Altered structural connectivity and cytokine levels in Schizophrenia and Genetic high-risk individuals: Associations with disease states and vulnerability

Wang, Yan; Wei, Yange; Edmiston, E. Kale; Womer, Fay Y.; Zhang, Xizhe; Duan, Jia; Zhu, Yue; Zhang, Ran; Zhang, Yin; Zhang, Yifan; Jiang, Xiaowei; Wei, Shengnan; Liu, Zhuang; Zhang, Yanbo; Tang, Yanqing; Wang, Fei

doi:10.1016/j.schres.2020.05.044

Cited by 21 publications

(13 citation statements)

References 68 publications

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“…Indeed, reduced white matter integrity (including FA of the IFOF) of both MDD [93] and BD [117] participants has been previously associated with increased serum pro-inflammatory cytokine concentrations. Negative correlations between FA and circulating inflammatory mediators have also been reported in schizophrenia [118], Alzheimer's disease [119], and healthy adults [120,121]. In this regard, the absence of a significant correlation between CRP and FA in the current study was unexpected.…”

Section: Discussionsupporting

confidence: 44%

Replicable association between human cytomegalovirus infection and reduced white matter fractional anisotropy in major depressive disorder

Zheng

Bergamino

Ford

et al. 2021

Neuropsychopharmacol.

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Major depressive disorder (MDD) is associated with reductions in white matter microstructural integrity as measured by fractional anisotropy (FA), an index derived from diffusion tensor imaging (DTI). The neurotropic herpesvirus, human cytomegalovirus (HCMV), is a major cause of white matter pathology in immunosuppressed populations but its relationship with FA has never been tested in MDD despite the presence of inflammation and weakened antiviral immunity in a subset of depressed patients. We tested the relationship between FA and HCMV infection in two independent samples consisting of 176 individuals with MDD and 44 healthy controls (HC) (Discovery sample) and 88 participants with MDD and 48 HCs (Replication sample). Equal numbers of HCMV positive (HCMV+) and HCMV negative (HCMV−) groups within each sample were balanced on ten different clinical/demographic variables using propensity score matching. Anti-HCMV IgG antibodies were measured using a solid-phase ELISA. In the Discovery sample, significantly lower FA was observed in the right inferior fronto-occipital fasciculus (IFOF) in HCMV+ participants with MDD compared to HCMV− participants with MDD (cluster size 1316 mm3; pFWE < 0.05, d = −0.58). This association was confirmed in the replication sample by extracting the mean FA from this exact cluster and applying the identical statistical model (p < 0.05, d = −0.45). There was no significant effect of diagnosis or interaction between diagnosis and HCMV in either sample. The effect of chronic HCMV infection on white matter integrity may—in at-risk individuals—contribute to the psychopathology of depression. These findings may provide a novel target of intervention for a subgroup of patients with MDD.

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Section: Discussionsupporting

confidence: 44%

Replicable association between human cytomegalovirus infection and reduced white matter fractional anisotropy in major depressive disorder

Zheng

Bergamino

Ford

et al. 2021

Neuropsychopharmacol.

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“…It is well-known that cytokines are key messengers in the cross-talk between the central nervous system (CNS) and immune cells. In the light of this, several studies have hypothesized that in patients with schizophrenia and severe mood disorders, the proinflammatory cytokine microenvironment is likely involved in the pathogenesis and pathophysiology of schizophrenia and the ensuing psychopathological symptoms (10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Cytokine Imbalance in Schizophrenia. From Research to Clinic: Potential Implications for Treatment

2021

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Cytokines are one of the most important components of the immune system. They orchestrate the brain's response to infectious and other exogenous insults and are crucial mediators of the cross-talk between the nervous and immune systems. Epidemiological studies have demonstrated that severe infections and autoimmune disorders, in addition to genetic predisposition, are risk factors for schizophrenia. Furthermore, maternal infection during pregnancy appears to increase the risk of schizophrenia, and proinflammatory cytokines may be negatively involved in the neurodevelopmental process. A cytokine imbalance has been described in the blood and cerebrospinal fluid of schizophrenia patients, particularly in the T helper type 1 [Th1] and type 2 [Th2] cytokines, albeit the results of such studies appear to be contradictory. Chronic stress, likewise, appears to contribute to a lasting proinflammatory state and likely also promotes the disorder. The aim of this mini-review is to investigate the roles of different cytokines in the pathophysiology of schizophrenia and define how cytokines may represent key molecular targets to regulate for the prevention and treatment of schizophrenia. How current antipsychotic drugs impact cytokine networks is also evaluated. In this context, we propose to change the focus of schizophrenia from a traditionally defined brain disorder, to one that is substantially impacted by the periphery and immune system.

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“…Cytokines can be necessary in the pathophysiology of SZ. Meta-analyses of cross-sectional studies have shown that antipsychotic naiveα [17].…”

Section: Prevalence and Epidemiologymentioning

confidence: 99%

“…White matter abnormalities which are related to disable brain places is a big part in his illness. Neuroprogressive symptoms is a big element in schizophrenia, such as structural brain changes [17].…”

Section: Pathobiology and Etiologymentioning

confidence: 99%

“…Increasing evidence suggests that individuals at genetic high risk for SZ (GHR-SZ) often share brain structural and immunological abnormalities with patients with SZ .IL-6, a pro-inflammatory cytokine, has a big responsible for the acute phase response in SZ, which leads to the physiologic and biochemical changes during disease states. The role of leptin has been recently considered an adipocyte-derived hormone/cytokine in the nervous system of patients with schizophrenia [17].…”

Section: Cellular and Molecular Biology Of Schizophreniamentioning

confidence: 99%

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Schizophrenia: Current and Perspectives

Ahadi

2021

BJSTR

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Schizophrenia is one of the most prevalent nervous system related disorders with a severe and progressive symptom. Main target population of this disease is the people after 60 years old. Several etiological factors are involved in Schizophrenia pathogenesis including trauma, stroke, central nervous system viral infection, genetic and epigenetics elements. We focus here on molecular biology aspect of schizophrenia manifestation. New findings about pathogenesis of this disease and pathways deal with schizophrenia will present in this review and finally we propose here some probable strategies applicable for treatment of this disorder. Molecular and cellular studies of schizophrenia will provide new strategies for management of this complex disorder.

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Altered structural connectivity and cytokine levels in Schizophrenia and Genetic high-risk individuals: Associations with disease states and vulnerability

Cited by 21 publications

References 68 publications

Replicable association between human cytomegalovirus infection and reduced white matter fractional anisotropy in major depressive disorder

Replicable association between human cytomegalovirus infection and reduced white matter fractional anisotropy in major depressive disorder

Cytokine Imbalance in Schizophrenia. From Research to Clinic: Potential Implications for Treatment

Schizophrenia: Current and Perspectives

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