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    • "The MHC region contains many immune-related genes including those involved in antigen presentation and inflammatory mediators. These findings are consistent with two previous GWAS also implicating this region in schizophrenia (Shi et al. 2009; Stefansson et al. 2009). "
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    ABSTRACT: Schizophrenia is characterised by hallucinations, delusions, depression-like so-called negative symptoms, cognitive dysfunction, impaired neurodevelopment and neurodegeneration. Epidemiological and genetic studies strongly indicate a role of inflammation and immunity in the pathogenesis of symptoms of schizophrenia. Evidence accrued over the last two decades has demonstrated that there are a number of pathways through which systemic inflammation can exert profound influence on the brain leading to changes in mood, cognition and behaviour. The peripheral immune system-to-brain communication pathways have been studied extensively in the context of depression where inflammatory cytokines are thought to play a key role. In this review, we highlight novel evidence suggesting an important role of peripheral immune-to-brain communication pathways in schizophrenia. We discuss recent population-based longitudinal studies that report an association between elevated levels of circulating inflammatory cytokines and subsequent risk of psychosis. We discuss emerging evidence indicating potentially important role of blood-brain barrier endothelial cells in peripheral immune-to-brain communication, which may be also relevant for schizophrenia. Drawing on clinical and preclinical studies, we discuss whether immune-mediated mechanisms could help to explain some of the clinical and pathophysiological features of schizophrenia. We discuss implication of these findings for approaches to diagnosis, treatment and research in future. Finally, pointing towards links with early-life adversity, we consider whether persistent low-grade activation of the innate immune response, as a result of impaired foetal or childhood development, could be a common mechanism underlying the high comorbidity between certain neuropsychiatric and physical illnesses, such as schizophrenia, depression, heart disease and type-two diabetes.
    Psychopharmacology 06/2015; DOI:10.1007/s00213-015-3975-1 · 3.88 Impact Factor
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    • "However, a growing body of evidence suggests that schizophrenia and certain autoimmune diseases may share some key clinical, epidemiological and genetic features [1]. Early genetic studies reported an association between schizophrenia and chromosome 6p22–24, which includes the human major histocompatibility complex (MHC) region [17], while recent genome-wide association studies (GWASs) have identified several genes within the extended MHC region as a susceptibility locus for schizophrenia in individuals from European [15] [18] [22], Japanese [6] and Chinese [29] [34] populations . These different lines of evidence suggest that, potentially, immune abnormalities play some unknown role in the etiology of schizophrenia [25], increasing the susceptibility for schizophrenia in individuals with genetically altered immune functions [13]. "
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    ABSTRACT: Epidemiological studies have indicated that both maternal bacterial and viral infections during pregnancy increase the risk of schizophrenia among offspring, but to date there is not clear explanation for this increased risk. Previously, the decreased C4b-binding protein (C4BP), a potent circulating soluble inhibitor of the classical and lectin pathways of complement, was reported to be associated with risk of schizophrenia. Here, we analyzed 4 common single nucleotide polymorphisms (SNPs) of C4BPB and 5 SNPs of C4BPA in a group of 556 schizophrenia patients and a matched group of 610 healthy controls to see if the genes C4BPB and C4BPA, which encode C4BP, may confer a susceptibility to schizophrenia. Comparing the genotype and allele frequencies of those SNPs between cases and controls, we found no association between the C4BPB/C4BPA variants and schizophrenia. Our results provided preliminary evidence that C4BPB/C4BPA may not confer susceptibility to schizophrenia among Han Chinese. Further genetic studies from large-scale population are required to obtain more conclusive results. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Neuroscience Letters 02/2015; 590. DOI:10.1016/j.neulet.2015.02.005 · 2.03 Impact Factor
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    • "Delta-9-tetrahydrocannabinol (D 9 THC), the main 72 psychoactive substance in Cannabis sativa, acts as an exogenous 73 (GABA) terminations (Devane et al., 1992; Chevaleyre et al., 2006), 82 but they are also present in the periphery of the nervous system 83 (Pertwee, 1999). CB2-Rs have a similar structure and are predom- 84 inantly expressed in the spleen and immune cells (Graham et al., 85 2009). Although the proportion of CB2-Rs in the CNS is lower than 86 that of CB1-Rs, their presence in brain cells has been demonstrated 87 (Onaivi et al., 2012). "
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    ABSTRACT: Background Endocannabinoid system is involved in the regulation of the brain-immune axis. Cannabis consumption is related with the development, course, and severity of psychosis. The epidemiological evidence for increased occurrence of immunological alterations in patients with psychosis has not been sufficiently addressed. The aim of this review is to establish whether there is any scientific evidence of the influence of cannabinoids on aspects of immunity that affect susceptibility to psychotic disorder induction. Methods A comprehensive search of PubMed /MEDLINE, EMBASE and ISI Web of Knowledge was performed using combinations of key terms distributed into three blocks: “immune”, “cannabinoid”, and “endocannabinoid receptor”. Studies were considered to be eligible for the review if they were original articles, they reported a quantitative or qualitative relation between cannabinoid ligands, their receptors, and immune system, and they were carried out in vitro or in mammals, included humans. All the information was systematically extracted and evaluated. Results We identified 122 articles from 446 references. Overall, endocannabinoids enhanced immune response, whereas exogenous cannabinoids had immunosuppressant effects. A general change in the immune response from Th1 to Th2 was also demonstrated for cannabinoid action. Endogenous and synthetic cannabinoids also modulated microglia function and neurotransmitter secretion. Conclusion The actions of cannabinoids through the immune system are quite regular and predictable in the peripheral but remain fuzzy in the central nervous system. Despite this uncertainty, it may be hypothesized that exposure to exocannabinoids, in particular during adolescence might prompt immunological dysfunctions that potentially cause a latent vulnerability to psychosis. Further investigations are warranted to clarify the relationship between the immunological effects of cannabis and psychosis.
    Brain Behavior and Immunity 08/2014; 40. DOI:10.1016/j.bbi.2014.01.018 · 5.89 Impact Factor
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