Postmortem evidence of brain inflammatory markers in bipolar disorder: a systematic review

Giridharan, Vijayasree V.; Sayana, Pavani; Pinjari, Omar F.; Ahmad, Naveed; Rosa, Maria Inês da; Quevedo, Joao L De; Barichello, Tatiana

doi:10.1038/s41380-019-0448-7

Cited by 88 publications

(50 citation statements)

References 119 publications

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“…[165][166][167][168][169] However, another systematic review claims that an absolute conclusion cannot be reached regarding the presence of neuroinflammation in BD, since the findings are not consistent. 170 Several different mechanisms have been proposed to explain the role of immune dysfunction in BD, 171 including changes in blood-brain barrier, cell deathinduced 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-g) and TNF-a 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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“…Images were obtained on a General Electric Signa HDxt 1.5-Tesla scanner at Toronto General Hospital in Toronto, Ontario, Canada. The scanning parameters for the 3D T1-weighted fast spoiled gradient echo sequence were as follows: slice thickness = 1 mm, repetition time = 10.74 ms, echo time = 4.20 msec, inversion time = 450 msec, matrix size = 256 mm × 256 mm, field of view = 220 mm, flip angle = 15 • , voxel size = 0.86 × 0.85 × 1 mm 3 , and scan duration = 15 min 3 s. There was a total of 146 slices produced in the axial plane.…”

Section: Neuroimagingmentioning

confidence: 99%

“…Multiple meta-analyses have documented alterations in peripheral markers of inflammation, such as acute phase proteins (e.g., C-reactive protein [CRP]) and inflammatory cytokines (e.g., tumor necrosis factor-α [TNF-α], interleukin-6 [IL6]) [1,2]. Direct evidence of neuroinflammation has been scarcer, but has supported the hypothesis of inflammatory dysregulation [3][4][5]. In addition, inflammatory mediators have been consistently associated with neurostructural abnormalities in individuals with BD [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicle Biomarkers Reveal Inhibition of Neuroinflammation by Infliximab in Association with Antidepressant Response in Adults with Bipolar Depression

Mansur

Delgado-Peraza

Subramaniapillai

et al. 2020

Cells

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Accumulating evidence suggests that neuroinflammation is involved in bipolar disorder (BD) pathogenesis. The tumor necrosis factor-alpha (TNF-α) antagonist infliximab was recently reported to improve depressive symptoms in a subpopulation of individuals with BD and history of childhood maltreatment. To explore the mechanistic mediators of infliximab’s effects, we investigated its engagement with biomarkers of cellular response to inflammation derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We hypothesized that infliximab, compared to placebo, would decrease TNF-α receptors (TNFRs) and nuclear factor-kappa B (NF-κB) pathway signaling biomarkers, and that history of childhood abuse would moderate infliximab’s effects. We immunocaptured NEVs from plasma samples collected at baseline and at weeks 2, 6, and 12 (endpoint) from 55 participants of this clinical trial and measured NEV biomarkers using immunoassays. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging at baseline and endpoint. Childhood physical abuse moderated treatment by time interactions for TNFR1 (χ2 = 9.275, p = 0.026), NF-κB (χ2 = 13.825, p = 0.003), and inhibitor of NF-κB (IκBα)α (χ2 = 7.990, p = 0.046), indicating that higher levels of physical abuse were associated with larger biomarker decreases over time. Moreover, the antidepressant response to infliximab was moderated by TNFR1 (χ2 = 7.997, p = 0.046). In infliximab-treated participants, reductions in TNFR1 levels were associated with improvement of depressive symptoms, an effect not detected in the placebo group. Conversely, reductions in TNFR1 levels were associated with increased global cortical thickness in infliximab- (r = −0.581, p = 0.029), but not placebo-treated, patients (r = 0.196, p = 0.501). In conclusion, we report that NEVs revealed that infliximab engaged the TNFR/NF-κB neuro-inflammatory pathway in individuals with BD, in a childhood trauma-dependent manner, which was associated with clinical response and brain structural changes.

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“…Notably, the emergence of immunoneuropsychiatry witnesses the essential role of immune processes in maintaining CNS homeostasis and resilience 29 . Previous studies have suggested a chronic, persistent, and low‐level inflammation underlying the pathogenesis of mood disorders 29,30 . Of note, the gut ecosystem could be a major reservoir for this inflammatory process 31 .…”

Section: The Mgb Axismentioning

confidence: 99%

Gut microbial clues to bipolar disorder: State‐of‐the‐art review of current findings and future directions

Lai

Jiang

Zhang

et al. 2020

Clinical & Translational Med

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Trillions of microorganisms inhabiting in the human gut play an essential role in maintaining physical and mental health. The connections between gut microbiome and neuropsychiatric diseases have been recently identified. The pathogenesis of bipolar disorder, a spectrum of diseases manifesting with mood and energy fluctuations, also seems to be involved in the bidirectional modulation of the microbiome‐gut‐brain (MGB) axis. In this review, we briefly introduce the concept of MGB axis, and then focus on the previous findings in human studies associated with bipolar disorder. These studies provided preliminary evidences on the gut microbial alterations in bipolar disorder. Limitations in these studies and future directions in this research field, such as fecal microbiome transplantation and microbiome‐targeted therapy, were discussed. A research framework linking gut microbiome to determinants and health‐related outcomes in BD was also proposed. Better characterizing and understanding of gut microbial biosignatures in bipolar patients contribute to clarify the etiology of this intractable disease and pave the new way for treatment innovation.

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Postmortem evidence of brain inflammatory markers in bipolar disorder: a systematic review

Cited by 88 publications

References 119 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

Extracellular Vesicle Biomarkers Reveal Inhibition of Neuroinflammation by Infliximab in Association with Antidepressant Response in Adults with Bipolar Depression

Gut microbial clues to bipolar disorder: State‐of‐the‐art review of current findings and future directions

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