Meta-Analysis of Cytokine and Chemokine Genes in Schizophrenia

Hudson, Zachary; Miller, Brian J.

doi:10.3371/csrp.humi.070516

Cited by 36 publications

(10 citation statements)

References 16 publications

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“…There is strong evidence of immune-inflammatory changes in SZ patients with acute exacerbations or a first psychotic episode [15, 22, 38]. It has been suggested that IL-1β, IL-2, and IL-6 could be considered state markers, whereas TNF-α, IL-17, and IFN-γ might be considered trait markers [39].…”

Section: Discussionmentioning

confidence: 99%

The Relationship between Cytokines and Verbal Memory in Individuals with Schizophrenia and Their Unaffected Siblings

Rebouças

Rabelo‐da‐Ponte

Massuda

et al. 2018

Neuroimmunomodulation

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Background: Verbal memory impairment may be considered an endophenotype in schizophrenia (SZ), also affecting the siblings of SZ subjects. Furthermore, the immune-inflammatory system response has an important modulatory effect on brain processes, especially on memory circuits. Objective: Investigating the relationship between TNF-α and IL-6 and memory performance in patients with SZ, their unaffected siblings (SB) and healthy controls (HC). Methods: 35 subjects with SZ, 36 SB, and 47 HC underwent a neurocognitive assessment for verbal memory by means of the revised Hopkins Verbal Learning Test (HVLT-R) in addition to serum cytokines analyses. Results: SZ patients performed worse in HVLT-R than SB and HC, but SB and HC were not different. Regarding the biomarker levels, we found significant results of TNF-α for both groups. However, we did not find differences between groups after multiple-comparisons analysis. There were no significant correlations between episodic verbal memory, TNF-α, and IL-6. Conclusion: The results are compatible with the hypothesis that deficits in verbal memory of individuals with SZ could be secondary to inadequate functioning of cognitive processing areas, such as proactive cognitive control.

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Section: Discussionmentioning

confidence: 99%

The Relationship between Cytokines and Verbal Memory in Individuals with Schizophrenia and Their Unaffected Siblings

Rebouças

Rabelo‐da‐Ponte

Massuda

et al. 2018

Neuroimmunomodulation

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“…Despite the identification of these candidate biomarkers, other studies highlight that the current literature does not provide sufficient evidence that increased inflammation is a hallmark of all SCZ cases (Kroken et al, 2018). Some studies have identified markers that are related to antigen presentation and immune activity (Pouget et al, 2016), whereas others have revealed changes in inflammatory cytokines (Hudson and Miller, 2018;Kroken et al, 2018). These studies together indicate that some cases or stages of SCZ may involve the innate and/or adaptive immune system.…”

Section: Genetic Risk Factors That Interplay With Immunological Respomentioning

confidence: 99%

The Inflamed Brain in Schizophrenia: The Convergence of Genetic and Environmental Risk Factors That Lead to Uncontrolled Neuroinflammation

Comer

Carrier

Tremblay

et al. 2020

Front. Cell. Neurosci.

152

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“…The disease is related to genetic (Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014 ; Siegert et al, 2015 ; Richards et al, 2016 ) and environmental factors (Dean and Murray, 2005 ; Gallagher et al, 2016 ), and likely triggered through a complex interplay between the two (Davis et al, 2016 ; Mandelli et al, 2016 ). Epidemiological studies have implicated prenatal infection and immune genes variations, notably of complement component 4 linked to microglial refinement of neuronal circuits, in the development of schizophrenia (Müller et al, 2015 ; Estes and McAllister, 2016 ; Hudson and Miller, 2016 ; Sekar et al, 2016 ; Srinivas et al, 2016 ). Animal models of maternal immune activation (mIA) using the viral mimic Poly I:C, or other immune stimuli, display neurobehavioral impairments affecting motor control, anxiety, sociability, memory, and sensorimotor gating that are reminiscent of schizophrenia symptoms (Jones et al, 2011 ; Meyer, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Prenatal Immune Challenge in Mice Leads to Partly Sex-Dependent Behavioral, Microglial, and Molecular Abnormalities Associated with Schizophrenia

Hui

St-Pierre

Hajj

et al. 2018

Front. Mol. Neurosci.

124

129

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Epidemiological studies revealed that environmental factors comprising prenatal infection are strongly linked to risk for later development of neuropsychiatric disorders such as schizophrenia. Considering strong sex differences in schizophrenia and its increased prevalence in males, we designed a methodological approach to investigate possible sex differences in pathophysiological mechanisms. Prenatal immune challenge was modeled by systemic administration of the viral mimic polyinosinic-polycytidylic acid (Poly I:C) to C57BL/6 mice at embryonic day 9.5. The consequences on behavior, gene expression, and microglia—brain immune cells that are critical for normal development—were characterized in male vs. female offspring at adulthood. The cerebral cortex, hippocampus, and cerebellum, regions where structural and functional alterations were mainly described in schizophrenia patients, were selected for cellular and molecular analyses. Confocal and electron microscopy revealed most pronounced differences in microglial distribution, arborization, cellular stress, and synaptic interactions in the hippocampus of male vs. female offspring exposed to Poly I:C. Sex differences in microglia were also measured under both steady-state and Poly I:C conditions. These microglial alterations were accompanied by behavioral impairment, affecting for instance sensorimotor gating, in males. Consistent with these results, increased expression of genes related to inflammation was measured in cerebral cortex and hippocampus of males challenged with Poly I:C. Overall, these findings suggest that schizophrenia's higher incidence in males might be associated, among other mechanisms, with an increased microglial reactivity to prenatal immune challenges, hence determining disease outcomes into adulthood.

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Meta-Analysis of Cytokine and Chemokine Genes in Schizophrenia

Cited by 36 publications

References 16 publications

The Relationship between Cytokines and Verbal Memory in Individuals with Schizophrenia and Their Unaffected Siblings

The Relationship between Cytokines and Verbal Memory in Individuals with Schizophrenia and Their Unaffected Siblings

The Inflamed Brain in Schizophrenia: The Convergence of Genetic and Environmental Risk Factors That Lead to Uncontrolled Neuroinflammation

Prenatal Immune Challenge in Mice Leads to Partly Sex-Dependent Behavioral, Microglial, and Molecular Abnormalities Associated with Schizophrenia

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