Brain-derived Neurotrophic Factor In Patients Research Articles

Brain-derived neurotrophic factor in patients with normal-tension glaucoma

Purpose The aim of this study was to detect and measure brain-derived neurotrophic factor (BDNF) in the tears of normal subjects and patients with normal-tension glaucoma (NTG). Materials and Methods Twenty patients with NTG as the case group and 20 normal subjects with the same age range as the control group were tested. The control group consisted of 16 men and 4 women, ranging in age from 40 to 75, without any apparent ocular or systemic disease. The case group consisted of 15 men and 5 women, ranging in age from 45 to 74. BDNF levels in tears were determined by enzyme-linked immunosorbent assay using monoclonal antibodies specific for BDNF (R&D Systems, Minneapolis, Minnesota). Results The mean level of BDNF detected in the tears of the normal subjects was 77.09 ± 4.84 ng/mL and the BDNF levels in the tears of case group were 24.33 ± 1.48 ng/mL (P < 0.001). Conclusion We suggest that BDNF in the tears might be a useful biochemical marker for early detection of normal-tension glaucoma (NTG).

Acute exercise ameliorates reduced brain-derived neurotrophic factor in patients with panic disorder

The neurotrophin brain-derived neurotrophic factor (BDNF) has been implicated in depression and anxiety. Antidepressants and exercise increase BDNF expression, and both have an antidepressant and anxiolytic activity. To further characterize the association of anxiety, BDNF and exercise, we studied panic disorder patients (n=12) and individually matched healthy control subjects (n=12) in a standardized exercise paradigm. Serum samples for BDNF analyses were taken before and after 30min of exercise (70 VO(2max)) or quiet rest. The two conditions were separated by 1 week and the order was randomized. Non-parametric statistical analyses were performed. There was a negative correlation of BDNF concentrations and subjective arousal at baseline (r=-0.42, p=0.006). Compared to healthy control subjects, patients with panic disorder had significantly reduced BDNF concentrations at baseline and 30min of exercise significantly increased BDNF concentrations only in these patients. Our results suggest that acute exercise ameliorates reduced BDNF concentrations in panic disorder patients and raise the question whether this is also found after long-term exercise training and if it is related to the therapeutic outcome.

Increased levels of plasma brain-derived neurotrophic factor (BDNF) in children with attention deficit-hyperactivity disorder (ADHD)

Background Recent reports have suggested a pathophysiological role of brain-derived neurotrophic factor (BDNF) in attention deficit-hyperactivity disorder (ADHD). We evaluated the plasma levels of BDNF in patients with ADHD. Methods Plasma BDNF levels were measured in 41 drug naive ADHD patients and 107 normal controls. The severity of ADHD symptoms was determined by patient scores on the ADHD rating scale (ARS) and the computerized ADHD diagnostic system (ADS). Results ANCOVA with age and gender as covariates showed that the mean plasma BDNF levels were significantly higher in ADHD patients than in normal controls ( F = 16.968, p < 0.001). There were also significant differences in plasma BDNF levels of ADHD patients and those of normal controls for males and females (Mann–Whitney U-test, p = 0.001 and 0.041, respectively). We also found a significant correlation between plasma BDNF levels and omission errors in ADS outcome-variable T-scores ( p < 0.001). Conclusions Our study suggests that there is an increase of plasma BDNF levels in untreated ADHD patients, and that plasma BDNF levels had a significant positive correlation with the severity of inattention symptoms. Further studies are required to elucidate the source and role of circulating BDNF in ADHD.

Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: Relationship to glucose metabolism and biomarkers of insulin resistance

Objectives The aims of this study were to measure serum levels of brain-derived neurotrophic factor (BDNF) in patients with type 2 diabetes mellitus (T2DM) and to investigate the association of these BDNF levels with biomarkers of glucose metabolism and insulin resistance. Design and methods We studied 112 patients with T2DM and 80 age- and gender-matched control subjects. Results Serum BDNF levels were significantly lower in patients with T2DM compared to control subjects (15.5 ± 5.2 ng/mL vs. 20.0 ± 7.3 ng/mL, P < 0.01). In patients with T2DM, BDNF levels were significantly higher in females than in males ( P < 0.01). In the female patients, BDNF was positively related to immunoreactive insulin (IRI) ( ρ = 0.458, P < 0.05) and HOMA-R ( ρ = 0.444, P < 0.05). Stepwise multiple regression analysis showed a significant relationship between BDNF and IRI ( F = 5.294, P < 0.05) in female patients with diabetes. Conclusions These findings suggest that BDNF may contribute to glucose metabolism.

Plasma Concentrations of Brain-derived Neurotrophic Factor in Patients Undergoing Minor Surgery: A Randomized Controlled Trial

We measured perioperative plasma concentrations of brain-derived neurotrophic factor (BDNF), a major mediator of synaptic plasticity in the central nervous system, in males, 30-65 years old, undergoing lumbar or cervical discotomy. Patients were randomly allocated to a general anesthetic with propofol induction and maintenance or with thiopental induction and isoflurane maintenance. BDNF plasma concentrations were measured before induction (baseline), 15 min after induction but before start of surgery, at skin closure, in the post-anesthetic care unit, and 24 h postoperatively. Data from 26 patients (13 in each group) were analyzed. At each time point, BDNF plasma concentrations showed large variability. At baseline, concentrations were 631 +/- 337 (mean +/- SD) pg ml(-1) in the propofol group and were 549 +/- 512 pg ml(-1) in the thiopental-isoflurane group (P = 0.31). At 15 min, concentrations significantly decreased in the propofol group (247 +/- 219 pg ml(-1), P = 0.0012 compared with baseline) but remained unchanged in the thiopental-isoflurane group (597 +/- 471 pg ml(-1), P = 0.798 compared with baseline). At skin closure and in the post-anesthetic care unit, concentrations were not different from baseline in both groups. At 24 h, concentrations significantly decreased below baseline in both groups (propofol: 232 +/- 129 pg ml(-1), P = 0.0015; thiopental-isoflurane: 253 +/- 250 pg ml(-1), P = 0.016). In the propofol group, there was a weak but statistically significant positive correlation (R2 = 0.38, P = 0.026) between the duration of surgery and BDNF plasma concentrations at skin closure. These data suggest that in males undergoing elective minor surgery, BDNF plasma concentrations show a specific pattern that is influenced by the anesthetic technique and, possibly, by the duration of surgery.

Decreased levels of serum brain‐derived neurotrophic factor in both depressed and euthymic patients with unipolar depression and in euthymic patients with bipolar I and II disorders

Brain-derived neurotrophic factor (BDNF) has been proposed as a candidate molecule in the pathophysiology of major depressive disorder (MDD) and bipolar disorders (BD). Reduced levels of peripheral BDNF have been found in drug-free MDD patients, in drug-treated depressed or manic patients with BD type I (BD-I), but not in drug-treated euthymic BD-I individuals. No study has been done in patients with BD type II (BD-II). Moreover, the influence of Axis I psychiatric comorbidity on circulating BDNF in affective patients has never been evaluated. Therefore, in the present study, we aimed: (i) to confirm previous findings on peripheral BDNF in MDD and BD-I patients; (ii) to assess whether changes in circulating BDNF occur also in patients with BD-II; and (iii) to exclude the possibility that comorbid psychiatric disorders exerted an effect on BDNF levels in affective patients. We measured serum BDNF concentrations by an enzyme-linked immunosorbent assay method in 85 subjects, including 24 euthymic patients with unipolar depression (UD), 17 euthymic patients with BD-I, 11 euthymic patients with BD-II, 11 UD patients with a current major depressive episode and 22 drug-free healthy controls. At the time of the study, 15 patients were drug-treated; the remaining ones were drug-free for at least four weeks. Compared to healthy controls, serum BDNF concentrations were significantly reduced in all the patient groups (F(4,80) = 3.840, p = 0.006) with no significant difference among them. Drug treatments and comorbid psychiatric disorders had no effect on lowered circulating BDNF levels in affective patients. Present results confirm previous independent findings of reduced circulating BDNF in patients with MDD and report, for the first time, decreased serum BDNF levels in euthymic patients with UD, BD-I and BD-II, independently from drug treatment status and concomitant Axis I psychiatric disorders.

Serum levels of brain-derived neurotrophic factor in patients with schizophrenia and bipolar disorder

There is evidence that major psychiatric discords such as schizophrenia (SZ) and bipolar disorder (BD) are associated with dysregulation of synaptic plasticity with downstream alterations of neurotrophins. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system (CNS), and performs many biological functions such as promoting the survival, differentiation, and plasticity of neurons. Variants in the BDNF gene increase the risk of SZ and bipolar disorder. Chronic administration of drugs used to treat SZ and BD, such as lithium, valproate, quetiapine, clozapine, and olanzapine, increases BDNF expression in rat brain. To examine serum BDNF, three groups of chronically medicated DSM-IV SZ patients, on treatment with clozapine (n=27), typical (n=14), and other atypical antipsychotics (n=19), 30 euthymic BD patients, and 26 healthy control had 5 ml blood samples collected by venipuncture. Serum BDNF levels were significantly higher in SZ patients (p<0.001) when compared to either controls or euthymic BD patients. Increased BDNF in SZ patients might be related to the course of illness or to treatment variables. Prospective studies are warranted.

Decreased plasma BDNF level in depressive patients

Background Recent reports have suggested a pathophysiological role for brain-derived neurotrophic factor (BDNF) in major depressive disorder (MDD). We evaluated plasma levels of BDNF in patients with MDD. Methods Plasma BDNF levels were measured in 77 MDD patients and 95 normal controls. The severity of psychiatric symptoms was measured with the Hamilton Depression Rating Scale and the Brief Psychiatric Rating Scale. Results Plasma BDNF levels were significantly lower in MDD patients than in normal control subjects ( p < 0.001). Plasma BDNF levels were significantly lower in MDD patients with recurrent episodes than in MDD patients with the first episode or normal controls ( p < 0.001). Plasma BDNF levels were significantly lower in non-psychotic MDD patients than in psychotic MDD patients or normal controls ( p < 0.001). Plasma BDNF in suicidal MDD patients were significantly lower than those in non-suicidal MDD patients ( p < 0.001). Limitations We measured only plasma levels of BDNF. However, the cellular sources of BDNF in human plasma are not yet clearly defined. Conclusions Our study suggests that there is a decrease in plasma BDNF levels in untreated MDD patients. However, relapsed or recurrent episodes, suicidal behavior, and psychotic features could also affect the plasma levels of BDNF. Further studies are required to understand the source and role of the circulating BDNF in depression.

Relationship of serum brain-derived neurotrophic factor level with other markers of disease severity in patients with atopic dermatitis

Elevated serum levels of neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been reported in allergic and autoimmune diseases. The aim of this study was to assess serum levels of BDNF in patients with atopic dermatitis (AD) and to investigate the relationship of the BDNF level with other markers of disease severity. Serum BDNF concentration was significantly higher in patients with AD ( n = 62) compared to control subjects ( n = 20) ( P < 0.01). Stepwise multiple regression analysis showed a significant influence of the peripheral blood eosinophil counts ( F = 6.90) and the percentage of CD4 +IL-4 + (Th2) cells ( F = 6.61). Moreover, after remission of AD patients with conventionally treated AD patients ( n = 14), serum levels of BDNF, eosinophil counts and percentage of Th2 cells were decreased significantly. These results suggest that serum BDNF may be a useful marker of disease activity in AD and that both eosinophils and Th2 cells are major cellular sources of serum BDNF.

Reduced serum levels of brain-derived neurotrophic factor in adult male patients with autism

Background The precise mechanisms underlying the pathophysiology of autism are currently unknown. Given the key role of brain-derived neurotrophic factor (BDNF) in brain development, we hypothesized that BDNF may play a role in the pathophysiology of autism. In this study, we studied whether serum levels of BDNF are altered in patients with autism. Methods We measured serum levels of BDNF in 18 adult male patients with autism and 18 age-matched healthy male control subjects. Results The serum levels of BDNF in patients with autism (25.6 ± 2.15 ng/ml (mean ± S.D.)) were significantly ( z = − 4.42, p < 0.001) lower than those of normal controls (61.6 ± 10.9 ng/ml (mean ± S.D.)). Nevertheless, we found no correlations between BDNF levels and clinical variables in autistic patients. Conclusions This study suggests that reduced BDNF levels may play a role in the pathophysiology of autism.

P.1.b.010 Low concentrations of plasma brain-derived neurotrophic factor in patients with panic disorder

P.1.b.010 Low concentrations of plasma brain-derived neurotrophic factor in patients with panic disorder

Brain-Derived Neurotrophic Factor in Patients With Remitted Depression

Brain-Derived Neurotrophic Factor in Patients With Remitted Depression

Reduced plasma levels of NGF and BDNF in patients with acute coronary syndromes

We read with interest the recent article by Manni et al. [1] in which reduced levels of both nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were described in patients with acute coronary syndromes (ACS) compared with healthy controls. BDNF has attracted considerable research interest in recent years, and this neurotropin has been implicated in the pathophysiology of numerous disparate disease states. Although, as stated by the authors, BDNF may indeed be involved in maintaining cardiac homeostasis and have a role in the pathogenesis of human coronary atherosclerosis, the reduced plasma levels of BDNF and NGF reported by Manni et al. may be explained by the stress and hypercortisolaemia associated with ACS. As the authors themselves acknowledge, stress can alter BDNF and NGF expression [1]. This is supported by a wealth of preclinical data which has shown that exogenous corticosteroid administration or stress-induced hypercortisolaemia can cause acute downregulation of BDNF and NGF expression, an effect which is rapidly reversible following removal of the stressor [2]. Both coronary artery disease [3] and myocardial infarction [4] are associated with activation of the hypothalamic–pituitary–adrenal (HPA) axis and raised cortisol levels for at least 24 h post infarction. Given that

Brain-derived neurotrophic factor is increased in atopic dermatitis and modulates eosinophil functions compared with that seen in nonatopic subjects

Recently, the pivotal role of brain-derived neurotrophic factor (BDNF) has been described in allergic asthma. However, the role of this neurotrophin in atopic dermatitis (AD) still remains unknown. The aim of this study was to investigate the functional role of BDNF on eosinophils and to assess BDNF levels in patients with AD and nonatopic control subjects. Methods p75 Neurotrophin receptor and tyrosine kinase B receptor expression was demonstrated by using FACS analysis and immunohistochemistry. BDNF levels were assessed with ELISA and FACS analysis. Chemotactic activity (modified Boyden chamber assay), eosinophil cationic protein release (fluoroenzyme immunoassay), respiratory burst (lucigenin-dependent chemiluminescence), and apoptosis (Nicoletti protocol and Annexin-V method) assays were used to assess BDNF functional activity. BDNF levels were increased in serum, plasma, eosinophils, and supernatants of stimulated eosinophils from patients with AD compared with levels seen in nonatopic control subjects ( P < .05-.001). In addition, p75 neurotrophin receptor and tyrosine kinase B expression was higher on eosinophils from patients with AD compared with that seen on eosinophils from nonatopic control subjects ( P < .05-.001). Eosinophil apoptosis was inhibited by BDNF ( P < .05-.01) and chemotactic index was increased ( P < .001) in BDNF-stimulated eosinophils from patients with AD, whereas this effect was not shown in eosinophils from nonatopic control subjects. However, no response of BDNF through the release of eosinophil cationic protein or reactive oxygen species was found. This study provides the first evidence for a functional role of BDNF on eosinophils from patients with AD, probably mediated by an increased expression of BDNF receptors compared with that seen in nonatopic control subjects. In addition, higher intracellular, serum, and plasma BDNF levels, as well as the release of BDNF by eosinophils, underline the particular importance of BDNF in patients with AD, pointing to new pathophysiologic aspects of this chronic inflammatory skin disease.

Circulating brain-derived neurotrophic factor is decreased in women with anorexia and bulimia nervosa but not in women with binge-eating disorder: relationships to co-morbid depression, psychopathology and hormonal variables

Several lines of evidence indicate a role of the brain-derived neurotrophic factor (BDNF) in the modulation of eating behaviour. Therefore, alterations in the physiology of this neurotrophin may be involved in the pathogenesis of eating disorders. In the present study, we investigated serum levels of BDNF in patients with anorexia nervosa (AN), bulimia nervosa (BN) and binge-eating disorder (BED). Ninety-nine drug-free women (27 with AN, 24 with BN, 24 with BED and 24 healthy controls) underwent both a blood sample collection in the morning and diagnostic and psychopathological assessments by means of structured clinical interviews and ad-hoc rating scales. Serum levels of BDNF, 17 beta-oestradiol, FT3 and FT4 were measured. Compared to healthy controls, serum levels of BDNF were significantly reduced in underweight AN women and in normal weight BN women, but not in overweight BED women. Changes in circulating BDNF levels were not affected by the presence of co-morbid depressive disorders. No significant correlation emerged between neurotrophin concentrations and psychopathological, nutritional, demographic and hormonal variables. These findings evidentiate alterations in serum BDNF levels in malnourished patients with AN or BN, but not in well-nourished individuals with BED. Since BDNF seems to exert a satiety effect, its reduction may represent an adaptive change to counteract the decreased calorie ingestion of AN and BN individuals.

Low serum levels of brain-derived neurotrophic factor in patients with schizophrenia do not elevate after antipsychotic treatment

Brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the etiology of schizophrenia. There is a line of evidence that disruption of neurotrophins could play a role in the etiology of schizophrenia, and antipsychotics show their effect by altering levels of neurotrophins. The aim of this study was to evaluate the effect of antipsychotics on serum BDNF levels and their relationship with the symptoms in patients with schizophrenia. Twenty-two schizophrenia patients were enrolled in the study. The control group consisted of 22 age- and sex-matched physically and mentally healthy volunteers (7 male, 15 female). Serum BDNF levels and the positive and negative syndrome scale (PANSS) scores were recorded at baseline and after 6 weeks of treatment. Serum BDNF levels were also recorded in the control group. Schizophrenia patients who failed to meet 30% improvement in PANSS score were excluded from the study. The baseline serum BDNF levels of schizophrenia patients were lower than those of controls ( t=4.56; df=21; p<0.001). There was no correlation between serum BDNF levels and PANSS scores in patients with schizophrenia ( p>0.05). Although PANSS (for positive symptoms p<0.001, for negative symptoms p<0.001) and general psychopathology ( t=20.9; df=22; p<0.001) scores improved significantly after 6 weeks of antipsychotic treatment; there was no change in BDNF levels in patients' serum ( p>0.05). Our results support the view that BDNF would be associated with schizophrenia. However, we could not conclude that treatment with antipsychotics alters serum BDNF levels in patients with schizophrenia.

Brain-derived neurotrophic factor in patients with multiple sclerosis

The aim of the present research was to verify the production of BDNF by peripheral blood mononuclear cells (PBMCs), unstimulated and stimulated with phytohemagglutinin (PHA), anti-OKT3 Ab and myelin basic protein (MBP), in 35 patients affected by multiple sclerosis (MS), 20 with relapsing–remitting (R-R) MS and 15 with secondary progressive (SP) MS. Seven R-R MS patients were assessed during the attack, in the subsequent recovery phase and also 3 months after relapse. The production of BDNF by PBMCs was also evaluated in 20 age- and sex-matched control subjects. Levels of BDNF were also determined in CSF of both patient groups and 20 control subjects. Results: Levels of BDNF (pg/ml) in the supernatants of unstimulated and PHA-, anti-OKT3 Ab- and MBP-stimulated PBMCs in patients with R-R MS were significantly higher during relapse and in the recovery phase compared with values detected in the stable phase of the disease. Significantly lower BDNF values were found in unstimulated and stimulated PBMC supernatants of patients with SP MS compared to control subjects. This reduction was greater in patients with a 1-point increase in the EDSS score in the last 6 months compared with that in patients without a progression of the disability score. Reduction in the levels of BDNF was also confirmed in the CSF of SP MS patients compared with R-R MS patients assessed during a stable phase of the disease and control subjects. Discussion: On the basis of recent experimental findings, a neuroprotective effect of BDNF produced by inflammatory cells can be hypothesized during relapses in MS. This can favor remyelination. The reduced production of BDNF by PBMCs of patients with SP MS can contribute to the progression of demyelinating disease and axonal loss in this form.

Brain-derived neurotrophic factor in patients with frontotemporal dementia

Brain-derived neurotrophic factor (BDNF) promotes survival and growth of various nerve cell populations during normal development and following different insults in the developing and adult brain. BDNF expression is reduced in Alzheimer disease, but little is known about BDNF expression in other types of dementia. Frontotemporal dementia (FTD) is a common cause of mental impairment in old age, which is characterized by neuron loss in the upper cortical layers mainly of the frontal and temporal cortex. BDNF protein expression has been examined by Western blotting and immunohistochemistry in the cerebral cortex of individuals affected by FTD. Examination of pathological samples ( n=8, mean age: 74.7 years; four men, four women) was conducted in parallel with corresponding samples from age-matched controls ( n=8; mean age: 72.6 years; three men, five women). Post-mortem delay was between 2 and 6 h. Preserved BDNF expression, as revealed by Western blotting, has been observed in the frontal and temporal cortices of patients with FTD. Furthermore, immunohistochemistry has disclosed maintained BDNF immunoreactivity in surviving neurons of the upper cellular layers, as well as in neurons of the inner cellular layers in FTD. These results show that FTD is not associated with a decay of BDNF in cortical neurons, and therefore, that BDNF is differentially regulated in diseases causing dementia.