Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: A systematic review and meta-regression analysis

Fernandes, Brisa S.; Gama, Clarissa Severino; Ceresér, Keila Maria Mendes; Yatham, Lakshmi N.; Fries, Gabriel R.; Colpo, Gabriela D.; Lucena, David Freitas de; Kunz, Maurício; Gomes, Fabiano A.; Kapczinski, Flávio

doi:10.1016/j.jpsychires.2011.03.002

Cited by 357 publications

(248 citation statements)

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“…It is known that neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease and mood disorders, such as depression and schizophrenia, are associated with decreased BDNF levels in affected brain regions, which is paralleled by respective changes of BDNF levels in the blood of patients (Castrén and Rantamäki, 2010a;Castrén and Rantamäki, 2010b;Ciammola et al, 2007;Fernandes et al, 2011;Ferrer et al, 2000;Green et al, 2011;Laske et al, 2007;Sen et al, 2008). However, whether reduced serum BDNF levels in patients with Huntington's disease might serve as a reliable biomarker is still under debate (Zuccato et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Stably BDNF-GFP expressing embryonic stem cells exhibit a BDNF release-dependent enhancement of neuronal differentiation

Leschik

Eckenstaler

Nieweg

et al. 2013

Journal of Cell Science

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SummaryBrain-derived neurotrophic factor (BDNF) is known to be a crucial regulator of neuronal survival and synaptic plasticity in the mammalian brain. Furthermore, BDNF positively influences differentiation of embryonic neural precursors, as well as that of neural stem cells from adult neurogenic niches. To study the impact of cell-released BDNF on neural differentiation of embryonic stem cells (ESCs), which represent an attractive source for cell transplantation studies, we have generated mouse ESC clones overexpressing BDNF-GFP by use of knock-in technology. After neural differentiation in vitro, we observed that ESC clones overexpressing BDNF-GFP gave rise to an increased number of neurons as compared to control ESCs. Neurons derived from BDNF-GFP-expressing ESCs harbored a more complex dendritic morphology and differentiated into the GABAergic lineage more than controls. Moreover, we show that ESC-derived neurons released BDNF-GFP in an activity-dependent manner and displayed similar electrophysiological properties as cortical neurons. Thus, our study describes the generation of ESCs stably overexpressing BDNF-GFP, which are ideally suited to investigate the ameliorating effects of BDNF in cell transplantation studies of various neuropathological conditions.

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Section: Introductionmentioning

confidence: 99%

Stably BDNF-GFP expressing embryonic stem cells exhibit a BDNF release-dependent enhancement of neuronal differentiation

Leschik

Eckenstaler

Nieweg

et al. 2013

Journal of Cell Science

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“…This protein is considered an important neuroplasticity marker and is involved in several processes, such as neuronal differentiation and synaptic plasticity. 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.…”

Section: Metabolic Systems Involved In the Pathophysiology Of Psychiamentioning

confidence: 99%

“…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%

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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“…Estudos subsequentes confirmaram essa observação em pacientes não medicados 43,44 . Embora nem todos os estudos tenham confirmado esse efeito 45 , metanálises mostram um tamanho de efeito bastante robusto 46,47 . Dados longitudinais preliminares ainda indicam que o tratamento bem-sucedido da mania se associa com a normalização dos níveis da neurotrofina 35,48 .…”

Section: Neuroplasticidadeunclassified

Marcadores periféricos e a fisiopatologia do transtorno bipolar

Magalhães¹,

Fries²,

Kapczinski³

2012

Rev. psiquiatr. clín.

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Introdução: O entendimento da fisiopatologia do transtorno bipolar vem tendo avanços consistentes nos últimos anos. Um enfoque na relação entre carga alostática e alterações sistêmicas vem tomando corpo, com o objetivo de se entender a frequente progressão da doença. Proeminentes entre os mediadores periféricos têm sido as moléculas que poderiam ser amplamente agrupadas em neurotrofinas, marcadores de estresse oxidativo e marcadores inflamatórios. Objetivo: Descrever achados recentes em relação à fisiopatologia sistêmica do transtorno bipolar, com enfoque especial em estudos brasileiros, tentando articular uma visão coerente do conhecimento atual do campo. Método: Revisão narrativa da literatura relacionada a neurotrofinas, estresse oxidativo e marcadores inflamatórios no transtorno bipolar. Resultados: Diversas fontes de evidência, provenientes tanto de estudos pré-clínicos quanto clínicos, revelam consistentemente alterações sistêmicas no transtorno bipolar. Os achados são especialmente robustos em pacientes com múltiplos episódios. Nesses, alterações relacionadas a episódios de mania e depressão são notáveis em neurotrofinas e dano oxidativo a lipídeos. Um número menor de estudos mostra alterações no sistema imune, em particular estados pró-inflamatórios. Conclusão: Alterações sistêmicas que correlacionam o transtorno bipolar a comorbidade clínica, disfunção cognitiva, incapacidade e mortalidade precoce começam a ser traçadas. Estudos envolvendo desenhos longitudinais, amostras populacionais e ensaios clínicos envolvendo marcadores periféricos devem ser incorporados no futuro próximo e reforçar a validade de uma noção de envolvimento multissistêmico no transtorno bipolar.Magalhães PVS, et al. / Rev Psiq Clín. 2012;39(2):60-7 Palavras-chave: Transtorno bipolar, inflamação, estresse oxidativo, neurotrofinas, fator neurotrófico derivado do cérebro, fisiopatologia, biomarcadores. ABSTRACT Introduction:The understanding of the pathophysiology of bipolar disorder has steadily advanced in the past few years. Thereby, a focus on allostatic load and systemic changes has appeared, with the aim to understand illness progression. Amongst the peripheral markers, molecules that can be widely classified into neurotrophins, oxidadive stress markers, and inflammation markers have been elevated. Objective: To describe recent findings regarding the systemic pathophysiology of bipolar disorder, with a special focus on Brazilian studies and to create a coherent view of the current knowledge in the field. Method: Narrative review of the literature regarding neurotrophins, oxidative stress, and inflammatory markers in bipolar disorder. Results: A diverse body of evidence, based on both pre-clinical and clinical studies, reveals consistent systemic changes in bipolar disorder. The findings are particularly robust in patients after multiple episodes. Thereby, remarkable changes related to manic and depressive episodes were found in neurotrophins and oxidative damage to lipids. Regarding to immune system alterations, in particular pro...

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Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: A systematic review and meta-regression analysis

Cited by 357 publications

References 45 publications

Stably BDNF-GFP expressing embryonic stem cells exhibit a BDNF release-dependent enhancement of neuronal differentiation

Stably BDNF-GFP expressing embryonic stem cells exhibit a BDNF release-dependent enhancement of neuronal differentiation

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

Marcadores periféricos e a fisiopatologia do transtorno bipolar

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