Revisiting inflammation in bipolar disorder

Fries, Gabriel R.; Walss‐Bass, Consuelo; Bauer, Moisés Evandro; Teixeira, Antônio Lúcio

doi:10.1016/j.pbb.2018.12.006

Cited by 121 publications

(86 citation statements)

References 133 publications

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“…Several different mechanisms have been proposed to explain the role of immune dysfunction in BD, 171 including changes in blood-brain barrier, cell death-induced release of damage-associate molecular patterns with consequent immune activation, genetic mechanisms, dysfunction of the gut-brain axis, and a role of the kynurenine pathway. Activation of the kynurenine pathway by cytokines such as interferon-gamma (IFN-γ) and TNF-α is described as one of several contributors to psychiatric pathogeneses.…”

Section: Immune-inflammatory Imbalance and Kynurenine Pathwaymentioning

confidence: 99%

Neurobiology of bipolar disorders: a review of genetic components, signaling pathways, biochemical changes, and neuroimaging findings

Scaini

Valvassori

Diaz

et al. 2020

Braz. J. Psychiatry

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Bipolar disorder (BD) is a chronic mental illness characterized by changes in mood that alternate between mania and hypomania or between depression and mixed states, often associated with functional impairment. Although effective pharmacological and non-pharmacological treatments are available, several patients with BD remain symptomatic. The advance in the understanding of the neurobiology underlying BD could help in the identification of new therapeutic targets as well as biomarkers for early detection, prognosis, and response to treatment in BD. In this review, we discuss genetic, epigenetic, molecular, physiological and neuroimaging findings associated with the neurobiology of BD. Despite the advances in the pathophysiological knowledge of BD, the diagnosis and management of the disease are still essentially clinical. Given the complexity of the brain and the close relationship between environmental exposure and brain function, initiatives that incorporate genetic, epigenetic, molecular, physiological, clinical, environmental data, and brain imaging are necessary to produce information that can be translated into prevention and better outcomes for patients with BD.

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Section: Immune-inflammatory Imbalance and Kynurenine Pathwaymentioning

confidence: 99%

Neurobiology of bipolar disorders: a review of genetic components, signaling pathways, biochemical changes, and neuroimaging findings

Scaini

Valvassori

Diaz

et al. 2020

Braz. J. Psychiatry

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“…In mood disorders, for example, there already exists evidence for correlations between both the kynurenine metabolic pathway and inflammation. One example is bipolar disorder, where microglia are shown to be overactive and levels of KYNA were elevated in the CSF [32][33][34]. Another example is depression, where patients showed decreased levels of KYNA, QUIN, and kynurenine, correlating with pro-inflammatory cytokines [35][36][37].…”

Section: Introductionmentioning

confidence: 99%

Effects of inflammation on the kynurenine pathway in schizophrenia — a systematic review

Pedraz-Petrozzi

Elyamany

Rummel

et al. 2020

J Neuroinflammation

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Background: In the last decade, there has been growing evidence that an interaction exists between inflammation and the kynurenine pathway in schizophrenia. Additionally, many authors found microglial activation in cases of schizophrenia due to inflammatory mechanisms related mostly to an increase of pro-inflammatory cytokines. In order to gain new insights into the pathophysiology of schizophrenia, it is important to incorporate the latest published evidence concerning inflammatory mechanisms and kynurenine metabolism. This systematic review aims to collect reliable recent findings within the last decade supporting such a theory. Methods: A structured search of electronic databases was conducted for publications between 2008 and 2018 to identify eligible studies investigating patients with schizophrenia/psychosis and the relationship between inflammation and kynurenine pathway. Applicable studies were systematically scored using the NIH Quality Assessment Tools. Two researchers independently extracted data on diagnosis (psychosis/schizophrenia), inflammation, and kynurenine/tryptophan metabolites. Results: Ten eligible articles were identified where seven studies assessed blood samples and three assessed cerebrospinal fluid in schizophrenic patients. Of these articles: Four investigated the relationship between immunoglobulins and the kynurenine pathway and found correlations between IgA-mediated responses and levels of tryptophan metabolites (i.e., kynurenine pathway). Five examined the correlation between cytokines and kynurenine metabolites where three showed a relationship between elevated IL-6, TNF-α concentrations, and the kynurenine pathway. Only one study discovered correlations between IL-8 and the kynurenine pathway. Two studies showed correlations with lower concentrations of IL-4 and the kynurenine pathway. Moreover, this systematic review did not find a significant correlation between CRP (n = 1 study), IFN-γ (n = 3 studies), and the kynurenine pathway in schizophrenia.

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“…BD is a manic-depressive disorder that causes sudden changes in mood, concentration, energy, and activity levels, ranging from manic to depressive episodes. Several studies have associated BD within single-nucleotide polymorphisms (SNPs) in genes encoding cytokines or immune function (IFNg, IL-6, IL-1, TLR2, TLR4, PTGS2, CCL2, and CCL3) (Fries et al, 2019). A transcriptome-wide analysis included 1600 patients with SCZ and BD and reported the upregulation of members of IFN and NF-kB pathways (Guan et al, 2019).…”

Section: Causal Factors Of Immune Dysregulation In Mental Disordersmentioning

confidence: 99%

Neuroimmune Mechanisms and Sex/Gender-Dependent Effects in the Pathophysiology of Mental Disorders

Kokkosis¹,

Tsirka²

2020

The Journal of Pharmacology and Experimental Therapeutics

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Innate and adaptive immune mechanisms have emerged as critical regulators of CNS homeostasis and mental health. A plethora of immunologic factors have been reported to interact with emotion-and behavior-related neuronal circuits, modulating susceptibility and resilience to mental disorders. However, it remains unclear whether immune dysregulation is a cardinal causal factor or an outcome of the pathologies associated with mental disorders. Emerging variations in immune regulatory pathways based on sex differences provide an additional framework for discussion in these psychiatric disorders. In this review, we present the current literature pertaining to the effects that disrupted immune pathways have in mental disorder pathophysiology, including immune dysregulation in CNS and periphery, microglial activation, and disturbances of the blood-brain barrier. In addition, we present the suggested origins of such immune dysregulation and discuss the gender and sex influence of the neuroimmune substrates that contribute to mental disorders. The findings challenge the conventional view of these disorders and open the window to a diverse spectrum of innovative therapeutic targets that focus on the immune-specific pathophenotypes in neuronal circuits and behavior. SIGNIFICANCE STATEMENT The involvement of gender-dependent inflammatory mechanisms on the development of mental pathologies is gaining momentum. This review addresses these novel factors and presents the accumulating evidence introducing microglia and proinflammatory elements as critical components and potential targets for the treatment of mental disorders.

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Revisiting inflammation in bipolar disorder

Cited by 121 publications

References 133 publications

Neurobiology of bipolar disorders: a review of genetic components, signaling pathways, biochemical changes, and neuroimaging findings

Neurobiology of bipolar disorders: a review of genetic components, signaling pathways, biochemical changes, and neuroimaging findings

Effects of inflammation on the kynurenine pathway in schizophrenia — a systematic review

Neuroimmune Mechanisms and Sex/Gender-Dependent Effects in the Pathophysiology of Mental Disorders

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