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      The Interplay of Inflammatory Processes and Cognition in Alcohol Use Disorders—A Systematic Review

      systematic-review

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          Abstract

          Rationale: Of late, evidence emerges that the pathophysiology of psychiatric diseases and their affiliated symptomatologies are at least partly contributable to inflammatory processes. Also in alcohol use disorders (AUD), this interaction is strongly apparent, with severely immunogenic liver cirrhosis being one of the most critical sequelae of chronic abusive drinking. This somatic immune system activation negatively impacts brain functioning, and additionally, alcohol abuse appears to have a direct detrimental effect on the brain by actively stimulating its immune cells and responses. As cognitive decline majorly contributes to AUD’s debility, it is important to know to what extent impairment of cognitive functioning is due to these (neuro-)inflammatory aberrations.

          Method: We hereby summarize the current existing literature on the interplay between AUD, inflammation, and cognition in a systematic review according to the PRISMA-P guidelines for the systematic review.

          Main findings: Although literature on the role of inflammation in alcohol use-related cognitive deficiency remains scarce, current findings indicate that pro-inflammatory processes indeed result in exacerbation of several domains of cognitive deterioration. Interestingly, microglia, the immune cells of the brain, appear to exert initial compensatory neuroprotective functionalities upon acute ethanol exposure while chronic alcohol intake seems to attenuate these responses and overall microglial activity.

          Conclusion: As these results indicate inflammation to be of importance in cognitive impairment following alcohol consumption and might as such provide alternate therapeutic avenues, a considerable increase in research efforts in this domain is urgently required.

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          Most cited references38

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          Prevalence of 12-Month Alcohol Use, High-Risk Drinking, and DSM-IV Alcohol Use Disorder in the United States, 2001-2002 to 2012-2013

          Lack of current and comprehensive trend data derived from a uniform, reliable, and valid source on alcohol use, high-risk drinking, and DSM-IV alcohol use disorder (AUD) represents a major gap in public health information.
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            Widespread and sustained cognitive deficits in alcoholism: a meta-analysis.

            The cognitive repercussions of alcohol dependence are well documented. However, the literature remains somewhat ambiguous with respect to which distinct cognitive functions are more susceptible to impairment in alcoholism and to how duration of abstinence affects cognitive recovery. Some theories claim alcohol negatively affects specific cognitive functions, while others assert that deficits are more diffuse in nature. This is the first meta-analysis to examine cognition in alcohol abuse/dependence and the duration of abstinence necessary to achieve cognitive recovery. A literature search yielded 62 studies that assessed cognitive dysfunction among alcoholics. Effect size estimates were calculated using the Comprehensive Meta-Analysis V2, for the following 12 cognitive domains: intelligence quotient, verbal fluency/language, speed of processing, working memory, attention, problem solving/executive functions, inhibition/impulsivity, verbal learning, verbal memory, visual learning, visual memory and visuospatial abilities. Within these 12 domains, three effect size estimates were calculated based on abstinence duration. The three groups were partitioned into short- ( 1 year) term abstinence. Findings revealed moderate impairment across 11 cognitive domains during short-term abstinence, with moderate impairment across 10 domains during intermediate term abstinence. Small effect size estimates were found for long-term abstinence. These results suggest significant impairment across multiple cognitive functions remains stable during the first year of abstinence from alcohol. Generally, dysfunction abates by 1 year of sobriety. These findings support the diffuse brain hypothesis and suggest that cognitive dysfunction may linger for up to an average of 1 year post-detoxification from alcohol. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.
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              Kynurenines in CNS disease: regulation by inflammatory cytokines

              The kynurenine pathway (KP) metabolizes the essential amino acid tryptophan and generates a number of neuroactive metabolites collectively called the kynurenines. Segregated into at least two distinct branches, often termed the “neurotoxic” and “neuroprotective” arms of the KP, they are regulated by the two enzymes kynurenine 3-monooxygenase and kynurenine aminotransferase, respectively. Interestingly, several enzymes in the pathway are under tight control of inflammatory mediators. Recent years have seen a tremendous increase in our understanding of neuroinflammation in CNS disease. This review will focus on the regulation of the KP by inflammatory mediators as it pertains to neurodegenerative and psychiatric disorders.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                12 September 2019
                2019
                : 10
                : 632
                Affiliations
                [1] 1Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp , Antwerp, Belgium
                [2] 2Scientific Initiative of Neuropsychiatric and Psychopharmacological Studies (SINAPS), University Department of Psychiatry , Duffel, Belgium
                [3] 3Department of Addiction, Psychiatric Hospital Multiversum , Boechout, Belgium
                Author notes

                Edited by: Hamed Ekhtiari, Laureate Institute for Brain Research, United States

                Reviewed by: Roberto Colangeli, University of Calgary, Canada; Benjamin Rolland, Université de Lyon, France

                *Correspondence: Geert Dom, geert.dom@ 123456uantwerpen.be

                This article was submitted to Addictive Disorders, a section of the journal Frontiers in Psychiatry

                †These authors have contributed equally to this work.

                Article
                10.3389/fpsyt.2019.00632
                6751886
                31156488
                9158fb19-ee56-477a-b6c6-29435ed97943
                Copyright © 2019 Coppens, Morrens, Destoop and Dom

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 09 January 2019
                : 06 August 2019
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 52, Pages: 8, Words: 3875
                Categories
                Psychiatry
                Systematic Review

                Clinical Psychology & Psychiatry
                inflammation,alcohol use disorder,cognition,alcohol addiction,psychiatry

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