Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder

Brietzke, Elisa; Stertz, Laura; Fernandes, Brisa S.; Kauer-Sant’Anna, Márcia; Mascarenhas, Marcello Ávila; Vargas, Andréia Escosteguy; Chies, José Artur Bogo; Kapczinski, Flávio

doi:10.1016/j.jad.2008.12.001

Cited by 390 publications

(265 citation statements)

References 17 publications

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“…2 The presently observed aberrant CSF cytokine profile in euthymic patients with bipolar disorder (i.e., a selective activation of IL-1β concomitant with a reduction of IL-6) clearly differs from previous findings where cytokines of serum have been analyzed. [14][15][16] Although this discrepancy may relate to fluctuations of cytokines along with various states of the disease, the cytokine profile of the brain may also clearly differ from that of the periphery. 8,17,18 Supporting a central origin of the presently observed increased IL-1β concentration, a recent postmortem study demonstrated higher protein and mRNA levels of IL-1β in patients with bipolar disorder.…”

Section: Discussionmentioning

confidence: 99%

Elevation of cerebrospinal fluid interleukin-1β in bipolar disorder

Söderlund

Olsson

Samuelsson

et al. 2011

J Psychiatry Neurosci

168

121

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Background:In recent years, a role for the immune system in the pathogenesis of psychiatric diseases has gained increased attention.Although bipolar disorder appears to be associated with altered serum cytokine levels, a putative immunological contribution to its pathophysiology remains to be established. Hitherto, no direct analyses of cerebrospinal fluid (CSF) cytokines in patients with bipolar disorder have been performed. Methods: We analyzed CSF cytokine concentrations in euthymic patients with diagnosed bipolar dis order type I (n = 15) or type II (n = 15) and healthy volunteers (n = 30) using an immunoassay-based protein array multiplex system. Results: The mean interleukin (IL)-1β level (4.2 pg/mL, standard error of the mean [SEM] 0.5) was higher and the IL-6 level (1.5 pg/mL, SEM 0.2) was lower in euthymic bipolar patients than in healthy volunteers (0.8 pg/mL, SEM 0.04, and 2.6 pg/mL, SEM 0.2, respect ively). Patients with 1 or more manic/hypomanic episodes during the last year showed significantly higher levels of IL-1β (6.2 pg/mL, SEM 0.8; n = 9) than patients without a recent manic/hypomanic episode (3.1 pg/mL, SEM 1.0; n = 10). Limitations: All patients were in an euthymic state at the time of sampling. Owing to the large variety of drugs prescribed to patients in the present study, influence of medication on the cytokine profile cannot be ruled out. Conclusion: Our findings show an altered brain cytokine profile associated with the manifestation of recent manic/hypomanic episodes in patients with bipolar disorder. Although the causality remains to be established, these findings may suggest a pathophysiological role for IL-1β in bipolar disorder. In recent years, a role of the immune system in the pathogenesis of psychiatric diseases has gained increased attention. In this regard, many investigators have focused on cytokines, proteins that directly initiate and control immunological responses. We recently demonstrated a selective activation of brain interleukin (IL)-1β in schizophrenia, 2 a disease that appears similar to bipolar disorder with regard to symptomatology, treatment and risk genes. 3,4 Interestingly, a polymorphism in the promoter region of the IL1B gene has been suggested to comprise a shared genetic susceptibility for bipolar disorder and schizophrenia. 5 Indeed, bipolar disorder appears to be linked to inflammation, as indicated by genetic polymorphisms, gene expression and cytokine activation, 6 although direct evidence for a pathophysiological involvement of the immune system of the brain is still sparse. This may be 115 related to the fact that evaluation of cytokine levels in patients with bipolar disorder has been restricted to serum analyses. The bidirectional communication between the immune system of the brain and that of peripheral organs is complex, 7 and serum cytokines do not predict brain cytokine activation in healthy volunteers. 8 Hence, the immune system of the brain, including local cytokine release from microglia and astrocytes, may be independent of the immune sys...

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Section: Discussionmentioning

confidence: 99%

Elevation of cerebrospinal fluid interleukin-1β in bipolar disorder

Söderlund

Olsson

Samuelsson

et al. 2011

J Psychiatry Neurosci

168

121

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“…Os achados mais consistentes sugerem um aumento nos níveis de TNF-a e IL-6 nos episódios de mania e depressão, em comparação com eutímicos ou controles saudáveis [91][92][93][94] . Esses achados são especialmente evidentes quando pacientes com doença crônica são comparados com voluntários saudáveis 28,76,95 . Em pacientes eutímicos, observou-se que tanto o TNF-a quanto a IL-6 (outra citocina pró-inflamatória) encontravam--se elevados independentemente do estágio 56 .…”

Section: Mediadores Inflamatóriosunclassified

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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“…The biological mechanisms of BD still remain unclear, but it can be effectively conceptualized as a multi-systemic inflammatory disease [3]. To date, changes in peripheral inflammatory markers have been reported in BD such as cytokine profiles [4][5][6][7][8][9][10][11], acute phase proteins [12][13][14], and lymphocyte cell activation [5,[15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Neutrophil/lymphocyte and platelet/lymphocyte ratios in all mood states of bipolar disorder

Ayhan¹,

Çiçek²,

İnanlı³

et al. 2017

Psychiatry and Clinical Psychopharmacology

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Objectives: This study aims at researching the inflammatory cells and their ratios as inflammation markers in different phases of patients with bipolar disorder (BD). Methods: In this retrospective study, 79 manic, 61 depressed, 59 euthymic drug-naive patients with BD, and 86 control subjects have been evaluated for their complete blood count. Results: Neutrophil/lymphocyte ratio (NLR) was found to be significantly higher in manic, euthymic, and depressed patients with BD compared to control group. However, no difference was found between all patient and control groups regarding platelet/lymphocyte ratio (PLR). There was no difference among different phases of patient groups in terms of NLR and PLR. Conclusions: Our findings suggest that inflammatory process may have a role in all mood episodes of BD and NLR may be a useful trait inflammation marker for BD independent of mood episodes. However, further studies need to be conducted on the effect of inflammatory mechanisms on mood states of BD. ARTICLE HISTORY

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Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder

Cited by 390 publications

References 17 publications

Elevation of cerebrospinal fluid interleukin-1β in bipolar disorder

Elevation of cerebrospinal fluid interleukin-1β in bipolar disorder

Marcadores periféricos e a fisiopatologia do transtorno bipolar

Neutrophil/lymphocyte and platelet/lymphocyte ratios in all mood states of bipolar disorder

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