Cytokines in Bipolar Disorder: <i>Recent Findings, Deleterious Effects But Promise for Future Therapeutics</i>

Brietzke, Elisa; Stabellini, Raquel; Grassi‐Oliveira, Rodrigo; Lafer, Beny

doi:10.1017/s1092852912000338

Cited by 49 publications

(30 citation statements)

References 159 publications

(204 reference statements)

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“…In contrast to acute neuroinflammatory conditions in MDD, however, astroglia and microglia do not proliferate (Najjar et al, 2013), consistent with a continuous, low grade inflammation. As for BPD, peripheral IL-2, IL-4 and IL-6 are found to be increased in manic episodes (Brietzke et al, 2011) whereas another meta-analysis revealed significant elevation of soluble interleukin (IL)-2 receptor (sIL-2R), TNF-a, soluble tumor necrosis factor receptor type 1 (sTNFR1) and soluble interleukin (IL)-6 receptor (sIL-6R) (Munkholm et al, 2013). In the case of schizophrenia, TNF-a, IFN-g, IL-12 and IL-2 are consistently elevated in chronic schizophrenic patients, while IL-1b, IL-6 and TGF-b correlate positively with disease activity (Miller et al, 2011).…”

Section: Purinergic Regulation Of Neuroinflammation In Cns Disordersmentioning

confidence: 92%

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

et al. 2016

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a b s t r a c tThe principle functions of neuroinflammation are to limit tissue damage and promote tissue repair in response to pathogens or injury. While neuroinflammation has utility, pathophysiological inflammatory responses, to some extent, underlie almost all neuropathology. Understanding the mechanisms that control the three stages of inflammation (initiation, propagation and resolution) is therefore of critical importance for developing treatments for diseases of the central nervous system. The purinergic signaling system, involving adenosine, ATP and other purines, plus a host of P1 and P2 receptor subtypes, controls inflammatory responses in complex ways. Activation of the inflammasome, leading to release of pro-inflammatory cytokines, activation and migration of microglia and altered astroglial function are key regulators of the neuroinflammatory response. Here, we review the role of P1 and P2 receptors in mediating these processes and examine their contribution to disorders of the nervous system. Firstly, we give an overview of the concept of neuroinflammation. We then discuss the contribution of P2X, P2Y and P1 receptors to the underlying processes, including a discussion of cross-talk between these different pathways. Finally, we give an overview of the current understanding of purinergic contributions to neuroinflammation in the context of specific disorders of the central nervous system, with special emphasis on neuropsychiatric disorders, characterized by chronic low grade inflammation or maternal inflammation. An understanding of the important purinergic contribution to neuroinflammation underlying neuropathology is likely to be a necessary step towards the development of effective interventions.

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Section: Purinergic Regulation Of Neuroinflammation In Cns Disordersmentioning

confidence: 92%

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

et al. 2016

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“…Elevated levels of cytokines are evident in the peripheral blood of schizophrenia and bipolar disorder patients, relative to healthy controls (Kunze et al 2013;Kim et al 2007). Specifically, increased levels of serum interleukin (IL)-1, IL-2, IL6 and tumour necrosis factor-alpha (TNF-a) have been found in schizophrenia (Potvin et al 2008;Theodoropoulou et al 2001), and elevated plasma cytokine levels of IL-2, IL-4, IL-6, IL-8 and TNF-a are also evident in bipolar disorder (Brietzke et al 2011;O'Brien et al 2006). Chronically elevated levels of cytokines can cause increased oxidative stress and alter neuronal function (Brietzke et al 2011;Schafers and Sorkin 2008), and may also contribute to the grey matter loss seen in schizophrenia and bipolar disorder (Viviani et al 2004).…”

Section: Pro-inflammatory Markers In Schizophrenia and Bipolar Disordermentioning

confidence: 99%

Stress, Schizophrenia and Bipolar Disorder

Green

Girshkin

Teroganova

et al. 2014

Behavioral Neurobiology of Stress-Related Disorders

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The role of stress in precipitating psychotic episodes in schizophrenia and bipolar disorder has long been acknowledged. However, the neurobiological mechanism/s of this association have remained elusive. Current neurodevelopmental models of psychosis implicate early dysfunction in biological systems regulating hypothalamic-pituitary-adrenal axis and immune function, with long-term effects on the development of the brain networks responsible for higher order cognitive processes and stress reactivity in later life. There is also increasing evidence of childhood trauma in psychosis, and its impact on the development of brain systems regulating stress. These findings are emerging in the context of a new era of epigenetic methods facilitating the study of environmental effects on gene expression. The evidence is thus converging: exposure to stress at critical periods in life may be an important factor in the development of the brain dysfunction that represents psychosis vulnerability, rather than merely interacting with an independent 'biological vulnerability' to manifest in psychosis.

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“…Cerebro-spinal fluid norepinephrine metabolite (3-methoxy-4-hydroxyphenylglycol (MHPG) is elevated in mania patients compared to the dopamine metabolite, homovanillic acid (HVA) or the serotonin metabolite, 5-hydroxyindoleacetic acid (HIAA) implying an excessive, abnormal noradrenergic activity in mania (Swan et al, 1983). Higher urinary catecholamine concentration in adulthood predicts higher levels of drug use (Brody et al, 2014). Levels of MHPG are decreased by lithium (Ostrow et al, 1984).…”

Section: Noradrenergic Mechanisms In Insulin Resistance Substance Usmentioning

confidence: 99%

Type 2 diabetes mellitus, drug addiction, bipolar disorder and epilepsy display overlapping aetiopathogenic mechanisms: Implication for prevention and pharmacotherapy

Oriaifo¹

2015

J. Med. Med. Sci

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The prevalence of diabetes and co-morbid diseases, especially in developing countries, may have already exceeded estimates. Accumulating reports indicate considerable underpinnings in the mechanisms of the aetiopathogenesis of metabolic syndrome, bipolar disorder, epilepsy and, recently, substance addiction. Continuing evidence incriminates dysfunction in genetic, mitochondrial and inflammatory cascade mechanisms as contributory factors to the dysregulation of neurotrophic, serotonergic, dopaminergic, adrenergic, glutamatergic, GABAergic and autophagic pathways. There may also be co-incident dysregulation of the global anti-oxidant network, the endogenous digitalis system, the vasopressin signalling and the hypothalamo-pituitary-adrenal axis. Nuclear factor-kappa B (NF-kappa B) signaling and reactive oxygen species lead to activation of the mammalian target of rapamycin complex I (mTORCI) and this process may be central to the aetiopathogenesis of drug addiction, obesity, foetal programming, diabetes mellitus, epilepsy and bipolar disorder. Antiglycaemics such as cannabinoid CB2 agonists, metformin, artesunate and valproate; insulin-mimetics such as glucagon-like peptide-I (GLP-I) and its analogues; phytomedicines from garlic and curcumin are now shown to exhibit neuroprotective effects. These agents which may down-regulate inflammatory cytokines, upregulate endothelial nitric oxide (eNOS) and peroxisome proliferator-activated receptor alpha (PPAR-α) signalling, attenuate mitochondrial dysfunction, enhance the actions of glucagon-like peptide-I (GLP-I), inhibit mTOR, NF-kappa B, interleukin-I β and glycogen synthase kinase-3 β stand to be of benefit in these illnesses which demonstrate considerable overlay in their aetopathogenic mechanisms. Underpinnings and bidirectional relationships between the metabolic syndrome and mental health disorders may pave way for common new fronts to drug development in translational cardiovascular psychiatry and neurology.

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Cytokines in Bipolar Disorder: Recent Findings, Deleterious Effects But Promise for Future Therapeutics

Cited by 49 publications

References 159 publications

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

Stress, Schizophrenia and Bipolar Disorder

Type 2 diabetes mellitus, drug addiction, bipolar disorder and epilepsy display overlapping aetiopathogenic mechanisms: Implication for prevention and pharmacotherapy

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