Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes

Cunha, Ângelo Batista Miralha da; Frey, Benício N.; Andreazza, Ana Cristina; Goi, Júlia Domingues; Rosa, Adriane Ribeiro; Gonçalves, Carlos Alberto; Santin, Ana Paula; Kapczinski, Flávio

doi:10.1016/j.neulet.2005.12.085

Cited by 353 publications

(224 citation statements)

References 23 publications

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“…These kinases include protein kinase A (PKA), [24][25][26] protein kinase C (PKC), 27 p38 and p44 mitogen-activated protein kinases (MAPK), 28,29 and Ca 2 þ -calmodulin kinase (CaMK) IV. 30 Of relevance to bipolar disorder, BDNF levels are decreased in the serum, 31 and BDNF and phosphorylated CREB levels are decreased in the brain of bipolar patients compared to controls. 32,33 A Val66Met polymorphism in the BDNF gene confers susceptibility to bipolar disorder in humans [34][35][36] and a BDNF-linked complex polymorphic region, which has lower transcriptional activity than other alleles in rat primary cultured neurons, also confers susceptibility to bipolar disorder in humans.…”

Section: Introductionmentioning

confidence: 99%

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

et al. 2006

Mol Psychiatry

258

151

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Decreased docosahexaenoic acid (DHA) and brain-derived neurotrophic factor (BDNF) have been implicated in bipolar disorder. It also has been reported that dietary deprivation of n-3 polyunsaturated fatty acids (PUFAs) for 15 weeks in rats, increased their depression and aggression scores. Here, we show that n-3 PUFA deprivation for 15 weeks decreased the frontal cortex DHA level and reduced frontal cortex BDNF expression, cAMP response element binding protein (CREB) transcription factor activity and p38 mitogen-activated protein kinase (MAPK) activity. Activities of other CREB activating protein kinases were not significantly changed. The addition of DHA to rat primary cortical astrocytes in vitro, induced BDNF protein expression and this was blocked by a p38 MAPK inhibitor. DHA's ability to regulate BDNF via a p38 MAPK-dependent mechanism may contribute to its therapeutic efficacy in brain diseases having disordered cell survival and neuroplasticity.

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Section: Introductionmentioning

confidence: 99%

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

et al. 2006

Mol Psychiatry

258

151

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“…Family-based association studies show that the Val66Met polymorphism is associated with the diagnosis of BD and the phenomenon of rapid cycling (Green et al, 2006;Lohoff et al, 2005) and early age of illness onset (Tang et al, 2008) in BD patients, albeit some other studies did not show this association (Gratacos et al, 2007;Kanazawa et al, 2007;Kunugi et al, 2004). Moreover, both BD and major depressive disorder (MDD) patients show decreased serum levels of BDNF (Cunha et al, 2006;Karege et al, 2004;Machado-Vieira et al, 2007) compared to healthy subjects, and there is an inverse correlation between BDNF levels and severity of the depressive (Karege et al, 2004;MachadoVieira et al, 2007;Shimizu et al, 2003) and manic states (Cunha et al, 2006). A magnetic resonance study demonstrated that serum BDNF levels are positively associated with the concentration of N-acetyl aspartate, a marker of neuronal integrity, and choline, a marker of cell membrane turnover, in the anterior cingulate cortex (ACC) (Lang et al, 2007), suggesting that peripheral BDNF content may be a potential marker of cerebral cortical integrity.…”

Section: Introductionmentioning

confidence: 99%

Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

Matsuo

Walss‐Bass

Nery

et al. 2009

Neuropsychopharmacol

112

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The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been proposed as a possible candidate for involvement in the pathophysiology of bipolar disorder (BD). To determine whether an association exists between the BDNF Val66Met genotype and morphometric abnormalities of the brain regions involved in memory and learning in BD and healthy subjects. Forty-two BD patients and 42 healthy subjects were studied. Interactions between BDNF Val66Met genotype and diagnosis in gray (GM) volumes were analyzed using an optimized voxel-based morphometry technique. Declarative memory function was assessed with the California Verbal Learning Test II. Left and right anterior cingulate GM volumes showed a significant interaction between genotype and diagnosis such that anterior cingulate GM volumes were significantly smaller in the Val/Met BD patients compared with the Val/Val BD patients (left P ¼ 0.01, right P ¼ 0.01). Within-group comparisons revealed that the Val/Met carriers showed smaller GM volumes of the dorsolateral prefrontal cortex compared with the Val/Val subjects within the BD patient (P ¼ 0.01) and healthy groups (left P ¼ 0.03, right P ¼ 0.03). The Val/ Met healthy subjects had smaller GM volumes of the left hippocampus compared with the Val/Val healthy subjects (Po0.01). There was a significant main effect of diagnosis on memory function (P ¼ 0.04), but no interaction between diagnosis and genotype was found (P ¼ 0.48). The findings support an association between the BDNF Val66Met genotype and differential gray matter content in brain structures, and suggest that the variation in this gene may play a more prominent role in brain structure differences in subjects affected with BD.

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“…71 Altered BDNF levels and genetic expression are well documented in schizophrenia 12 and BD, 72,73 and are associated with episodes as well as with length of illness. 12,13,73 Interestingly, BDNF has also been implicated in energy metabolism. 74 The Val66Met polymorphism of the BDNF gene is associated with a higher body mass index (BMI) in healthy individuals.…”

Section: Metabolic Systems Involved In the Pathophysiology Of Psychiamentioning

confidence: 99%

“…Reductions in neurotrophins, such as brain-derived neurotrophic factor (BDNF), have been repeatedly demonstrated in schizophrenia 12 and BD both during mood episodes and in periods of euthymia. 13 Similarly, altered peripheral levels of mediators involved in the regulation of neuroplasticity, such as factors of apoptosis and inflammation markers, have been documented in schizophrenia 14,15 and in BD. [16][17][18] Recently, several authors have proposed that schizophrenia and BD are progressive in nature, with substantial differences between early and late stages in terms of clinical presentation, treatment response, and neurobiological characteristics.…”

Section: Introductionmentioning

confidence: 99%

The "selfish brain" hypothesis for metabolic abnormalities in bipolar disorder and schizophrenia

Mansur

Brietzke

2012

Trends Psychiatry Psychother.

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A hipótese do "cérebro egoísta" para alterações metabólicas no transtorno bipolar e na esquizofreniaThe "selfish brain" hypothesis for metabolic abnormalities in bipolar disorder and schizophrenia AbstractMetabolic abnormalities are frequent in patients with schizophrenia and bipolar disorder (BD), leading to a high prevalence of diabetes and metabolic syndrome in this population. Moreover, mortality rates among patients are higher than in the general population, especially due to cardiovascular diseases. Several neurobiological systems involved in energy metabolism have been shown to be altered in both illnesses; however, the cause of metabolic abnormalities and how they relate to schizophrenia and BD pathophysiology are still largely unknown. The "selfish brain" theory is a recent paradigm postulating that, in order to maintain its own energy supply stable, the brain modulates energy metabolism in the periphery by regulation of both allocation and intake of nutrients. We hypothesize that the metabolic alterations observed in these disorders are a result of an inefficient regulation of the brain energy supply and its compensatory mechanisms. The selfish brain theory can also expand our understanding of stress adaptation and neuroprogression in schizophrenia and BD, and, overall, can have important clinical implications for both illnesses. Keywords: Schizophrenia, bipolar disorder, metabolism, brain metabolism, stress, allostasis. ResumoAlterações metabólicas são frequentes em pacientes com esquizofrenia e transtorno bipolar (TB), levando a uma alta prevalên-cia de diabetes e síndrome metabólica nessa população. Além disso, as taxas de mortalidade entre pacientes são mais altas do que na população geral, especialmente em decorrência de doenças cardiovasculares. Vários sistemas neurobiológicos envolvidos no metabolismo energético têm demonstrado alterações nas duas doenças; no entanto, a causa das alterações metabó-licas e a forma como elas se relacionam com a fisiopatologia da esquizofrenia e do TB ainda são arenas em grande parte desconhecidas. A teoria do "cérebro egoísta" é um paradigma recente que postula que, para manter estável seu próprio fornecimento de energia, o cérebro modula o metabolismo da energia na periferia regulando tanto a alocação quanto a ingestão de nutrientes. Apresentamos neste artigo a hipótese de que as alterações metabólicas observadas nesses transtornos são resultado de uma regulação ineficiente do fornecimento de energia do cérebro e seus mecanismos compensatórios. A teoria do cérebro egoísta também pode expandir nosso entendimento sobre a adaptação ao estresse e a neuroprogressão na esquizofrenia e no TB, e, acima de tudo, pode ter implicações clínicas importantes para as duas doenças. Descritores: Esquizofrenia, transtorno bipolar, metabolismo, metabolismo cerebral, estresse, alostase.

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Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes

Cited by 353 publications

References 23 publications

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

The "selfish brain" hypothesis for metabolic abnormalities in bipolar disorder and schizophrenia

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