Serum Brain-derived Neurotrophic Factor Concentrations Research Articles

Serum concentration and clinical significance of brain-derived neurotrophic factor in patients with Parkinson’s disease or essential tremor

ObjectivesThe serum concentration of brain-derived neurotrophic factor (BDNF) was compared among patients with Parkinson’s disease (PD), patients with essential tremor (ET), and healthy participants, and its association with clinical features of PD and ET was assessed.MethodsDemographic and clinical data were collected from 60 patients with PD at different clinical stages, 60 patients with ET, and 60 controls. All participants’ serum BDNF concentrations were measured. Their motor abilities and activity were assessed by the Unified PD Rating Scale and the Hoehn and Yahr (H-Y) staging scale.ResultsSerum BDNF was significantly lower in patients with PD than in patients with ET and controls. BDNF decreased only in the early disease stages (H-Y stages I and II), but increased markedly in the advanced stages (H-Y stages III–V). There was no significant difference between patients with ET and controls. The BDNF concentration was negatively correlated with age at PD onset and positively associated with disease duration, severity of PD symptoms, and treatment with L-DOPA.ConclusionsA low serum BDNF concentration may serve as a biomarker in the early stages of PD, whereas a high concentration with PD progression may be due to treatment with L-DOPA in the advanced stages.

Effect of combined exercise training on serum brain-derived neurotrophic factor, suppressors of cytokine signaling 1 and 3 in patients with multiple sclerosis

BackgroundSuppressors of cytokine signaling (SOCS) and brain-derived neurotrophic factor (BDNF) are important immunologic, and neurotrophic factors for MS pathogenesis. The impact of exercise on these factors is yet to be fully elucidated in patients with MS. ObjectiveThe primary aim of this study is to investigate the effect of 8-week combined exercise training on serum concentrations of SOCS1, SOCS3, and BDNF. The secondary aim is to determine the effects of combined exercise training on balance, functional exercise capacity, and fatigue in patients with MS. MethodsSerum SOCS1, SOCS3, and BDNF levels were assessed in 36 MS patients and 18 healthy individuals. In addition, balance, functional exercise capacity, and fatigue were assessed in the patients with MS. The patients were randomly divided into the combined exercise group (MS-EX, n:18) and the control group (MS-C, n:18). MS-EX received an 8-week combined exercise training. ResultsThe serum SOCS1, SOCS3, and BDNF levels were similar in the MS patients and healthy control (HC). In MS-EX, the serum BDNF level, balance, functional exercise capacity, and fatigue improved after 8weeks (p<0.05), but the serum SOCS1, and SOCS3 levels did not change significantly (p>0.05). In MS-C, the serum SOCS1 level, and fatigue increased significantly after 8weeks (p<0.05), but serum SOCS3, BDNF, balance and functional exercise capacity did not change (p>0.05). ConclusionsIn summary, the combined exercise training improved BDNF, and physical performance in patients with MS. But, future studies are needed to clarify the role of SOCS proteins in MS pathogenesis and the effect of exercise on SOCS.

SERUM BRAIN DERIVED NEUROTROPHIC FACTOR AS BIOMARKER FOR EPILEPSY DIAGNOSIS IN EGYPTIAN CHILDREN WITH EPILEPSY; RELATIONSHIP TO DISEASE SEVERITY AND COGNITIVE FUNCTION.

Objectives: This study was designed to estimate serum brain-derived neurotrophic factor (BDNF) concentration in a group of Egyptian children with epilepsy to clarify its utility as a biomarker for epilepsy diagnosis and to evaluate its relationship with their cognitive function and disease severity. Methods: Intelligence was assessed using Arabic version of the WISC-R test. Serum concentration of BDNF was assessed using enzyme-linked immunosorbent assay in 40 children with epilepsy and 40 apparently healthy children of matched age and sex controls. Results: Of total 40 epileptic patients aged 6–12 years, the mean age was 8.32 ± 0.7 years and male to female ratio was 1.5:1. The mean serum BDNF concentration and cognitive IQ scores were statistically significantly reduced in the studied patient’s group versus to controls (p&lt;0.001). There were highly significant differences in serum BDNF concentration as regards epileptic severity. Serum concentration of BDNF showed significantly positive correlation with cognitive, verbal, performance, and totals IQ scores and negative correlation with the age at the onset of seizures, and duration of therapy. The linear regression analysis showed a statistically significant association between age at the onset of seizures, duration of therapy, cognitive function, and serum BDNF concentrations among the studied patients. Conclusions: Concentration of BDNF in serum is involved in the mechanism of epileptogenesis in children with epilepsy. It should be used as a helpful marker for epilepsy diagnosis and detection of severity.

SERUM BRAIN DERIVED NEUROTROPHIC FACTOR AS BIOMARKER FOR EPILEPSY DIAGNOSIS IN EGYPTIAN CHILDREN WITH EPILEPSY; RELATIONSHIP TO DISEASE SEVERITY AND COGNITIVE FUNCTION.

Objectives: This study was designed to estimate serum brain-derived neurotrophic factor (BDNF) concentration in a group of Egyptian children with epilepsy to clarify its utility as a biomarker for epilepsy diagnosis and to evaluate its relationship with their cognitive function and disease severity. Methods: Intelligence was assessed using Arabic version of the WISC-R test. Serum concentration of BDNF was assessed using enzyme-linked immunosorbent assay in 40 children with epilepsy and 40 apparently healthy children of matched age and sex controls. Results: Of total 40 epileptic patients aged 6–12 years, the mean age was 8.32 ± 0.7 years and male to female ratio was 1.5:1. The mean serum BDNF concentration and cognitive IQ scores were statistically significantly reduced in the studied patient’s group versus to controls (p&lt;0.001). There were highly significant differences in serum BDNF concentration as regards epileptic severity. Serum concentration of BDNF showed significantly positive correlation with cognitive, verbal, performance, and totals IQ scores and negative correlation with the age at the onset of seizures, and duration of therapy. The linear regression analysis showed a statistically significant association between age at the onset of seizures, duration of therapy, cognitive function, and serum BDNF concentrations among the studied patients. Conclusions: Concentration of BDNF in serum is involved in the mechanism of epileptogenesis in children with epilepsy. It should be used as a helpful marker for epilepsy diagnosis and detection of severity.

C-reactive protein, brain-derived neurotrophic factor, interleukin-2, and stressful life events in drug-naive first-episode and recurrent depression: A cross-sectional study.

Aims:The aim of the study is to assess and compare serum C-reactive protein (CRP), brain derived neurotrophic factor (BDNF), and interleukin-2 (IL-2) levels in patients with first-episode depression (FED), recurrent depressive disorder (RDD), and healthy controls (HCs) and to determine the relationship between the above-specified inflammatory markers, severity of depression, and stressful life events.Materials and Methods:Consecutive drug-naive patients with FED and RDD (n = 85) and 50 HCs were studied. Serum concentrations of CRP, brain-derived nerve growth factor (BDNF), and IL-2 were measured. All participants were assessed using Mini-International Neuropsychiatric Interview Plus, Beck's depression inventory, and presumptive stressful life events scale.Results:The FED and RDD groups had statistically significant lower serum concentration of BDNF and higher IL-2 compared to the HC group, whereas no statistically significant difference was observed with regard to CRP level. No statistically significant differences were observed with regard to the severity of depression and serum concentrations of CRP, BDNF, and IL-2 in the FED and RDD groups. No significant correlation was found between severity of depression and serum concentration of CRP, BDNF, and IL-2 in both the groups. Serum CRP concentration was significantly higher in patients with ≥2 stressful life events. No significant difference was observed between number of stressful life events and BDNF and IL-2 in patients with depression.Conclusion:FED and RDD are associated with lower serum concentration of BDNF and higher IL-2 compared to the HCs, whereas there appears no difference with regard to CRP level. Multicentric studies are needed to further elucidate the role of inflammatory markers in depression.

ANXIOUS-DEPRESSIVE SYMPTOMATOLOGY AND BRAIN-DERIVED NEUROTROPHIC FACTOR LEVEL IN PATIENTS WITH TENSION HEADACHE

Aim. To study the correlation between the blood serum brain-derived neurotrophic factor (BDNF) level and the manifestation of anxious-depressive symptomatology in patients with tension headache. Materials and methods. The study involved 82 patients with tension headache. The method of immune-enzyme assay with test-system ELISA kit was used to measure the blood serum BDNF concentration. Results. The BDNF level in patients with episodic infrequent and frequent tension headaches was comparable with the group of control. Among patients with chronic tension headache, decrease in BDNF level as compared to group 1, group 2 and the control was revealed. The BDNF level is changed, depending on the duration and intensiveness of tension headache. Conclusions. Chronic tension headache causes exhaustion of not only mediator, but of neurotrophic systems of the brain as well. Blood serum BDNF concentration measured permits to assess activity of cerebral neuroplastic processes and to choose neurotrophic therapy for a more rapid triggering of serotoninergic system and arresting of anxious-depressive syndrome.

Effect of maternal iron deficiency anemia on fetal neural development.

Perinatal iron deficiency may have deleterious consequences on fetal neural development. The present study was conducted to determine the effect of maternal iron deficiency anemia (IDA) on fetal hippocampal morphogenesis and production of brain-derived neurotrophic factor (BDNF). Seventy term, singleton neonates born to mothers with IDA (hemoglobin <110g/L and serum ferritin <12 μg/L) formed the study group. Twenty gestational age-matched neonates born to healthy mothers without IDA (hemoglobin ≥110 g/L and serum ferritin >12 μg/L) served as controls. Maternal and fetal inflammatory conditions, infections and neonates with perinatal asphyxia were excluded. Cord blood BDNF concentrations were estimated by enzyme-linked immunosorbent assay. Volumetric analysis of hippocampus (right, left and combined, corrected for total intracranial volume) was done by cranial magnetic resonance imaging on days 3-5 of life. In the study group, 24 mothers had mild (hemoglobin 100.0-109.0 g/L), 24 had moderate (hemoglobin 70.0-99.0 g/L), and 22 had severe (hemoglobin <70.0 g/L) anemia. Both hippocampal volumes and serum BDNF concentrations of neonates born to iron-deficient mothers were significantly reduced compared to controls. A progressive decline in hippocampal volumes and BDNF concentrations was observed with increasing severity of maternal anemia. Pearson correlation showed significant correlations among maternal and cord blood hemoglobin, iron indices, hippocampal volumes and BDNF concentrations. Maternal IDA adversely affects hippocampal morphogenesis and fetal production of BDNF. The degree of affection is proportional to the severity of maternal anemia.

Relationships between serum brain-derived neurotrophic factor concentration and parameters for health scores in community-dwelling older adults.

Brain-derived neurotrophic factor (BDNF) have been implicated in the progression of neuronal survival, phenotyping differentiation and maintenance of various neurons, as well as neurogenesis. We studied how BDNF affects health parameters of older adults by carrying out a health examination of community-dwelling older adults. We measured the serum BDNF concentration of 898 older adults aged 65-84 years who participated in regional health examinations in the Tokyo area and also measured various parameters, such as the thickness of the quadriceps femoris, percentage of body fat, body mass index, grip strength, frequency of walking, and use of sleeping drugs and steroidal anti-inflammatory drugs. We obtained significant relationships between serum BDNF values and thickness of the quadriceps muscle, body mass index or percentage of body fat. Individuals holding onto something when they stood up had lower serum BDNF values than individuals not holding onto something when they stood up. Smokers had higher serum BDNF values than non-smokers. Older adults who had higher serum BDNF had bigger quadriceps muscles, higher body mass index and higher body fat rate, and were also able to stand up without holding onto something from a sitting position. Geriatr Gerontol Int 2018; 18: 456-461.

The Alteration of Irisin-Brain-Derived Neurotrophic Factor Axis Parallels Severity of Distress Disorder in Bronchial Asthma Patients.

Distress disorder (a collective term for generalized anxiety disorder and major depressive disorder) is a well-known co-morbidity of bronchial asthma. The irisin—brain-derived neurotrophic factor (BDNF) axis is a pathway that influences several neurobehavioral mechanisms involved in the pathogenesis of distress disorder. Thus, the aim of the present study was to quantify the serum irisin and BDNF concentrations in order to investigate the possible link between the irisin/BDNF axis and distress disorder in an asthma patient cohort. Data of 167 therapy-controlled asthma patients were analyzed. Demographic, anthropometric, and anamnestic data were collected, routine laboratory parameters supplemented with serum irisin and BDNF levels were determined, pulmonary function test was performed using whole-body plethysmography, and quality of life was quantified by means of the St. George's Respiratory Questionnaire (SGRQ). Correlation analysis as well as simple and multiple linear regression were used to assess the relationship between the irisin level and the Impacts score of SGRQ, which latter is indicative of the presence and severity of distress disorder. We have found a significant, positive linear relationship between the Impacts score and the reciprocal of irisin level. This association was stronger in patients whose BDNF level was higher, and it was weaker (and statistically non-significant) in patients whose BDNF level was lower. Our results indicate that higher serum irisin level together with higher serum BDNF level are associated with milder (or no) distress disorder. This finding suggests that alteration of the irisin/BDNF axis influences the presence and severity of distress disorder in asthma patients.

The association between brain-derived neurotrophic factor and central pulse pressure after an oral glucose tolerance test

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

Decreased Serum Brain-Derived Neurotrophic Factor May Indicate the Development of Poststroke Depression in Patients with Acute Ischemic Stroke: A Meta-Analysis

Depression is a common complication after stroke and has been associated with poor outcome. Thus, it is of great importance to identify potential biomarkers that can aid in predicting and detecting patients with stroke at high risk of poststroke depression (PSD) development. Previous studies showed that brain-derived neurotrophic factor (BDNF) had potential use as a biomarker for discriminating patients with stroke at high risk of PSD. However, the results were inconsistent. A meta-analysis was performed to evaluate the correlation between the peripheral BDNF levels and the development of PSD in the acute stage of stroke. Data were obtained from 4 studies including 499 patients with stroke. Among them, 171 patients were diagnosed with PSD at follow-ups. Our results showed that patients with stroke who were predisposed to developing PSD had significantly lower serum BDNF concentrations at the early stage of stroke. This study suggests a potential association between circulating BDNF concentrations at admission and subsequent PSD development, and provides additional support for the involvement of BDNF in the PSD development.

Val66Met functional polymorphism and serum protein level of brain-derived neurotrophic factor (BDNF) in acute episode of schizophrenia and depression.

Brain-derived neurotrophic factor (BDNF) influences neuron differentiation during development as well as the synaptic plasticity and neuron survival in adulthood. BDNF has been implicated in the pathogenesis of schizophrenia and depression. Val66Met polymorphism and BDNF serum level are potential biomarkers in neuropsychiatric disorders. The aim of this study was to determine the effect of BDNF gene Val66Met functional polymorphism on serum BDNF concentration in patients with schizophrenia, during depression episode and in healthy control group. 183 participants were recruited (61 patients with depressive episode, 56 females with schizophrenia, 66 healthy controls) from Polish population. Serum BDNF levels were measured using ELISA method. Val66Met polymorphism was genotyped using PCR- RFLP method. Serum BDNF levels were not associated with Val66Met polymorphism in either of the groups. A significant increase of BDNF level in schizophrenia (p = 0.0005) and depression (p = 0.026) comparing to the control group has been observed. Our results suggest that the functional Val66Met BDNF polymorphism is not associated with BDNF serum levels, which is in line with previous findings. Replication studies on larger groups are needed.

Novel Blood-Based Biomarkers of Cognition, Stress, and Physical or Cognitive Training in Older Adults at Risk of Dementia: Preliminary Evidence for a Role of BDNF, Irisin, and the Kynurenine Pathway.

Psychosocial stress and physical, cognitive, and social activity predict the risk of cognitive decline and dementia. The aim of this study was to elucidate brain-derived neurotrophic factor (BDNF), irisin, and the kynurenine pathway (KP) as potential underlying biological correlates. We evaluated associations of irisin and the KP with BDNF in serum and with cognition, stress, and activities. Furthermore, changes in serum concentrations of BDNF, irisin, and KP metabolites were investigated after physical or cognitive training. Forty-seven older adults at risk of dementia were assigned to 10 weeks of physical training, cognitive training, or await-list control condition. Previous physical, cognitive, and social activities and stressful life events were recorded; global cognition, episodic memory, and executive functions were assessed. Serum levels of L-kynurenine, kynurenic acid, 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN) were determined by validated assays based on liquid chromatography coupled to tandem mass spectrometry. BDNF and irisin serum levels were determined with enzyme-linked immunosorbent assays. BDNF and irisin correlated positively with global cognition and episodic memory, while the neurotoxic metabolite QUIN correlated negatively with executive functions. Stressful life events were associated with reduced BDNF and increased 3-HK. 3-HK decreased after cognitive training, while BDNF tended to increase after physical training. This suggests that psychosocial stress as well as cognitive and physical training may impact BDNF serum levels and the KP. Irisin and QUIN may constitute novel serum biomarkers of cognitive impairment, in addition to BDNF. Larger scale trials are needed to replicate and extend these novel findings.

Correlates of early pregnancy serum brain-derived neurotrophic factor in a Peruvian population.

Knowledge about factors that influence serum brain-derived neurotrophic factor (BDNF) concentrations during early pregnancy is lacking. The aim of the study is to examine the correlates of early pregnancy serum BDNF concentrations. A total of 982 women attending prenatal care clinics in Lima, Peru, were recruited in early pregnancy. Pearson's correlation coefficient was calculated to evaluate the relation between BDNF concentrations and continuous covariates. Analysis of variance and generalized linear models were used to compare the unadjusted and adjusted BDNF concentrations according to categorical variables. Multivariable linear regression models were applied to determine the factors that influence early pregnancy serum BDNF concentrations. In bivariate analysis, early pregnancy serum BDNF concentrations were positively associated with maternal age (r=0.16, P<0.001) and early pregnancy body mass index (BMI) (r=0.17, P<0.001), but inversely correlated with gestational age at sample collection (r=-0.21, P<0.001) and C-reactive protein (CRP) concentrations (r=-0.07, P<0.05). In the multivariable linear regression model, maternal age (β=0.11, P=0.001), early pregnancy BMI (β=1.58, P<0.001), gestational age at blood collection (β=-0.33, P<0.001), and serum CRP concentrations (β=-0.57, P=0.002) were significantly associated with early pregnancy serum BDNF concentrations. Participants with moderate antepartum depressive symptoms (Patient Health Questionnaire-9 (PHQ-9) score≥10) had lower serum BDNF concentrations compared with participants with no/mild antepartum depressive symptoms (PHQ-9 score<10). Maternal age, early pregnancy BMI, gestational age, and the presence of moderate antepartum depressive symptoms were statistically significantly associated with early pregnancy serum BDNF concentrations in low-income Peruvian women. Biological changes of CRP during pregnancy may affect serum BDNF concentrations.

Stability of BDNF in Human Samples Stored Up to 6 Months and Correlations of Serum and EDTA-Plasma Concentrations.

Brain-derived neurotrophic factor (BDNF), an important neural growth factor, has gained growing interest in neuroscience, but many influencing physiological and analytical aspects still remain unclear. In this study we assessed the impact of storage time at room temperature, repeated freeze/thaw cycles, and storage at −80 °C up to 6 months on serum and ethylenediaminetetraacetic acid (EDTA)-plasma BDNF. Furthermore, we assessed correlations of serum and plasma BDNF concentrations in two independent sets of samples. Coefficients of variations (CVs) for serum BDNF concentrations were significantly lower than CVs of plasma concentrations (n = 245, p = 0.006). Mean serum and plasma concentrations at all analyzed time points remained within the acceptable change limit of the inter-assay precision as declared by the manufacturer. Serum and plasma BDNF concentrations correlated positively in both sets of samples and at all analyzed time points of the stability assessment (r = 0.455 to rs = 0.596; p < 0.004). In summary, when considering the acceptable change limit, BDNF was stable in serum and in EDTA-plasma up to 6 months. Due to a higher reliability, we suggest favoring serum over EDTA-plasma for future experiments assessing peripheral BDNF concentrations.

Brain derived neurotrophic factor profile in children with ischemic stroke

Objective: Assessment of brain derived neurotrophic factor (BDNF) serum levels in children who have suffered an ischemic stroke (1 month after stroke) and establishment of the correlation between BDNF serum levels and imaging and neurophysiological changes. Methods: The study included a sample of 26 children, aged between 1 and 3 months, with ischemic stroke because of perinatal hypoxic-ischemic lesions of the central nervous system (CNS); 25 children, in the same age group, were included in the control group. Enzyme-linked Immunosorbent Assay (ELISA) was used to test the serum BDNF levels. Neurophysiological and neuroimaging exams were performed. Statistical analyses were obtained by the correlation coefficient (Pearson) and ANOVA test. Results: Preliminary study results showed that compared to control group, the children who have suffered ischemic stroke, showed significantly lower serum BDNF levels (p<0.01). In the study group, low BDNF levels correlated with the degree of neuroimaging modifications (rxy=−0.72, p<0.05) and neurophysiological changes (rxy=−0.74, p<0.05). During 3 years after stroke, children with low levels of BDNF developed cerebral palsy and epilepsy. Conclusion: Children that suffered an ischemic stroke because of perinatal hypoxic-ischemic lesions of the CNS had a significantly lower serum BDNF concentrations compared to the control group. Low BDNF levels correlate with the severity of neurophysiological and neuroimaging changes and play an important role in the development of cerebral palsy and epilepsy.

Differences In Plasma And Serum BDNF In Response To Acute HIIE

PURPOSE: Circulating concentrations of brain-derived neurotrophic factor (BDNF) are reported to increase with acute exercise in a dose-dependent manner; however, the sources of elevated plasma and serum BDNF may differ as workload increases. Elevated plasma BDNF concentrations are believed to reflect release by the brain, which can indicate positive adaptations in brain health, whereas elevations in serum may reflect increased platelet release by the spleen. The popularity and documented benefits of high intensity interval exercise (HIIE), prompted the aim of this study to clarify the acute effects of low-volume, supramaximal HIIE on circulating BDNF. Furthermore, to examine a possible explanation for the changes in plasma BDNF, irisin, a protein involved in the mechanism linking muscle contraction and hippocampal BDNF release, was measured in plasma. METHODS: Healthy, sedentary males (N=11) participated in HIIE on a cycle ergometer (10 x 20 seconds of maximal pedaling against 5.5% of the subject’s body weight x 10 seconds of rest). Whole blood samples were collected from the antecubital vein prior to, immediately after (POST), and 15 minutes after (15POST) HIIE for BNDF and irisin analyses. RESULTS: At rest, serum BDNF concentrations were nearly 40-fold greater compared to plasma. Although no changes in plasma BDNF were observed after HIIE, serum BDNF increased at POST and 15POST (F (2,40) = 7.277, p = 0.002). Plasma irisin concentrations significantly decreased at POST (p = 0.029). In addition, a positive association between the total change in irisin and total change in plasma BDNF approached significance (r = 0.501, p = 0.097). CONCLUSIONS: These findings demonstrated that this low-volume, supramaximal HIIE protocol was sufficient for elevating serum BDNF, but not adequate for increasing circulating plasma BDNF in sedentary males. These results may suggest that the intensity of physical activity can differentially affect plasma and serum levels of BDNF. Additional research on HIIE volume and the mechanisms underlying BDNF responses (e.g. irisin) is warranted.

The link between sleep, stress and BDNF

The protein brain derived neurotrophic factor (BDNF) is a major contributor to neuronal plasticity. There is numerous evidence that BDNF expression is decreased by experiencing psychological stress and that accordingly a lack of neurotrophic support causes depression. The use of serum BDNF concentration as a potential indicator of brain alteration is justified through extensive evidence. Recently, we reported, for the first time, a relationship between BDNF and insomnia, since we could show that reduced levels of serum BDNF are correlated with sleep impairment in control subjects, while partial sleep deprivation was able to induce a fast increase in serum BDNF levels in depressed patients. Using a bi-directional stress model as an explanation approach, we propose the hypothesis that chronic stress might induce a deregulation of the HPA system leading in the long term to sleep disturbance and decreased BDNF levels, whereas acute sleep deprivation, can be used as therapeutical intervention in some insomniac or depressed patients as compensatory process to normalize BDNF levels. Indeed, partial sleep deprivation (PSD) induced a very fast increase in BDNF serum levels within hours after PSD which is similar to effects seen after ketamine infusion, another fast-acting antidepressant intervention, while traditional antidepressants are characterized by a major delay until treatment response as well as delayed BDNF level increase. Moreover, we revealed that stress experience and subjective sleep perception interact with each other and affect serum BDNF levels. We identified sleep as a mediator of the association between stress experience and serum BDNF levels.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Affective alterations in patients with Cushing's syndrome in remission are associated with decreased BDNF and cortisone levels.

Affective alterations and poorer quality of life often persist in patients with Cushing's syndrome (CS) in remission. Brain-derived neurotrophic factor (BDNF) regulates the hypothalamic-pituitary-adrenal axis (HPA) and is highly expressed in brain areas controlling mood and response to stress. Our aims were to assess affective alterations after long-term remission of CS and evaluate whether they are associated with serum BDNF, salivary cortisol (SalF) and/or cortisone (SalE) concentrations. Thirty-six CS patients in remission (32 females/4 males; mean age (±s.d.), 48.8 ± 11.8 years; median duration of remission, 72 months) and 36 gender-, age- and BMI-matched controls were included. Beck Depression Inventory-II (BDI-II), Center for Epidemiological Studies Depression Scale (CES-D), Positive Affect Negative Affect Scale (PANAS), State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS) and EuroQoL and CushingQoL questionnaires were completed and measured to evaluate anxiety, depression, stress perception and quality of life (QoL) respectively. Salivary cortisol was measured using liquid chromatography/tandem mass spectrometry (LC/TMS). BDNF was measured in serum using an ELISA. Remitted CS patients showed worse scores in all questionnaires than controls: STAI (P < 0.001), BDI (P < 0.001), CES-D (P < 0.001), PANAS (P < 0.01), PSS (P < 0.01) and EuroQoL (P < 0.01). A decrease in BDNF was observed in CS vs controls (P = 0.038), and low BDNF was associated with more anxiety (r = -0.247, P = 0.037), depression (r = -0.249, P = 0.035), stress (r = -0.277, P = 0.019) and affective balance (r = 0.243, P = 0.04). Morning salivary cortisone was inversely associated with trait anxiety (r = -0.377, P = 0.040) and depressed affect (r = -0.392, P = 0.032) in CS patients. Delay to diagnosis was associated with depressive symptoms (BDI-II: r = 0.398, P = 0.036 and CES-D: r = 0.449, P = 0.017) and CushingQoL scoring (r = -0.460, P < 0.01). Low BDNF levels are associated with affective alterations in 'cured' CS patients, including depression, anxiety and impaired stress perception. Elevated levels of SalE might also be related to poor affective status in these patients.

High-Intensity Locomotor Exercise Increases Brain-Derived Neurotrophic Factor in Individuals with Incomplete Spinal Cord Injury.

High-intensity locomotor exercise is suggested to contribute to improved recovery of locomotor function after neurological injury. This may be secondary to exercise-intensity-dependent increases in neurotrophin expression demonstrated previously in control subjects. However, rigorous examination of intensity-dependent changes in neurotrophin levels is lacking in individuals with motor incomplete spinal cord injury (SCI). Therefore, the primary aim of this study was to evaluate the effect of locomotor exercise intensity on peripheral levels of brain-derived neurotrophic factor (BDNF) in individuals with incomplete SCI. We also explored the impact of the Val66Met single-nucleotide polymorphism (SNP) on the BDNF gene on intensity-dependent changes. Serum concentrations of BDNF and insulin-like growth factor-1 (IGF-1), as well as measures of cardiorespiratory dynamics, were evaluated across different levels of exercise intensity achieved during a graded-intensity, locomotor exercise paradigm in 11 individuals with incomplete SCI. Our results demonstrate a significant increase in serum BDNF at high, as compared to moderate, exercise intensities (p = 0.01) and 15 and 30 min post-exercise (p < 0.01 for both), with comparison to changes at low intensity approaching significance (p = 0.05). Serum IGF-1 demonstrated no intensity-dependent changes. Significant correlations were observed between changes in BDNF and specific indicators of exercise intensity (e.g., rating of perceived exertion; R = 0.43; p = 0.02). Additionally, the data suggest that Val66Met SNP carriers may not exhibit intensity-dependent changes in serum BDNF concentration. Given the known role of BDNF in experience-dependent neuroplasticity, these preliminary results suggest that exercise intensity modulates serum BDNF concentrations and may be an important parameter of physical rehabilitation interventions after neurological injury.