Cytokines and C-reactive protein alterations with respect to cognitive impairment in schizophrenia and bipolar disorder: A systematic review

Misiak, Błażej; Stańczykiewicz, Bartłomiej; Kotowicz, Kamila; Rybakowski, Janusz; Samochowiec, Jerzy; Frydecka, Dorota

doi:10.1016/j.schres.2017.04.015

Cited by 159 publications

(113 citation statements)

References 109 publications

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“…Notably, accumulated evidence suggests that increased inflammation can have detrimental effects on cognitive function . In humans, for example, elevated levels of inflammatory markers have been shown to be associated with lower cognitive function in various diseases and conditions where cognitive dysfunction plays a role, such as depression, schizophrenia, cocaine addiction, cerebrovascular disease, and cognitive decline . In line with this, we demonstrated that elevated serum IL‐6 levels in PTSD patients were associated with worse cognitive function, suggesting that their cognitive dysfunction may be due at least partly to increased inflammation (Fig.…”

Section: Mechanisms Underlying the Link Between Inflammation And Ptsdsupporting

confidence: 82%

Inflammation and post‐traumatic stress disorder

Hori

Kim

2019

Psychiatry Clin Neurosci

261

176

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While post‐traumatic stress disorder (PTSD) is currently diagnosed based solely on classic psychological and behavioral symptoms, a growing body of evidence has highlighted a link between this disorder and alterations in the immune and inflammatory systems. Epidemiological studies have demonstrated that PTSD is associated with significantly increased rates of physical comorbidities in which immune dysregulation is involved, such as metabolic syndrome, atherosclerotic cardiovascular disease, and autoimmune diseases. In line with this, a number of blood biomarker studies have reported that compared to healthy controls, individuals with PTSD exhibit significantly elevated levels of proinflammatory markers, such as interleukin‐1β, interleukin‐6, tumor necrosis factor‐α, and C‐reactive protein. Moreover, various lines of animal and human research have suggested that inflammation is not only associated with PTSD but also can play an important role in its pathogenesis and pathophysiology. In this review, we first summarize evidence suggestive of increased inflammation in PTSD. We then examine findings that suggest possible mechanisms of inflammation in this disorder in terms of two different but interrelated perspectives: putative causes of increased proinflammatory activities and potential consequences that inflammation generates. Given that there is currently a dearth of treatment options for PTSD, possibilities of new therapeutic approaches using pharmacological and non‐pharmacological treatments/interventions that have anti‐inflammatory effects are also discussed. Despite the increasing attention given to the inflammatory pathology of PTSD, there remains much to be elucidated, including more detailed mechanisms of inflammation, potential usefulness of inflammatory biomarkers as diagnostic and prognostic markers, and efficacy of novel treatment strategies targeting inflammation.

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Section: Mechanisms Underlying the Link Between Inflammation And Ptsdsupporting

confidence: 82%

Inflammation and post‐traumatic stress disorder

Hori

Kim

2019

Psychiatry Clin Neurosci

261

176

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“…However, a recent systematic review (Misiak et al, 2017a) has found raised inflammatory markers to be associated with cognitive impairment in schizophrenia, which may add confidence in our own findings.…”

Section: Strengths and Limitationssupporting

confidence: 72%

Associated illness severity in schizophrenia and diabetes mellitus: A systematic review

Perry

Salimkumar

Green

et al. 2017

Psychiatry Research

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(2017) Associated illness severity in schizophrenia and diabetes mellitus : a systematic review. Psychiatry research. Permanent WRAP URL:http://wrap.warwick.ac.uk/89163 Copyright and reuse:The Warwick Research Archive Portal (WRAP) makes this work by researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available.Copies of full items can be used for personal research or study, educational, or not-for-profit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. ResultsEleven observational studies were included in the analysis. Ten presented evidence in support of an association between schizophrenia severity and dysglycaemia. This association appeared particularly strong regarding negative symptomatology and impaired cognitive function, between which there may be some overlap. Studies examining positive symptomatology returned mixed results. ConclusionWhilst study design varied amongst the included studies, the results suggest that further work examining the effect of hyperglycaemia on schizophrenia severity may be relevant, particularly longitudinal studies assessing negative symptomatology and cognitive function. To the authors' knowledge, this is the first systematic review conducted to address this question.

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“…Interestingly, a recent systematic review assessing cytokines and cognitive impairment in subjects with SZ and bipolar disorder (BD) claimed that most studies reported positive findings for TNF-α and cognitive performance, but that some did not find correlations between these 2 factors [25]. Seven studies tested the effects of IL-6 by means of neuropsychological tests on individuals with SZ or BD, but only 3 found a negative correlation between IL-6 and cognitive performance.…”

Section: Discussionmentioning

confidence: 99%

“…A meta-analysis found that patients with first-episode psychosis and relapsed patients show higher levels of proinflammatory cytokines than unaffected individuals [22]. Moreover, there is considerable evidence of cytokines changes in SZ, but also imbalances involving broader areas of the immune-inflammatory system, such as the glial cells, autoantibodies, C-reactive protein (CRP), and kynurenine [23-25]. Similar changes have been observed in the siblings of patients with SZ, demonstrating that both affected and unaffected siblings have elevated concentrations of proteins associated with an inflammatory response [26].…”

Section: Introductionmentioning

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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Cytokines and C-reactive protein alterations with respect to cognitive impairment in schizophrenia and bipolar disorder: A systematic review

Cited by 159 publications

References 109 publications

Inflammation and post‐traumatic stress disorder

Inflammation and post‐traumatic stress disorder

Associated illness severity in schizophrenia and diabetes mellitus: A systematic review

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

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