Meta-analysis of grey matter changes and their behavioral characterization in patients with alcohol use disorder

Spindler, Carolin; Trautmann, Sebastian; Alexander, Nina; Bröning, Sonja; Bartscher, Sarah; Stuppe, Markus; Muehlhan, Markus

doi:10.1038/s41598-021-84804-7

Cited by 19 publications

(12 citation statements)

References 99 publications

(110 reference statements)

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“…In summary, the above examples point towards an association of WM changes in AUD patients identified by this meta-analysis and several behavioral impairments. Together with previously reported GM reductions in AUD [ 18 ], they may explain the deterioration of a wide range of motor, cognitive, affective, and perceptual functions in individuals with AUD. However, the behavioral interpretation of our results is still speculative as it is based on a few single studies and as we could not apply a data-driven approach that is comparable to the workflows via the BrainMap database for GM data [ 79 ].…”

Section: Discussionsupporting

confidence: 74%

“…Structural brain alterations in AUD have been investigated in a large number of neuroimaging studies. Regarding GM changes, several meta-analyses highlighted specific patterns of reduced regional brain volume or density [ 16 – 18 ]. In recent years, the number of studies investigating the macro- and microstructure of WM by magnetic resonance imaging (MRI) methods has also increased.…”

Section: Introductionmentioning

confidence: 99%

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A coordinate-based meta-analysis of white matter alterations in patients with alcohol use disorder

et al. 2022

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Introduction: Besides the commonly described gray matter (GM) deficits, there is growing evidence of significant white matter (WM) alterations in patients with alcohol use disorder (AUD). WM changes can be assessed using volumetric and diffusive magnetic resonance imaging methods, such as voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). The aim of the present meta-analysis is to investigate the spatial convergence of the reported findings on WM alterations in AUD. Methods: Systematic literature search on PubMed and further databases revealed 18 studies eligible for inclusion, entailing a total of 462 AUD patients and 416 healthy controls (up to January 18, 2021). All studies that had used either VBM or DTI whole-brain analyzing methods and reported results as peak-coordinates in standard reference space were considered for inclusion. We excluded studies using approaches non-concordant with recent guidelines for neuroimaging meta-analyses and studies investigating patient groups with Korsakoff syndrome or other comorbid substance use disorders (except tobacco). Results: Anatomical likelihood estimation (ALE) revealed four significant clusters of convergent macro- and microstructural WM alterations in AUD patients that were assigned to the genu and body of the corpus callosum, anterior and posterior cingulum, fornix, and the right posterior limb of the internal capsule. Discussion: The changes in WM could to some extent explain the deteriorations in motor, cognitive, affective, and perceptual functions seen in AUD. Future studies are needed to clarify how WM alterations vary over the course of the disorder and to what extent they are reversible with prolonged abstinence.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

A coordinate-based meta-analysis of white matter alterations in patients with alcohol use disorder

et al. 2022

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“…Continuous consumption of alcohol in high levels can lead to long-term functional changes such as impairments in visuo-spatial functioning [ 49 ]. Functional impairments in alcohol abuse can be explained by the changes in grey matter structure, resulting from the neurotoxicity of alcohol in chronic high consumption patterns [ 50 ]. Several studies have showed that in alcohol abuse patients the grey matter volume reduced as compared to healthy controls.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, Saito et al reported changes in the count of glial cells after chronic ethanol exposure [ 52 ]. Together, these findings indicate that alcohol consumption causes a decline in grey matter size in certain brain regions and has effects on the behavioral depiction of these brain areas that may lead to cognitive impairment [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study

et al. 2022

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Alcoholism is one of the most common diseases that can lead to the development of several chronic diseases including steatosis, and cognitive dysfunction. Statins are lipid-lowering drugs that are commonly prescribed for patients with fatty liver diseases; however, the exact effect of statins on cognitive function is still not fully understood. In the present study, we have investigated the molecular and microscopic basis of cognitive impairment induced by alcohol and/or Atorvastatin (ATOR) administration to male Wistar albino rats and explored the possible protective effect of acetylsalicylic acid (ASA). The biochemical analysis indicated that either alcohol or ATOR or together in combination produced a significant increase in the nucleotide-binding domain–like receptor 3 (NLRP3), interleukin-1β (IL-1β) miRNA155 expression levels in the frontal cortex of the brain tissue. The histological and morphometric analysis showed signs of degeneration in the neurons and the glial cells with aggregations of inflammatory cells and a decrease in the mean thickness of the frontal cortex. Immunohistochemical analysis showed a significant increase in the caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex. Interestingly, administration of ASA reversed the deleterious effect of the alcohol and ATOR intake and improved the cognitive function as indicated by biochemical and histological analysis. ASA significantly decreased the expression levels of miRNA155, NLRP3, and IL1B, and produced a significant decrease in caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex with a reduction in the process of neuroinflammation and neuronal damage. To further investigate these findings, we have performed an extensive molecular docking study to investigate the binding affinity of ASA to the binding pockets of the NLRP3 protein. Our results indicated that ASA has high binding scores toward the active sites of the NLRP3 NACHT domain with the ability to bind to the NLRP3 pockets by a set of hydrophilic and hydrophobic interactions. Taken together, the present study highlights the protective pharmacological effect of ASA to attenuate the deleterious effect of alcohol intake and long term ATOR therapy on the cognitive function via targeting miRNA155 and NLRP3 proteins.

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“…Recently, meta-analysis study on the structural findings of AUD using an effect-size based meta-analytical approach demonstrated significant GM reductions in the corticostriatal-limbic circuits including the key areas of the triple networks, such as DLPFC, hippocampus, bilateral insula, and ACC compared to healthy controls ( 9 ). Another study applying a different methodology (i.e., Anatomical Likelihood Estimation) also found gray matter reduction in the insula, ACC, and DLPFC, and demonstrated the association between volume reduction and functional impairment including cognition, emotion, and perception ( 28 ). This finding suggests that the gray matter reduction of the areas in the triple networks could be associated with cognitive and affective impairment observed in patients with AUD.…”

Section: Introductionmentioning

confidence: 98%

Functional and Structural Alteration of Default Mode, Executive Control, and Salience Networks in Alcohol Use Disorder

2021

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Alcohol use disorder (AUD) has been related to aberrant functional connectivity (FC) in the salience network (SN), executive control network (ECN), and default mode network (DMN). However, there is a lack of comprehensive and simultaneous examination of these networks in patients with AUD and of their relation to potential anatomical changes. We aimed to comprehensively examine the alteration in FC in the three networks in AUD patients, and the correlation of the alteration with anatomical/structural changes (volume) in the neural areas implicated in these networks, by applying voxel-based morphometry (VBM) and region of interest-to-region of interest connectivity analysis simultaneously. In all, 22 patients with AUD and 22 healthy adults participated in the study and underwent T1 magnetic resonance imaging. Patients with AUD showed increased FCs within the DMN and SN networks, especially in terms of connectivity of the frontal areas and bilateral hippocampi. They also showed decreased FCs in the ECN. In addition, there was significant volume reduction in these areas (frontal areas and hippocampus). The increased FCs within the frontal areas or bilateral hippocampi showed a negative correlation with gray matter volume of these areas in AUD patients. Our findings add to the empirical evidence that the frontal lobe and hippocampi are critical areas that are vulnerable to functional and structural changes due to AUD.

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Meta-analysis of grey matter changes and their behavioral characterization in patients with alcohol use disorder

Cited by 19 publications

References 99 publications

A coordinate-based meta-analysis of white matter alterations in patients with alcohol use disorder

A coordinate-based meta-analysis of white matter alterations in patients with alcohol use disorder

Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study

Functional and Structural Alteration of Default Mode, Executive Control, and Salience Networks in Alcohol Use Disorder

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