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.
    Full-text · Article · Sep 2014 · Journal of Affective Disorders
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    • "NGF, another member of neurotrophin family has a relevant role in neurogenesis, neuronal plasticity and signaling of different cells of the human immune system (Berry et al., 2012). Studies have shown lower serum BDNF and NGF concentrations in many affective disorders including bipolar disorder (Lin, 2009; Barbosa et al., 2011a), major depressive disorder (Brunoni et al., 2008), manic depression (Tramontina et al., 2009) and obsessive compulsive disorder (Maina et al., 2010). In most of the studies serum concentrations of these neurotrophins have been shown to correlate negatively with severity of the disease (Satomura et al., 2011; Teixeira et al., 2010). "
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    ABSTRACT: BACKGROUND: Brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3) and glial cell line derived neurotrophic factor (GDNF) play critical role in growth, differentiation, maintenance and synaptic plasticity in neuronal systems which is more relevant in adolescence. The present study was undertaken to verify the 'neurotrophin hypothesis' in adolescent depression by (i) comparing serum concentrations of neurotrophic factors in depression patients and healthy control, and (ii) analyzing correlations between clinical severity and serum neurotrophin levels. METHODS: Eighty four adolescent (aged 13-18 years) depressed patients (56 males; 60 medication free/naive) and 64 healthy controls (39 males) were recruited. Severity of depression was measured by Beck's depression inventory, and anxiety by state-trait anxiety inventory. Measurement of serum neurotrophins was done by ELISA. RESULTS: Adolescents with depression had significantly lower levels of BDNF: mean diff. (95% C.I.): 2093.9 (1074.0, 3113.9), NGF: 813.3 (343.1, 1283.6) and GDNF: 158.8 (77.2, 240.4) compared to controls. On gender based analysis female controls had significantly increased trait anxiety scores [-1.1 (-1.8, -0.1)], as compared to control males. In the patient group, female patients had far lower level of NGF: 919.6 (210.9, 1628.3) and NT-3: 1288.8 (145.4, 2432.3) compared to male. BDI-II score showed a statistically significant (p<0.01) negative correlation with all four neurotrophins in male patients while in female patients such negative correlation was observed only with NGF and GDNF (p<0.01). LIMITATIONS: The study is cross-sectional from a tertiary care hospital. CONCLUSION: The novelty of the study lies in its large number of exclusively adolescent depression patients showing significant reduction of BDNF, NGF and GDNF serum levels as compared to controls. A gender bias with much reduction in female has also been recorded.
    Full-text · Article · Jun 2013 · Journal of Affective Disorders
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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.
    Full-text · Article · Feb 2013 · Medical Hypotheses
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