Brain-derived neurotrophic factor serum levels before and after treatment for acute mania

Molecular Psychiatry Laboratory, Hospital de Clinicas de Porto Alegre, Brazil.
Neuroscience Letters (Impact Factor: 2.03). 04/2009; 452(2):111-3. DOI: 10.1016/j.neulet.2009.01.028
Source: PubMed


Accumulating evidence suggests that reduced levels of brain-derived neurotrophic factor (BDNF) in acute mood episodes may play an important role in the pathophysiology of bipolar disorder (BD). In order to assess changes in BDNF serum levels in BD patients before and after treatment for acute mania, ten bipolar patients were prospectively examined at inpatient unit admission and discharge. Diagnoses were made using the Structured Clinical Interview for DSM-IV, SCID-I. Serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF levels were decreased in BD patients during mania when compared to controls (p=0.013) but this difference was no longer significant after treatment (p=0.126). A sharp increase in BDNF levels was found after treatment of the episode of acute mania (p=0.010). These findings suggest that the changes in BDNF serum levels may be associated with treatment response in acute mania. Further studies designed to validate the use of BDNF as a marker of treatment response in bipolar disorder are warranted.

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Available from: Flavio Kapczinski,
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    • "BDNF (Brain Derived Neurotrophic Factor), the most widely studied trophic factor is a key mediator for synaptic efficacy, neuronal connectivity and neuroplasticity, and the regulation of neuronal survival and control the activity of many neurotransmitter systems (Cotman and Berchtold, 2002; Duman et al., 2000). It was consistently shown to be decreased during manic, depressive (Cunha et al., 2006; Fernandes et al., 2011; Kapczinski et al., 2008; Lin, 2009; Machado-Vieira et al., 2007; Palomino et al., 2006; Tramontina et al., 2009) and even in euthymic states (Kauer- Sant'anna et al., 2008; Lin, 2009; Monteleone et al., 2008) of bipolar disorder. Glial cells have an important role in providing trophic support to neuron's metabolism and the formation of the synapsis as the third-partner in synaptic transmission (tripartite synapse) (Araque et al., 1999; Sawada et al., 2000). "
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    ABSTRACT: Objective Brain-derived neurotrophic factor (BDNF) has been consistently reported to be decreased in mania or depression in bipolar disorders. Evidence suggests that Glial cell line-derived neurotrophic factor (GDNF) has a role in the pathogenesis of mood disorders. Whether GDNF and BDNF act in the same way across different episodes in bipolar disorders is unclear. Method BDNF and GDNF serum levels were measured simultaneously by enzyme-linked immunosorbent assay (ELISA) method in 96 patients diagnosed with bipolar disorder according to DSM-IV (37 euthymic, 33 manic, 26 depressed) in comparison to 61 healthy volunteers. SCID- I and SCID-non patient version were used for clinical evaluation of the patients and healthy volunteers respectively. Correlations between the two trophic factor levels, and medication dose, duration and serum levels of lithium or valproate were studied across different episodes of illness. Results Patients had significantly lower BDNF levels during mania and depression compared to euthymic patients and healthy controls. GDNF levels were not distinctive. However GDNF/BDNF ratio was higher in manic state compared to euthymia and healthy controls. Significant negative correlation was observed between BDNF and GDNF levels in euthymic patients. While BDNF levels correlated positively, GDNF levels correlated negatively with lithium levels. Regression analysis confirmed that lithium levels predicted only GDNF levels positively in mania, and negatively in euthymia. Limitations Small sample size in different episodes and drug-free patients was the limitation of thestudy. Conclusion Current data suggests that lithium exerts its therapeutic action by an inverse effect on BDNF and GDNF levels, possibly by up-regulating BDNF and down-regulating GDNF to achieve euthymia.
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    • "Furthermore, clinical recovery is associated with a corresponding increase in BDNF levels [38]. The pathophysiological role of BDNF BD has been reviewed in detail elsewhere [38] [39]. Several effective treatments for BD, such as lithium, electroconvulsive therapy and atypical antipsychotics are known to increase BDNF levels [40] [41] [42]. "
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    ABSTRACT: Curcumin is a polyphenolic nonflavonoid compound extracted from the rhizome of turmeric (Curcuma longa), a plant commonly used in Indian and Chinese traditional medicine to treat rheumatism, cough, inflammation and wounds. Curcumin putative targets, known based on studies of diverse central nervous system disorders other than bipolar disorders (BD) include several proteins currently implicated in the pathophysiology of BD. These targets include, but are not limited to, transcription factors activated by environmental stressors and pro-inflammatory cytokines, protein kinases (PKA, PKC), enzymes, growth factors, inflammatory mediators, and anti-apoptotic proteins (Bcl-XL). Herein, we review previous studies on the anti-inflammatory and anti-oxidant properties of curcumin and discuss its therapeutic potential in BD.
    Medical Hypotheses 02/2013; 80(5). DOI:10.1016/j.mehy.2013.02.001 · 1.07 Impact Factor
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    • "One study reported significantly decreased mRNA levels of lymphocyte-derived BDNF and decreased protein BDNF levels in platelets in manic unmedicated children and adolescents versus controls (Pandey et al., 2008). Two independent longitudinal studies conducted with manic patients found that peripheral BDNF levels increase after successful pharmacological treatment (de Sousa et al., 2011; Tramontina et al., 2009). In a recent systematic review of 13 studies including a total of 1113 subjects, Fernandes et al. (2011) found that BDNF levels were consistently reduced during manic and depressive episodes, but not during euthymia, and increased after treatment for acute mania. "
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    ABSTRACT: Although the etiology of bipolar disorder remains uncertain, multiple studies examining neuroimaging, peripheral markers and genetics have provided important insights into the pathophysiologic processes underlying bipolar disorder. Neuroimaging studies have consistently demonstrated loss of gray matter, as well as altered activation of subcortical, anterior temporal and ventral prefrontal regions in response to emotional stimuli in bipolar disorder. Genetics studies have identified several potential candidate genes associated with increased risk for developing bipolar disorder that involve circadian rhythm, neuronal development and calcium metabolism. Notably, several groups have found decreased levels of neurotrophic factors and increased pro-inflammatory cytokines and oxidative stress markers. Together these findings provide the background for the identification of potential biomarkers for vulnerability, disease expression and to help understand the course of illness and treatment response. In other areas of medicine, validated biomarkers now inform clinical decision-making. Although the findings reviewed herein hold promise, further research involving large collaborative studies is needed to validate these potential biomarkers prior to employing them for clinical purposes. Therefore, in this positional paper from the ISBD-BIONET (biomarkers network from the International Society for Bipolar Disorders), we will discuss our view of biomarkers for these three areas: neuroimaging, peripheral measurements and genetics; and conclude the paper with our position for the next steps in the search for biomarkers for bipolar disorder.
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