Serum BDNF Levels Research Articles

The effect of depression, BDNF gene val66met polymorphism and gender on serum BDNF levels

Objective To determine the effect of BDNF gene val66met polymorphism on serum BDNF levels in drug-free patients with major depressive disorder (MDD) and healthy subjects, that differ by gender. Methods Sixty-six drug-free patients (19 males + 47 females) with non-psychotic MDD and fifty-six healthy controls (18 males + 38 females) were recruited. Three-way ANOVA was employed to analyze the effect of mental health status, met-carriage and gender on Hamilton Depression Rating Scale (HDRS) scores and serum BDNF levels, by using the MIXED Procedure (SAS). Results Patients had a lower serum BDNF level than healthy subjects (22.47 vs. 27.49; p < 0.0001). Met-carrier patients had a higher HDRS score than Val homozygote's (25.99 vs. 22.99, p < 0.02). Serum BDNF level for met-carrier subjects (patients + controls) was lower than Val homozygote subjects (23.08 vs. 26.87; p < 0.002). However, there were no effects of two-way interactions of met-carriage and mental health status on HDRS scores and serum BDNF levels. There was no gender effect on HDRS scores in the patients. Overall, male subjects (patients + controls) had a higher serum BDNF level than female subjects (26.87 vs. 23.08; p < 0.002). However, there were no effects of two-way interactions of gender with mental health status and met-carriage on serum BDNF levels. Conclusions We replicated the previous findings of lower serum BDNF levels during depression and in females. In addition, we found that met-carriage had an effect in reducing serum BDNF levels, regardless of gender and depression. Further animal and human studies with a larger sample size should investigate whether BDNF val66met polymorphism could alter brain and serum BDNF levels.

Alzheimer'S disease (ad) and mild cognitive impairment (mci) patients are characterized by increased bdnf serum levels

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline with loss of memory. In the last years there has been a great interest on the early phases of AD, trying to identify the pathogenic mechanisms of AD and define early treatment modalities. In particular, Mild Cognitive Impairment (MCI) is attractive because it represents a transitional state between normal aging and dementia, although not all MCI patients automatically convert to AD. The neurotrophin brain-derived neurotrophic factor (BDNF) is critical for survival and function of neurons that degenerate in AD and represents a potential neuroprotective agent. However, opposite data on serum levels of BDNF have been reported in AD patients, probably reflecting differences in patient recruitment and stage of the disease. Thus, in this study we measured BDNF serum levels in AD patients (with different degree of severity), MCI patients and healthy subjects. We found that serum BNDF levels were significantly increased in MCI and AD patients when compared to healthy subjects and this increase in AD patients was neither dependent on illness severity, nor on treatment with Acetyl- cholinesterase inhibitors and/or antidepressant medications. Our findings indicate that BDNF serum levels increase in MCI and AD patients, supporting the hypothesis of an upregulation of BDNF in both preclinical phase of dementia (MCI) and clinical stages of AD. Other studies are necessary to establish a direct link between BDNF peripheral levels and AD longitudinal course, as well as the role of other fac- tors, such as blood cell activation, in determining these events.

Serum brain-derived neurotrophic factor in bipolar and unipolar depression: A potential adjunctive tool for differential diagnosis

The differential diagnosis of Bipolar Disorder (BD) and Major Depressive Disorder (MDD) is a diagnostic challenge during depressive episodes. Noteworthy, the proper differentiation between BD depressive state and MDD has important treatment implications. BDNF levels may be valuable adjunctive tool for this differential diagnosis. Ten subjects with MDD, forty with BD type I and thirty healthy comparison subjects were recruited. All subjects had BDNF serum levels measured and, in patients, BDNF serum levels were assessed during acute depressive episode. Optimal sensitivity and specificity of serum BDNF for the differential diagnosis of unipolar and bipolar depression were determined by the receiver operating characteristic (ROC) curve analysis, using a nonparametric approach. Serum BDNF levels in depressive BD patients were lower compared to MDD patients and controls (0.15 ± 0.08, 0.35 ± 0.08, and 0.38 ± 0.12, respectively, p < 0.001). The area under the curve (AUC) of the ROC analysis in BD depression vs. MDD was 0.95 (ranged from 0.89 to 1.00). Overall, the AUC of the ROC analysis (BD depression vs. MDD and controls) was 0.94 (95% CI 0.89 to 0.99, p < 0.001). A proposed “best” cutoff of 0.26 resulted in 88% sensitivity and 90% specificity. Serum BDNF levels appear as a promising tool to discriminate bipolar from unipolar depression. Our results suggest the role of BDNF as an adjunctive tool to promote prompt and accurate diagnosis of BD. However, further investigation and replication of these results are warranted.

Decreased brain-derived neurotrophic factor in medicated and drug-free bipolar patients

Bipolar disorder (BD) has been associated with abnormalities in neuroplasticity and previous studies suggest an important role for BDNF in the pathophysiology of BD. The confounding effect of the use of medication in these studies has been considered a limitation. Thus, studies with both drug-free and medicated patients are necessary to assess the role of medication in serum BDNF levels. Twenty-two manic and depressed drug-free and 22 medicated BD type I patients were matched to 22 controls according to sex and age in a cross-sectional study. BDNF serum levels were assessed using sandwich-ELISA. Serum BDNF levels in drug-free (0.23 ± 0.09), and medicated (0.29 ± 0.19) BD patients were decreased when compared to controls (0.40 ± 0.12) – drug-free/medicated vs. control p < 0.001. The BDNF levels did not differ between medicated and drug-free BD patients. When analyzing patients according to mood states, serum BDNF levels were lower in BD patients during both manic (0.28 ± 0.11) and depressive episodes (0.22 ± 0.17), as compared with healthy controls (0.40 ± 0.12) – manic/depressed patients vs. controls p < 0.001. Results suggest that the association of lower serum BDNF and BD mood episodes is kept even in medicated patients, which strengthens the notion that BDNF serum levels may be considered a biomarker of mood episodes in BD.

Effects of fluoxetine and venlafaxine on serum brain derived neurotrophic factor levels in depressed patients

Background Several studies demonstrated that depressed patients had low serum BDNF levels which correlated with the severity of their depression, and antidepressant treatment increases levels of serum BDNF in depressed patients. It was speculated that agents acting on both noradrenergic and serotonergic transporters might have a greater influence on BDNF levels. The aim of our study was to determine effects of venlafaxine vs. fluoxetine on serum BDNF levels in depressive patients. Methods Forty-three patients diagnosed as major depressive disorder according to DSM-IV are included in the study. Forty-three patients were randomized to take fluoxetine (22 cases) or venlafaxine (21 cases). Serum levels of BDNF were measured by ELISA at baseline and 6 weeks after the start of treatment. Results Baseline levels of BDNF were not significantly different between the patient group and the controls. But male patients and the male controls showed statistical differences with respect to baseline BDNF levels. BDNF levels of the patient group did not change with treatment. Yet, the increase of BDNF levels was close to statistically significant in the fluoxetine group, whereas not significant in the venlafaxine group. There were no significant differences in baseline and 6th week BDNF levels between the responders and the non-responders. Conclusion Further studies controlling for a wide variety of confounding variables are needed, which may help to reach a clear conclusion about the potential of BDNF as a biomarker for depression or as a predictor of antidepressant efficacy.

Addition of risperidone to sertraline improves sertraline‐resistant refractory depression without influencing plasma concentrations of sertraline and desmethylsertraline

In the present study, we examined the efficacy of risperidone addition on sertraline-resistant depressed patients and the effects of risperidone on the metabolism of sertraline. Ten patients (M/F: 4/6, age: 54 +/- 10 years) met the DSM-IV criteria for major depressive disorder enrolled the study. Hamilton Dating Scale for Depression (HAM-D) scores (mean +/- SD) in all 10 patients significantly decreased from 19 +/- 4 (before risperidone addition) to 11 +/- 3 (4 weeks after risperidone addition). Plasma levels of sertraline and desmethylsertraline did not change after risperidone addition. Serum BDNF levels in responders to risperidone addition were changed from 8.1 +/- 2.7 ng/ml (before risperidone addition) to 11.5 +/- 0.9 ng/ml (4 weeks after risperidone addition); in contrast, those in nonresponders changed from 7.8 +/- 2.2 ng/ml (before risperidone addition) to 7.9 +/- 2.4 ng/ml (4 weeks after risperidone addition). These results suggest that the addition of risperidone to sertraline is effective and well tolerated for sertraline-resistant depressive patients, which is accompanied with the increase in serum BDNF levels in responders to the risperidone addition, and the addition of risperidone to sertraline does not seem to influence sertraline metabolism.

Brain-derived neurotrophic factor and neuroplasticity in bipolar disorder

Initial descriptions of bipolar disorder (BD) emphasized that patients returned to a baseline condition after acute episodes. Such definitions were operational in teasing bipolar disorder apart from schizophrenia, where patients were described to be permanently impaired after the initial episodes. However, this view of BD as a disorder where cognition and overall functioning was spared has been changing after the scrutiny of new research. Currently, the cognitive impairment and neuroanatomical changes related to cumulative mood episodes, particularly manic episodes, are well described. In terms of neuropathological findings, recent data suggest that changes in neuronal plasticity, particularly in cell resilience and connectivity, are the main findings in BD. Data from differential lines of research converge to BDNF as an important contributor to the pathophysiology of BD. Serum BDNF levels have been shown to be decreased in depressive and manic episodes, returning to normal levels in euthymia. Moreover, factors that negatively influence the course of BD, such as life stress and trauma, have been shown to be associated with a decrease in serum BDNF levels among bipolar patients. These findings suggest that BDNF plays a central role in the transduction of psychosocial stress and recurrent episodes into the neurobiology of bipolar disorder. The present review discusses the role of BDNF as a mediator of the neuroplastic changes that occur in portion with mood episodes and the potential use of serum BDNF as a biomarker in BD.

Serum levels of brain-derived neurotrophic factor in schizophrenia on a hypocaloric diet

Dietary factors influence BDNF in animal studies, but there is no comparable data in clinical populations. We examined the effect of a dietary intervention on BDNF serum levels in 67 DSM-IV schizophrenic outpatients (51 males and 16 females). Two groups were assessed in a cross-sectional study: one on a hypocaloric diet (HD) and the other not on a hypocaloric diet. Weight, height and BMI data were collected concurrently with 5-ml blood sampling of each subject. BDNF levels were measured with a sandwich-ELISA. The blood sample was obtained a minimum of one month after the exposure to dietary intervention. Serum BDNF levels were significantly higher in patients on the HD ( p = 0.023). Additional research examining the interaction among patterns of nutritional food behavior and underlying physiopathology may result in insights upon which evidence-based decisions regarding dietary interventions can be made in people identified with major psychiatric disorders, such as schizophrenia.

Commentary: Aβ (1–42) injection causes memory impairment, lowered cortical and serum BDNF levels, and decreased hippocampal 5-HT 2A levels

Commentary: Aβ (1–42) injection causes memory impairment, lowered cortical and serum BDNF levels, and decreased hippocampal 5-HT 2A levels

A Pilot Study to Explore the Usefulness of Antibody Array in Childhood Atopic Dermatitis

The pathophysiology of childhood atopic dermatitis (AD) involves complex interactions among cellular, humoral, cytokine and chemokine systems. To evaluate protein expressions using antibody microarray. Severity-nine proteins were assayed using antibody microarray on AD patients age < 18 years. Disease severity was assessed with the SCORing Atopic Dermatitis (SCORAD) and Nottingham Eczema Severity Score (NESS), and quality of life with the Children Dermatology Life Quality Index (CDLQI). Serum IgE levels were also assessed. Normal subjects without atopy were used as controls. Cytokines, chemokines and a wide array of proteins were assayed with RayBio Human Cytokine Antibody Array V (RayBiotech, Norcross, GA). Nine Chinese children with AD and four normal subjects were recruited. The median SCORAD was 60.7. Among the 79 proteins, the levels of BDNF, Fit-3 ligand, IL-8, IL-16, LIGHT, MIP-1beta, MIP-3alpha, NAP-2, PARC, TGF-beta2 and TIMP-2 were significantly different from the controls. Nevertheless, no significance was found when adjusted for multiple comparisons using p = 0.0006. Some of these markers showed significant correlations with various components of SCORAD, NESS and CDLQI. The serum IgE level as a marker of atopy correlates significantly with BDNF, LIGHT, PARC and TIMP-2. The serum levels of BDNF, LIGHT, PARC and TIMP-2 correlate to IgE as a marker of atopy. Although targeting chemokines and chemokine receptors may offer new opportunities for therapeutic interventions in AD, protein assay with cytokine antibody array was generally not helpful in identifying specific molecules pertinent to AD activity.

Reducing medical comorbidity in obese refractory bipolar patients: A descriptive study of adjunctive topiramate in obese patients with bipolar disorder

The aim of this study was to evaluate the impact of psychoeducation in serum levels of BDNF, NGF and GDNF in young adults presenting bipolar disorder (BD). This is a randomized clinical trial including 39 young adults (18–29 years) diagnosed with BD through the Structured Clinical Interview for DSM-IV (SCID-CV). Participants were randomized in two treatment groups: usual treatment (medication) and combined intervention (medication plus psychoeducation). Depressive symptoms were assessed using the Hamilton Depression Rating Scale (HDRS) and severity of manic and hypomanic symptoms was evaluated through the Young Mania Rating Scale (YMRS). The serum levels of trophic factors were measured with an ELISA kit. In both intervention groups, there was an improvement in depressive symptoms significantly between baseline and post-intervention. In the combined intervention, GDNF serum levels increased significantly from baseline to post-intervention. However, there were no differences in BDNF and NGF serum levels. In the usual treatment group, no changes were observed in serum levels of GDNF, BDNF, and NGF the post-intervention in individuals. Our data suggests that only combined intervention was effective in improving depressive symptoms and increasing GDNF levels in a sample of young adults with bipolar disorder.

Reduced serum BDNF levels in patients with chronic schizophrenic disorder in relapse, who were treated with typical or atypical antipsychotics

Reduced serum BDNF levels in patients with chronic schizophrenic disorder in relapse, who were treated with typical or atypical antipsychotics

P2-015: Memory impairment after intrahippocampal Aβ(1-42) injection is accompanied by changes in serum BDNF and hippocampal 5-HT2A receptor levels

P2-015: Memory impairment after intrahippocampal Aβ(1-42) injection is accompanied by changes in serum BDNF and hippocampal 5-HT2A receptor levels

Decreased BDNF in serum of patients with chronic schizophrenia on long-term treatment with antipsychotics

Accumulating evidence suggests BDNF as a molecule involved in the pathophysiology of schizophrenia. To examine the BDNF levels and the relationship between BDNF levels and psychopathology in patients with schizophrenia, 81 physically healthy patients with schizophrenia were compared with 45 age-, sex- matched normal controls. The psychopathology of patients were assessed by the Positive and Negative Syndrome Scale (PANSS). Serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF-like immunoreactivity were significantly lower in medicated patients with chronic schizophrenia than in healthy control subjects. A significant negative correlation between BDNF-like immunoreactivity and PANSS negative subscore was observed. As compared with normal controls, there was a significant decrease in BDNF-like immunoreactivity in patients treated with both atypical and typical antipsychotics. However, no correlation between standardized drug doses and BDNF-like immunoreactivity was found. These findings suggest that serum BDNF levels in chronic schizophrenia under antipsychotic medication may be decreased. However, long-term effects of antipsychotics remain to be characterized.

P.6.057 Serum BDNF levels in conversion disorder:A comparative study with depression

P.6.057 Serum BDNF levels in conversion disorder:A comparative study with depression

P.1.216 Lamotrigine but not lithium prevents or delays depressive episodes in bipolar I disorder

The aim of this study was to evaluate the impact of psychoeducation in serum levels of BDNF, NGF and GDNF in young adults presenting bipolar disorder (BD). This is a randomized clinical trial including 39 young adults (18–29 years) diagnosed with BD through the Structured Clinical Interview for DSM-IV (SCID-CV). Participants were randomized in two treatment groups: usual treatment (medication) and combined intervention (medication plus psychoeducation). Depressive symptoms were assessed using the Hamilton Depression Rating Scale (HDRS) and severity of manic and hypomanic symptoms was evaluated through the Young Mania Rating Scale (YMRS). The serum levels of trophic factors were measured with an ELISA kit. In both intervention groups, there was an improvement in depressive symptoms significantly between baseline and post-intervention. In the combined intervention, GDNF serum levels increased significantly from baseline to post-intervention. However, there were no differences in BDNF and NGF serum levels. In the usual treatment group, no changes were observed in serum levels of GDNF, BDNF, and NGF the post-intervention in individuals. Our data suggests that only combined intervention was effective in improving depressive symptoms and increasing GDNF levels in a sample of young adults with bipolar disorder.