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  • 1
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    Online Resource
    Data_Sheet_2.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Psychiatry Vol. 12 ( 2021-4-20)
    Details
    In: Frontiers in Psychiatry, Frontiers Media SA, Vol. 12 ( 2021-4-20)
    Abstract: Genetic markers of the endocannabinoid system have been linked to a variety of addiction-related behaviors that extend beyond cannabis use. In the current study we investigate the relationship between endocannabinoid (eCB) genetic markers and alcohol use disorder (AUD) in European adolescents (14–18 years old) followed in the IMAGEN study ( n = 2,051) and explore replication in a cohort of North American adolescents from Canadian Saguenay Youth Study (SYS) ( n = 772). Case-control status is represented by a score of more than 7 on the Alcohol Use Disorder Identification Test (AUDIT). First a set-based test method was used to examine if a relationship between the eCB system and AUDIT case/control status exists at the gene level. Using only SNPs that are both independent and significantly associated to case-control status, we perform Fisher's exact test to determine SNP level odds ratios in relation to case-control status and then perform logistic regressions as post-hoc analysis, while considering various covariates. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the most robust SNP×SNP interaction of the five eCB genes with positive AUDIT screen. While no gene-sets were significantly associated to AUDIT scores after correction for multiple tests, in the case/control analysis, 7 SNPs were significantly associated with AUDIT scores of & gt; 7 ( p & lt; 0.05; OR & lt;1). Two SNPs remain significant after correction by false discovery rate (FDR): rs9343525 in CNR1 (p corrected =0.042, OR = 0.73) and rs507961 in MGLL (p corrected = 0.043, OR = 0.78). Logistic regression showed that both rs9353525 ( CNR1 ) and rs507961 ( MGLL ) remained significantly associated with positive AUDIT screens ( p & lt; 0.01; OR & lt; 1) after correction for multiple covariables and interaction of covariable × SNP. This result was not replicated in the SYS cohort. The GMDR model revealed a significant three-SNP interaction ( p = 0.006) involving rs484061 ( MGLL ), rs4963307 ( DAGLA ), and rs7766029 ( CNR1 ) predicted case-control status, after correcting for multiple covariables in the IMAGEN sample. A binomial logistic regression of the combination of these three SNPs by phenotype in the SYS cohort showed a result in the same direction as seen in the IMAGEN cohort (BETA = 0.501, p = 0.06). While preliminary, the present study suggests that the eCB system may play a role in the development of AUD in adolescents.
    Type of Medium: Online Resource
    ISSN: 1664-0640
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fpsyt.2021.645746
    DOI: 10.3389/fpsyt.2021.645746.s001
    DOI: 10.3389/fpsyt.2021.645746.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2564218-2
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  • 2
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    Table_1.DOCX
    Frontiers Media SA ; 2019
    In:  Frontiers in Molecular Neuroscience Vol. 12 ( 2019-3-12)
    Details
    In: Frontiers in Molecular Neuroscience, Frontiers Media SA, Vol. 12 ( 2019-3-12)
    Type of Medium: Online Resource
    ISSN: 1662-5099
    URL: Article
    URL: Article
    DOI: 10.3389/fnmol.2019.00060
    DOI: 10.3389/fnmol.2019.00060.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2452967-9
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  • 3
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    Incomplete Hippocampal Inversion: A Comprehensive MRI Study of Over 2000 Subjects
    Frontiers Media SA ; 2015
    In:  Frontiers in Neuroanatomy Vol. 9 ( 2015-12-22)
    Details
    In: Frontiers in Neuroanatomy, Frontiers Media SA, Vol. 9 ( 2015-12-22)
    Type of Medium: Online Resource
    ISSN: 1662-5129
    URL: Article
    DOI: 10.3389/fnana.2015.00160
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2015
    detail.hit.zdb_id: 2452969-2
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  • 4
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    Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-6-9)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-6-9)
    Abstract: An estimated 20–25% of the population is affected by chronic, non-communicable inflammatory skin diseases. Chronic skin inflammation has many causes. Among the most frequent chronic inflammatory skin diseases are atopic dermatitis, psoriasis, urticaria, lichen planus, and hidradenitis suppurativa, driven by a complex interplay of genetics and environmental factors. Autoimmunity is another important cause of chronic skin inflammation. The autoimmune response may be mainly T cell driven, such as in alopecia areata or vitiligo, or B cell driven in chronic spontaneous urticaria, pemphigus and pemphigoid diseases. Rare causes of chronic skin inflammation are autoinflammatory diseases, or rheumatic diseases, such as cutaneous lupus erythematosus or dermatomyositis. Whilst we have seen a significant improvement in diagnosis and treatment, several challenges remain. Especially for rarer causes of chronic skin inflammation, early diagnosis is often missed because of low awareness and lack of diagnostics. Systemic immunosuppression is the treatment of choice for almost all of these diseases. Adverse events due to immunosuppression, insufficient therapeutic responses and relapses remain a challenge. For atopic dermatitis and psoriasis, a broad spectrum of innovative treatments has been developed. However, treatment responses cannot be predicted so far. Hence, development of (bio)markers allowing selection of specific medications for individual patients is needed. Given the encouraging developments during the past years, we envision that many of these challenges in the diagnosis and treatment of chronic inflammatory skin diseases will be thoroughly addressed in the future.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    DOI: 10.3389/fmed.2022.875492
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 5
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    Video_5.avi
    Frontiers Media SA ; 2021
    In:  Frontiers in Medicine Vol. 8 ( 2021-4-12)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2021-4-12)
    Abstract: Background: Interleukin-22 (IL-22) impacts the integrity of intestinal epithelia and has been associated with the development of colitis-associated cancer and inflammatory bowel diseases (IBD). Previous data suggest that IL-22 protects the mucosal barrier and promotes wound healing and barrier defect. We hypothesized, that IL-22 modulates cell polarity of intestinal epithelial cells (IECs) acting on tight junction assembly. The aim of the study was to investigate IL-22-dependent mechanisms in the reprogramming of intestinal epithelia. Methods: IECs were exposed to IL-22 at various concentrations. IECs in Matrigel® were grown to 3-dimensional cysts in the presence or absence of IL-22 and morphology and expression of polarity proteins were analyzed by confocal microscopy. Epithelial cell barrier (TER and sandwich assay) and TJ assembly analysis (calcium-switch assay) were performed. TJ and cell polarity protein expression were assessed by western blotting and confocal microscopy. Cell migration and invasion assays were performed. Induction of epithelial-mesenchymal transition (EMT) was assessed by RT-qPCR analysis and western blotting. Signaling pathway analyses were performed by phosphoblotting and functional assays after blocking STAT3 and ERK signaling pathways. Using the toxoplasma-model of terminal ileitis, IL-22-knock-out mice were compared to wild-type littermates, analyzed for barrier function using one-path-impedance-analysis and macromolecular flux (H3-mannitol, Ussing-chambers). Results: IECs exhibited a barrier defect after IL-22 exposure. TJ protein distribution and expression were severely impaired. Delayed recovery in the calcium-switch assay was observed suggesting a defect in TJ assembly. Analyzing the 3D-cyst model, IL-22 induced multi-lumen and aberrant cysts, and altered the localization of cell polarity proteins. Cell migration and invasion was caused by IL-22 as well as induction of EMT. Interestingly, only inhibition of the MAPK pathway, rescued the TJal barrier defect, while blocking STAT3 was relevant for cell survival. In addition, ileal mucosa of IL-22 deficient mice was protected from the barrier defect seen in Toxoplasma gondii-induced ileitis in wild type mice shown by significantly higher Re values and correspondingly lower macromolecule fluxes. Conclusion: IL-22 impairs intestinal epithelial cell barrier by inducing EMT, causing defects in epithelial cell polarity and increasing cell motility and cell invasion. IL-22 modulates TJ protein expression and mediates tight junctional (TJal) barrier defects via ERK pathway.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2021.656047
    DOI: 10.3389/fmed.2021.656047.s001
    DOI: 10.3389/fmed.2021.656047.s002
    DOI: 10.3389/fmed.2021.656047.s003
    DOI: 10.3389/fmed.2021.656047.s004
    DOI: 10.3389/fmed.2021.656047.s005
    DOI: 10.3389/fmed.2021.656047.s006
    DOI: 10.3389/fmed.2021.656047.s007
    DOI: 10.3389/fmed.2021.656047.s008
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2775999-4
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  • 6
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    Data_Sheet_1.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Systems Neuroscience Vol. 15 ( 2021-9-30)
    Details
    In: Frontiers in Systems Neuroscience, Frontiers Media SA, Vol. 15 ( 2021-9-30)
    Abstract: Adolescence is a period of vulnerability for the maturation of gray matter (GM) and also for the onset of psychiatric disorders such as major depressive disorder (MDD), bipolar disorder and schizophrenia. Chronic neuroinflammation is considered to play a role in the etiology of these illnesses. However, the involvement of neuroinflammation in the observed link between regional GM volume reductions and psychiatric symptoms is not established yet. Here, we investigated a possible common immune-related genetic link between these two phenomena in european adolescents recruited from the community. Hippocampal and medial prefrontal cortex (mPFC) were defined a priori as regions of interest (ROIs). Their GM volumes were extracted in 1,563 14-year-olds from the IMAGEN database. We found a set of 26 SNPs that correlated with the hippocampal volumes and 29 with the mPFC volumes at age 14. We formed two ROI-Related Immune-gene scores (RRI) with the inflammation SNPs that correlated to hippocampal GM volume and to mPFC GM volume. The predictive ability of both RRIs with regards to the presence of psychiatric symptoms at age 18 was investigated by correlating the RRIs with psychometric questionnaires obtained at age 18. The RRIs (but not control scores constructed with random SNPs) correlated with the presence of depressive symptoms, positive psychotic symptoms, and externalizing symptoms in later adolescence. In addition, the effect of childhood maltreatment, one of the major environmental risk factors for depression and other mental disorders, interacted with the RRI effect. We next sought to validate this finding by investigating our set of inflammatory genes in a translational animal model of early life adversity. Mice were subjected to a protocol of maternal separation at an early post-natal age. We evaluated depressive behaviors in separated and non-separated mice at adolescence and their correlations with the concomitant expression of our genes in whole blood samples. We show that in mice, early life adversity affected the expression of our set of genes in peripheral blood, and that levels of expression correlated with symptoms of negative affect in adolescence. Overall, our translational findings in adolescent mice and humans provide a novel validated gene-set of immune-related genes for further research in the early stages of mood disorders.
    Type of Medium: Online Resource
    ISSN: 1662-5137
    URL: Article
    URL: Article
    DOI: 10.3389/fnsys.2021.725413
    DOI: 10.3389/fnsys.2021.725413.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2453005-0
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  • 7
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    On doing multi-act arithmetic: A multitrait-multimethod approach of performance dimensions in integrated multitasking
    Frontiers Media SA ; 2022
    In:  Frontiers in Psychology Vol. 13 ( 2022-8-18)
    Details
    In: Frontiers in Psychology, Frontiers Media SA, Vol. 13 ( 2022-8-18)
    Abstract: Here we present a systematic plan to the experimental study of test–retest reliability in the multitasking domain, adopting the multitrait-multimethod (MTMM) approach to evaluate the psychometric properties of performance in Düker-type speeded multiple-act mental arithmetic. These form of tasks capacitate the experimental analysis of integrated multi-step processing by combining multiple mental operations in flexible ways in the service of the overarching goal of completing the task. A particular focus was on scoring methodology, particularly measures of response speed variability. To this end, we present data of two experiments with regard to (a) test–retest reliability, (b) between-measures correlational structure, (c) and stability (test–retest practice effects). Finally, we compared participants with high versus low performance variability to assess ability-related differences in measurement precision (typically used as proxy to “simulate” patient populations), which is especially relevant in the applied fields of clinical neuropsychology. The participants performed two classic integrated multi-act arithmetic tasks, combining addition and verification (Exp. 1) and addition and comparison (Exp. 2). The results revealed excellent test–retest reliability for the standard and the variability measures. The analysis of between-measures correlational structure revealed the typical pattern of convergent and discriminant relationships, and also, that absolute response speed variability was highly correlated with average speed ( r & gt; 0.85), indicating that these measures mainly deliver redundant information. In contrast, speed-adjusted (relativized) variability revealed discriminant validity being correlated to a much lesser degree with average speed, indicating that this measure delivers additional information not already provided by the speed measure. Furthermore, speed-adjusted variability was virtually unaffected by test–retest practice, which makes this measure interesting in situations with repeated testing.
    Type of Medium: Online Resource
    ISSN: 1664-1078
    URL: Article
    DOI: 10.3389/fpsyg.2022.946626
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2563826-9
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