Serum zonulin and claudin-5 levels in patients with schizophrenia

Usta, Ayşe; Kılıç, Faruk; Demirdaş, Arif; Işık, Ümit; Doğuç, Duygu Kumbul; Bozkurt, Mehtap

doi:10.1007/s00406-020-01152-9

Cited by 37 publications

(27 citation statements)

References 39 publications

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“…Zonulin is a protein that increases small intestine permeability and contributes to innate intestinal immunity. Remarkably, increased serum zonulin levels have been observed in schizophrenia patients ( 162 , 163 ). Also, significant associations of gene polymorphisms of haptoglobulin (a product of zonulin processing) are found in schizophrenia ( 164 ).…”

Section: Changes In the Immune System Organs Associated With Schizoph...mentioning

confidence: 99%

Immune System Abnormalities in Schizophrenia: An Integrative View and Translational Perspectives

et al. 2022

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The immune system is generally known to be the primary defense mechanism against pathogens. Any pathological conditions are reflected in anomalies in the immune system parameters. Increasing evidence suggests the involvement of immune dysregulation and neuroinflammation in the pathogenesis of schizophrenia. In this systematic review, we summarized the available evidence of abnormalities in the immune system in schizophrenia. We analyzed impairments in all immune system components and assessed the level of bias in the available evidence. It has been shown that schizophrenia is associated with abnormalities in all immune system components: from innate to adaptive immunity and from humoral to cellular immunity. Abnormalities in the immune organs have also been observed in schizophrenia. Evidence of increased C-reactive protein, dysregulation of cytokines and chemokines, elevated levels of neutrophils and autoantibodies, and microbiota dysregulation in schizophrenia have the lowest risk of bias. Peripheral immune abnormalities contribute to neuroinflammation, which is associated with cognitive and neuroanatomical alterations and contributes to the pathogenesis of schizophrenia. However, signs of severe inflammation are observed in only about 1/3 of patients with schizophrenia. Immunological parameters may help identify subgroups of individuals with signs of inflammation who well respond to anti-inflammatory therapy. Our integrative approach also identified gaps in knowledge about immune abnormalities in schizophrenia, and new horizons for the research are proposed.

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Section: Changes In the Immune System Organs Associated With Schizoph...mentioning

confidence: 99%

Immune System Abnormalities in Schizophrenia: An Integrative View and Translational Perspectives

et al. 2022

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“…Moreover, specific mutations are associated with schizophrenia, including alterations in the 22q11.2 deletion syndrome (22qDS) -strongest monogenic risk allele for this disorder, and polymorphisms in claudin-5, a densely expressed tight junction molecule (Gur et al, 2017;Greene et al, 2018;Carrier et al, 2020) altogether revealing barrier dysfunction in schizophrenia patients (Greene et al, 2018;Crockett et al, 2021). Post-mortem brain sections from 22qDS patients and animal models of 22qDS both demonstrate reduced claudin-5 expression in the BBB, which in turn compromised BBB function (Nishiura et al, 2017;Guo et al, 2020;Crockett et al, 2021;Usta et al, 2021). Additionally, altered levels of vascular endothelial (VE)-cadherin and occludin in ECs were identified in schizophrenia.…”

Section: Altered Blood-brain Barrier and Angiogenesis In Schizophreniamentioning

confidence: 99%

From Neurodevelopmental to Neurodegenerative Disorders: The Vascular Continuum

Ouellette

Lacoste

2021

Front. Aging Neurosci.

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Structural and functional integrity of the cerebral vasculature ensures proper brain development and function, as well as healthy aging. The inability of the brain to store energy makes it exceptionally dependent on an adequate supply of oxygen and nutrients from the blood stream for matching colossal demands of neural and glial cells. Key vascular features including a dense vasculature, a tightly controlled environment, and the regulation of cerebral blood flow (CBF) all take part in brain health throughout life. As such, healthy brain development and aging are both ensured by the anatomical and functional interaction between the vascular and nervous systems that are established during brain development and maintained throughout the lifespan. During critical periods of brain development, vascular networks remodel until they can actively respond to increases in neural activity through neurovascular coupling, which makes the brain particularly vulnerable to neurovascular alterations. The brain vasculature has been strongly associated with the onset and/or progression of conditions associated with aging, and more recently with neurodevelopmental disorders. Our understanding of cerebrovascular contributions to neurological disorders is rapidly evolving, and increasing evidence shows that deficits in angiogenesis, CBF and the blood-brain barrier (BBB) are causally linked to cognitive impairment. Moreover, it is of utmost curiosity that although neurodevelopmental and neurodegenerative disorders express different clinical features at different stages of life, they share similar vascular abnormalities. In this review, we present an overview of vascular dysfunctions associated with neurodevelopmental (autism spectrum disorders, schizophrenia, Down Syndrome) and neurodegenerative (multiple sclerosis, Huntington’s, Parkinson’s, and Alzheimer’s diseases) disorders, with a focus on impairments in angiogenesis, CBF and the BBB. Finally, we discuss the impact of early vascular impairments on the expression of neurodegenerative diseases.

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“…Claudin-5 is a component of tight junctions and is specifically expressed in endothelial cells in the CNS. Polymorphism of claudin-5 has been associated with schizophrenia risk[ 65 ], and serum claudin-5 Levels were decreased in patients with schizophrenia[ 69 ]. The expression of claudin-5 in the hippocampus was reduced in patients with schizophrenia; the levels of claudin-5 correlated with the duration and age of onset of the disease[ 70 ].…”

Section: Blood Brain Barriermentioning

confidence: 99%

Novel approaches in schizophrenia-from risk factors and hypotheses to novel drug targets

Ľupták¹,

Michaličková²,

Fišar³

et al. 2021

WJP

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Schizophrenia is a severe psychiatric disorder characterized by emotional, behavioral and cognitive disturbances, and the treatment of schizophrenia is often complicated by noncompliance and pharmacoresistance. The search for the pathophysiological mechanisms underlying schizophrenia has resulted in the proposal of several hypotheses to explain the impacts of environmental, genetic, neurodevelopmental, immune and inflammatory factors on disease onset and progression. This review discusses the newest insights into the pathophysiology of and risk factors for schizophrenia and notes novel approaches in antipsychotic treatment and potential diagnostic and theranostic biomarkers. The current hypotheses focusing on neuromediators (dopamine, glutamate, and serotonin), neuroinflammation, the cannabinoid hypothesis, the gut-brain axis model, and oxidative stress are summarized. Key genetic features, including small nucleotide polymorphisms, copy number variations, microdeletions, mutations and epigenetic changes, are highlighted. Current pharmacotherapy of schizophrenia relies mostly on dopaminergic and serotonergic antagonists/partial agonists, but new findings in the pathophysiology of schizophrenia have allowed the expansion of novel approaches in pharmacotherapy and the establishment of more reliable biomarkers. Substances with promising results in preclinical and clinical studies include lumateperone, pimavanserin, xanomeline, roluperidone, agonists of trace amine-associated receptor 1, inhibitors of glycine transporters, AMPA allosteric modulators, mGLUR 2-3 agonists, D-amino acid oxidase inhibitors and cannabidiol. The use of anti-inflammatory agents as an add-on therapy is mentioned.

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Serum zonulin and claudin-5 levels in patients with schizophrenia

Cited by 37 publications

References 39 publications

Immune System Abnormalities in Schizophrenia: An Integrative View and Translational Perspectives

Immune System Abnormalities in Schizophrenia: An Integrative View and Translational Perspectives

From Neurodevelopmental to Neurodegenerative Disorders: The Vascular Continuum

Novel approaches in schizophrenia-from risk factors and hypotheses to novel drug targets

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