The concept of staging in bipolar disorder: the role of BDNF and TNF-alpha as biomarkers

Kapczinski, Flávio; Fernandes, Brisa S.; Kauer-Sant’Anna, Márcia; Gama, Clarissa Severino; Yatham, Lakshmi N.; Berk, Michael

doi:10.1111/j.1601-5215.2009.00410.x

Cited by 31 publications

(24 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…If future studies reveal an increase in subjects with SZ right before exacerbations of positive symptoms, and that it increases predicts the occurrence of exacerbations of the disorder, this would possibly make CRP a very useful biomarker to guide strategies in the clinical setting. [67][68][69][70][71] Whether an increase in CRP or an improvement of positive symptoms occurs first is unknown. This is a pivotal point and needs further studies in order to clarify the possible role of CRP in the mechanism of action of antipsychotics.…”

Section: Discussionmentioning

confidence: 97%

C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications

et al. 2015

View full text Add to dashboard Cite

The inflammatory hypothesis of schizophrenia (SZ) posits that inflammatory processes and neural-immune interactions are involved in its pathogenesis, and may underpin some of its neurobiological correlates. SZ is the psychiatric disorder causing the most severe burden of illness, not just owing to its psychiatric impairment, but also owing to its significant medical comorbidity. C-reactive protein (CRP) is a commonly used biomarker of systemic inflammation worldwide. There are some conflicting results regarding the behaviour of CRP in SZ. The aims of this study were to verify whether peripheral CRP levels are indeed increased in SZ, whether different classes of antipsychotics divergently modulate CRP levels and whether its levels are correlated with positive and negative symptomatology. With that in mind, we performed a meta-analysis of all cross-sectional studies of serum and plasma CRP levels in SZ compared to healthy subjects. In addition, we evaluated longitudinal studies on CRP levels before and after antipsychotic use. Our meta-analyses of CRP in SZ included a total of 26 cross-sectional or longitudinal studies comprising 85 000 participants. CRP levels were moderately increased in persons with SZ regardless of the use of antipsychotics and did not change between the first episode of psychosis and with progression of SZ (g=0.66, 95% confidence interval (95% CI) 0.43 to 0.88, P<0.001, 24 between-group comparisons, n=82 962). The extent of the increase in peripheral CRP levels paralleled the increase in severity of positive symptoms, but was unrelated to the severity of negative symptoms. CRP levels were also aligned with an increased body mass index. Conversely, higher age correlated with a smaller difference in CRP levels between persons with SZ and controls. Furthermore, CRP levels did not increase after initiation of antipsychotic medication notwithstanding whether these were typical or atypical antipsychotics (g=0.01, 95% CI -0.20 to 0.22, P=0.803, 8 within-group comparisons, n=713). In summary, our study provides further evidence of the inflammatory hypothesis of SZ. Whether there is a causal relationship between higher CRP levels and the development of SZ and aggravation of psychotic symptoms, or whether they are solely a marker of systemic low-grade inflammation in SZ, remains to be clarified.

show abstract

Section: Discussionmentioning

confidence: 97%

C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications

et al. 2015

View full text Add to dashboard Cite

show abstract

“…O conjunto desses achados levou à introdução de uma proposta de estadiamento do transtorno bipolar, parcialmente baseada em biomarcadores 17,58 . Assim, não são detectadas alterações no BDNF sérico nos estágios iniciais durante eutimia.…”

Section: Neuroplasticidadeunclassified

Marcadores periféricos e a fisiopatologia do transtorno bipolar

Magalhães¹,

Fries²,

Kapczinski³

2012

Rev. psiquiatr. clín.

Self Cite

View full text Add to dashboard Cite

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...

show abstract

“…Notably, mood stabilizers and antipsychotics have been shown to increase serum BDNF levels in BD patients (Machado-Vieira et al, 2009;Grande et al, 2012;Nishino et al, 2012). Kapczinski et al (2009a;2009b) proposed a staging model for BD. According to this model, each episode (both manic and depressive) is associated with changes in several markers, including a decrease in BDNF (Kapczinski et al, 2009b).…”

Section: Introductionmentioning

confidence: 99%

“…Kapczinski et al (2009a;2009b) proposed a staging model for BD. According to this model, each episode (both manic and depressive) is associated with changes in several markers, including a decrease in BDNF (Kapczinski et al, 2009b). The decreased BDNF levels reflect a decreased process of neurogenesis, which, in turn, may result in greater cognitive decline, both prognostic and functioning (Gama et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Effects of a single bout of maximal aerobic exercise on BDNF in bipolar disorder: A gender-based response

Schuch

Silveira

Zeni

et al. 2015

Psychiatry Research

View full text Add to dashboard Cite

The concept of staging in bipolar disorder: the role of BDNF and TNF-alpha as biomarkers

Cited by 31 publications

References 8 publications

C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications

C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications

Marcadores periféricos e a fisiopatologia do transtorno bipolar

Effects of a single bout of maximal aerobic exercise on BDNF in bipolar disorder: A gender-based response

Contact Info

Product

Resources

About