between serum brain-derived neurotrophic factor (BDNF) and BPH (T1 vol/T2 vol + T1 vol) was observed. Increased N-CAM levels may be related to repair or remyelination following injury to the brain as shown by increased T1 volumes. Our data suggest an early kind of blood signaling that induces release of peripheral BDNF levels.

Decreased Serum Brain-Derived Neurotrophic Factor (BDNF) Levels in Patients with Alzheimer's Disease (AD): A Systematic Review and Meta-Analysis.

Findings from previous studies reporting the levels of serum brain-derived neurotrophic factor (BDNF) in patients with Alzheimer’s disease (AD) and individuals with mild cognitive impairment (MCI) have been conflicting. Hence, we performed a meta-analysis to examine the aggregate levels of serum BDNF in patients with AD and individuals with MCI, in comparison with healthy controls. Fifteen studies were included for the comparison between AD and healthy control (HC) (n = 2067). Serum BDNF levels were significantly lower in patients with AD (SMD: −0.282; 95% confidence interval [CI]: −0.535 to −0.028; significant heterogeneity: I2 = 83.962). Meta-regression identified age (p < 0.001) and MMSE scores (p < 0.001) to be the significant moderators that could explain the heterogeneity in findings in these studies. Additionally, there were no significant differences in serum BDNF levels between patients with AD and MCI (eight studies, n = 906) and between MCI and HC (nine studies, n = 5090). In all, patients with AD, but not MCI, have significantly lower serum BDNF levels compared to healthy controls. This meta-analysis confirmed the direction of change in serum BDNF levels in dementia. This finding suggests that a significant change in peripheral BDNF levels can only be detected at the late stage of the dementia spectrum. Molecular mechanisms, implications on interventional trials, and future directions for studies examining BDNF in dementia were discussed.

Roles of myokines in exercise-induced improvement of neuropsychiatric function.

Exercise is a well-known non-pharmacological intervention to improve brain functions, including cognition, memory, and motor coordination. Contraction of skeletal muscles during exercise releases humoral factors that regulate the whole-body metabolism via interaction with other non-muscle organs. Myokines are muscle-derived effectors that regulate body metabolism by autocrine, paracrine, or endocrine action and were reportedly suggested as "exercise factors" that can improve the brain function. However, several aspects remain to be elucidated, namely the specific activities of myokines related to the whole-body metabolism or brain function, the mechanisms of regulation of other organs or cells, the sources of "exercise factors" that regulate brain function, and their mechanisms of interaction with non-muscle organs. In this paper, we present the physiological functions of myokines secreted by exercise, including regulation of the whole-body metabolism by interaction with other organs and adaptation of skeletal muscles to exercise. In addition, we discuss the functions of myokines that possibly contribute to exercise-induced improvement of brain function. Among several myokines, brain-derived neurotrophic factor (BDNF) is the most studied myokine that regulates adult neurogenesis and synaptic plasticity. However, the source of circulating BDNF and its upstream effector, insulin-like growth factor (IGF-1), and irisin and the effect size of peripheral BDNF, irisin, and IGF-1 released after exercise should be further investigated. Recently, cathepsin B has been reported to be secreted from skeletal muscles and upregulate BDNF following exercise, which was associated with improved cognitive function. We reviewed the level of evidence for the effect of myokine on the brain function. Level of evidence for the association of the change in circulating myokine following exercise and improvement of neuropsychiatric function is lower than the level of evidence for the benefit of exercise on the brain. Therefore, more clinical evidences for the association of myokine release after exercise and their effect on the brain function are required. Finally, we discuss the effect size of the action of myokines on cognitive benefits of exercise, in addition to other contributors, such as improvement of the cardiovascular system or the effect of "exercise factors" released from non-muscle organs, particularly in patients with sarcopenia.

Association between cognition and peripheral brain-derived neurotrophic factor in a sample of normal adults in Kano, Nigeria

Introduction: Cognition is an important physiological and social element for both humans and animals. There is paucity of literature on cognitive function in Africans. Furthermore, the molecular mechanisms involved in cognition have not been fully elucidated. Brain-derived neurotrophic factor (BDNF) has a role in neuronal plasticity and cognition. However, the relationship between cognitive performance and serum BDNF levels has not been demonstrated in an African population. This study aimed to assess cognition and BDNF level and determine their relationship in a population of healthy adult Africans. Materials and Methods: Cognitive function and BDNF were determined using Mini Mental State Examination and enzyme-linked immunosorbent assay kit, respectively. SPSS statistics was used to process data. Results: Thirty male and female volunteers with a mean age of 48.7 ± 11.32 years were studied. The median cognitive score was 24.00 (21 and 28) with no sex variation (U = 107, P = 0.833). The median value of serum BDNF concentration was 2.09 ± 0.15 ng/L and statistically the same in males and females (t = 1.276, P = 0.213). Cognitive score correlated moderately with BDNF level (r = 0.369, P = 0.045), but not with sociodemographic or anthropometric characteristics. Conclusion and Recommendation: It was concluded that the population studied had normal cognitive function, which was not affected by sociodemographic and anthropometric characteristics. BDNF was a mediator of global cognitive function and was positively associated with registration and negatively associated with language domains of cognition. Peripheral levels of BDNF may potentially serve as a biomarker and index of cognitive evaluation in clinical settings.

Effect of Exercise on Major Depressive Disorder and Schizophrenia: A BDNF Focused Approach.

Psychiatric disorders are remarkable health problems that cause a massive social and economic burden, and the issue of their long-term and effective treatment is subjected to discussion. The effect of physical activity and exercise is under investigation in the treatment of the major depressive disorder (MDD) and schizophrenia which are accompanied by cognitive dysfunctions. Scientists focus on the positive effects of exercise on learning, memory and attention parameters while investigating the regulatory role of brain-derived neurotrophic factor (BDNF). In this review, the effect of aerobic exercise on peripheral BDNF levels in MDD and schizophrenia is examined by including human studies in which acute and chronic aerobic exercise are applied. The results showed that aerobic exercise caused different responses on BDNF levels, and some of the studies were accompanied by the improvement in cognitive functions in BDNF changes. In order to comprehend the effect of aerobic exercise in MDD and schizophrenia, it is understood that applying studies on larger and paired participant groups with different exercise frequencies and tensions in necessary.

Brain-derived neurotrophic factor: Biopsychosocial correlates and exercise response in mild traumatic brain injury

Recovery from mild traumatic brain injury (mTBI) is a dynamic, complex process, and pre-clinical research highlights brain-derived neurotrophic factor (BDNF) as an important mediator in functional and pathophysiologic outcomes. Although BDNF appears to also be a significant factor in recovery in humans, its role is less understood. Our purpose was (1) to examine the association of serum and platelet-poor plasma concentrations of BDNF to relevant biopsychosocial outcomes of mTBI recovery (i.e., neurocognitive performance [attention, processing speed, memory, executive functioning], sleep, balance, mood, and self-reported symptoms) and (2) to assess BDNF response to a single-session of aerobic exercise (40 minutes of stationary cycling at 65%–75% maximum heart rate). There were 36 participants (ages 18–40; 19 male, 17 female) in 2 groups: (1) mTBI participants (n = 26) who were 14–25 days post-injury were randomized to either aerobic or non-aerobic exercise (low intensity stretching) and (2) demographically-matched, non-injured participants (n = 10) who participated in a single session of aerobic exercise. Results indicate that serum BDNF concentration has significant ( p = 0.05), inverse relationships with both sleep dysfunction and state levels of anxiety. No significant association between exercise type and serum BDNF was found, but there was a small to medium effect size (= 0.08) for increased plasma BDNF after aerobic exercise in mTBI vs non-injured participants. Overall, peripheral BDNF concentrations are poorly correlated, which suggests they reflect different tissue sources. Serum BDNF was more sensitive to select biopsychosocial outcomes, particularly sleep quality and anxiety, regardless of injury status. Additionally, aerobic exercise may play a role in enhancing platelet-poor plasma BDNF response in the post-acute period after mTBI.

Memory Impairment and Plasma BDNF Correlates of the BDNF Val66Met Polymorphism in Patients With Bipolar II Disorder

Studies suggest that a functional polymorphism of brain-derived neurotrophic factor (BDNF), polymorphism BDNF Val66Met affects cognitive functions, however, the effect is unclear in bipolar II (BD-II) disorder. We used the Wechsler Memory Scale-third edition (WMS-III), the presence of the BDNF Val66Met polymorphism, and plasma concentrations of BDNF to investigate the association between memory impairment and BDNF in BD-II disorder. We assessed the memory functions of 228 BD-II patients and 135 healthy controls (HCs). BD-II patients had significantly lower scores on five of the eight WMS-III subscales. In addition to education, the BDNF polymorphism were associated with the following subscales of WMS-III, auditory delayed memory, auditory delayed recognition memory and general memory scores in BD-II patients, but not in HC. Moreover, BD-II patients with the Val-homozygote scored significantly higher on the visual immediate memory subscale than did those with the Met/Met and Val/Met polymorphisms. The significantly positive effect of the Val-homozygote did not have a significantly positive effect on memory in the HC group, however. We found no significant association between BDNF polymorphisms and plasma concentrations of BDNF. The plasma BDNF was more likely to be associated with clinical characteristics than it was with memory indices in the BD-II group. The impaired memory function in BD-II patients might be dependent upon the association between the BDNF Val66Met polymorphism and peripheral BDNF levels.

Objective sleep duration is associated with cognitive deficits in primary insomnia: BDNF may play a role.

Objective sleep duration has been linked to insomnia severity. However, cognitive functions of people with insomnia with different sleep durations have been seldom addressed. Brain-derived neurotrophic factor (BDNF) has an important role in cognitive function and has been linked to clinical insomnia recently. The present study aimed to evaluate the comprehensive cognitive functions in people with primary insomnia with different objective sleep durations, and further examine the involvement of peripheral BDNF. Fifty-seven people with insomnia were subdivided into short sleep duration (SSD, sleep time < 6 hr) group and normal sleep duration (NSD, sleep time ≥ 6 hr) group based on polysomnography data. Twenty-nine healthy controls (HC) were matched on age, gender, and education. Cognitive function was assessed using a comprehensive and sensitive neuropsychological test battery. Both objective and subjective insomnia statuses were estimated. Serum BDNF level was measured using enzyme-linked immune sorbent assay. Compared with HC, the SSD group showed impaired neuropsychological performances in spatial span, brief visuospatial memory test, fluency, managing emotions, and continuous performance tests. In contrast, NSD had bad performance only in brief visuospatial memory test and continuous performance tests, and relatively better than SSD group in the latter test. People with SSD insomnia but not NSD had decreased BDNF levels compared with HC, and neuropsychological performance was positively correlated with BDNF levels only in SSD group. Primary insomnia was associated with impaired neuropsychological performance, and the impairment might be related to decreased objective sleep duration. In addition, decreased peripheral BDNF might mediate the impaired cognitive functions of people with insomnia with SSD.

Serum Tryptophan, Tryptophan Catabolites and Brain-derived Neurotrophic Factor in Subgroups of Youngsters with Autism Spectrum Disorders.

There is evidence that changes in neuro-immune responses coupled with dysfunctions in serotonin metabolism underpin the pathophysiology of autism spectrum disorders (ASD). This study aimed to delineate whether ASD subgroups or characteristics show aberrations in tryptophan and brain-derived neurotrophic factor (BDNF) metabolism. 65 individuals with ASD (diagnosed according to ICD criteria) and 30 healthy control patients were included. Measured were serum levels of tryptophan, kynurenine (KYN), kynurenic acid (KA), quinolinic acid (QA), BDNF and PRO-BDNF and total blood 5-HT and 5-OH-tryptophan (5-HTP). Elevated BDNF levels and lower tryptophan and KA levels were characteristics of both childhood autism and intellectual disability disorder, whilst elevated tryptophan and lower 5-HT synthesis were hallmarks of Asperger syndrome. A pathological MRI was associated with elevated tryptophan and lowered KA. Abnormal EEG results and dysmorphology were both associated with an elevated BDNF/ PRO-BDNF ratio. Any brain pathology and gastro-intestinal symptoms were accompanied by lowered KA. Increased BDNF production and changes in the metabolism of tryptophan are associated with many ASD characteristics, showing particularly strong associations with childhood autism and Intellectual and Developmental Disabilities. Peripheral BDNF and tryptophan metabolism appear to take part in the pathophysiology of autism spectrum disorders and their phenotypes.