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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Carolien G.F. de Kovel; Lyubomir I. Aftanas; André Aleman; Aaron Alexander-Bloch; +74 Authors

    Objective: Asymmetry is a subtle but pervasive aspect of the human brain, and it may be altered in several psychiatric conditions. MRI studies have shown subtle differences of brain anatomy between people with major depressive disorder and healthy control subjects, but few studies have specifically examined brain anatomical asymmetry in relation to this disorder, and results from those studies have remained inconclusive. At the functional level, some electroencephalography studies have indicated left fronto-cortical hypoactivity and right parietal hypoactivity in depressive disorders, so aspects of lateralized anatomy may also be affected. The authors used pooled individual-level data from data sets collected around the world to investigate differences in laterality in measures of cortical thickness, cortical surface area, and subcortical volume between individuals with major depression and healthy control subjects.Methods: The authors investigated differences in the laterality of thickness and surface area measures of 34 cerebral cortical regions in 2,256 individuals with major depression and 3,504 control subjects from 31 separate data sets, and they investigated volume asymmetries of eight subcortical structures in 2,540 individuals with major depression and 4,230 control subjects from 32 data sets. T-1-weighted MRI data were processedwith a single protocol using FreeSurfer and the Desikan-Killiany atlas. The large sample size provided 80% power to detect effects of the order of Cohen's d=0.1.Results: The largest effect size (Cohen's d) of major depression diagnosis was 0.085 for the thickness asymmetry of the superior temporal cortex, which was not significant after adjustment for multiple testing. Asymmetry measures were not significantly associated with medication use, acute compared with remitted status, first episode compared with recurrent status, or age at onset.Conclusions: Altered brain macro-anatomical asymmetry may be of little relevance to major depression etiology in most cases.

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    MPG.PuRe
    Article . 2019
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    NARCIS
    Article . 2019
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    American Journal of Psychiatry
    Article . 2019
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    DZNE Pub
    Article . 2019
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ NARCIS; American Jou...arrow_drop_down
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      Article . 2019
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      Article . 2019
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      American Journal of Psychiatry
      Article . 2019
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      DZNE Pub
      Article . 2019
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Patricia Blanchet; Martina Bebin; Shaam Bruet; Gregory M Cooper; +15 Authors

    Deletions at chromosome 2p25.3 are associated with a syndrome consisting of intellectual disability and obesity. The smallest region of overlap for deletions at 2p25.3 contains PXDN and MYT1L. MYT1L is expressed only within the brain in humans. We hypothesized that single nucleotide variants (SNVs) in MYT1L would cause a phenotype resembling deletion at 2p25.3. To examine this we sought MYT1L SNVs in exome sequencing data from 4, 296 parent-child trios. Further variants were identified through a genematcher-facilitated collaboration. We report 9 patients with MYT1L SNVs (4 loss of function and 5 missense). The phenotype of SNV carriers overlapped with that of 2p25.3 deletion carriers. To identify the transcriptomic consequences of MYT1L loss of function we used CRISPR-Cas9 to create a knockout cell line. Gene Ontology analysis in knockout cells demonstrated altered expression of genes that regulate gene expression and that are localized to the nucleus. These differentially expressed genes were enriched for OMIM disease ontology terms “mental retardation”. To study the developmental effects of MYT1L loss of function we created a zebrafish knockdown using morpholinos. Knockdown zebrafish manifested loss of oxytocin expression in the preoptic neuroendocrine area. This study demonstrates that MYT1L variants are associated with syndromic obesity in humans. The mechanism is related to dysregulated expression of neurodevelopmental genes and altered development of the neuroendocrine hypothalamus. Author summary Intellectual disability is defined by having an intelligence quotient of less than 70 points, and it affects about 2–3 people in every 100. Obesity is defined as having a body mass index of over 30 in adults or over the 95th centile in children. Both of these conditions are major public health concerns in Western countries. Genetic studies have shown that small missing pieces of chromosome (deletions, which remove many genes) and changes to the lettering of genes (which stop the gene from working, mutations) can cause intellectual disability or obesity. Here we identified 9 children with intellectual disability and obesity who have mutations in a gene called MYT1L. This gene is thought to give an important instruction for brain development. To find out what the effect of loss of MYT1L is on brain development we reduced the levels of MYT1L (using a special chemical) in an experimental zebrafish. This showed that loss of MYT1L in zebrafish causes a problem with the development of the hypothalamus, which may explain how MYT1L mutations cause obesity in humans. In the zebrafish there was also reduction of a brain hormone called oxytocin which is involved in thought processes, which may explain why MYT1L mutations cause intellectual disability. We have identified a new genetic condition caused by MYT1L mutations, further study of this gene will help us understand, and treat, intellectual disability and obesity.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    PLoS Genetics
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    PLoS Genetics
    Article . 2017 . Peer-reviewed
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    PLoS Genetics
    Article . 2017
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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      PLoS Genetics
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      PLoS Genetics
      Article . 2017 . Peer-reviewed
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      PLoS Genetics
      Article . 2017
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    Authors: Michael, Fritz; Anna M, Klawonn; Anna, Nilsson; Anand Kumar, Singh; +17 Authors

    Systemic inflammation causes malaise and general feelings of discomfort. This fundamental aspect of the sickness response reduces the quality of life for people suffering from chronic inflammatory diseases and is a nuisance during mild infections like common colds or the flu. To investigate how inflammation is perceived as unpleasant and causes negative affect, we used a behavioral test in which mice avoid an environment that they have learned to associate with inflammation-induced discomfort. Using a combination of cell-type–specific gene deletions, pharmacology, and chemogenetics, we found that systemic inflammation triggered aversion through MyD88-dependent activation of the brain endothelium followed by COX1-mediated cerebral prostaglandin E2 (PGE2) synthesis. Further, we showed that inflammation-induced PGE2 targeted EP1 receptors on striatal dopamine D1 receptor–expressing neurons and that this signaling sequence induced aversion through GABA-mediated inhibition of dopaminergic cells. Finally, we demonstrated that inflammation-induced aversion was not an indirect consequence of fever or anorexia but that it constituted an independent inflammatory symptom triggered by a unique molecular mechanism. Collectively, these findings demonstrate that PGE2-mediated modulation of the dopaminergic motivational circuitry is a key mechanism underlying the negative affect induced by inflammation.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ The Journal of Clini...arrow_drop_down
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    The Journal of Clinical Investigation
    Article . 2015 . Peer-reviewed
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    Europe PubMed Central
    Other literature type . 2015
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      The Journal of Clinical Investigation
      Article . 2015 . Peer-reviewed
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      Europe PubMed Central
      Other literature type . 2015
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    Authors: Donal J, Cox; Robert H, Field; David G, Williams; Marcin, Baran; +3 Authors

    PUBLISHED The detection of nucleic acids by the innate immune system is an essential host response during viral infection. In recent years, a number of immune sensors capable of recognizing cytosolic DNA have been identified and include the PYHIN family members AIM2, IFI16, and p204 as well as the enzyme, cGAS. Activation of these receptors leads to the induction of antiviral genes including Type-1 interferons and chemokines such as CCL5. We have carried out extensive expression profiling of these DNA sensors and other members of the PYHIN family in highly purified primary astrocytes and microglia and have demonstrated that both cell types express the majority of these proteins at the mRNA level. In microglia, several family members are highly upregulated in response to IFN-? treatment while both cell types induce robust proinflammatory and antiviral cytokine production (e.g., IL-6, CCL5, IFN-?) in the presence of immune stimulatory DNA and RNA. The production of IL-6 is partially dependent on the interferon receptor as is IFN-? itself. Furthermore, we have found that p204 and AIM2 are upregulated in a Type I IFN dependent fashion in vivo, in a murine model of chronic neurodegeneration. Given the propensity of inflammatory responses to cause neuronal damage, increased expression and activation of these receptors, not only during viral infection but also during sterile inflammatory responses, has the potential to exacerbate existing neuroinflammation leading to further damage and impaired neurogenesis. GLIA 2015;63:812?825 Wellcome Trust, the Programme for Research in Third Level Institutions (PRTLI), European Regional Development Fund, the HEA

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    Glia
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    Glia
    Article . 2015 . Peer-reviewed
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      Glia
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      Glia
      Article . 2015 . Peer-reviewed
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    Authors: Nicolas Coquelet; Alison Mary; Philippe Peigneux; Serge Goldman; +2 Authors

    Functional magnetic resonance imaging (fMRI) studies report age-related changes in resting-state functional connectivity (rsFC), suggesting altered or reorganized connectivity patterns with age. However, age-related changes in neurovascular coupling might also partially account for altered connectivity patterns. Here, we used resting-state magnetoencephalography (MEG) and a connectome approach in carefully selected healthy young adults and elders. The MEG connectome was estimated as rsFC matrices involving forty nodes from six major resting-state networks. Source-level rsFC maps were computed in relevant frequency bands using leakage-corrected envelope correlations. Group differences were statistically assessed using non-parametric permutation tests. Our results failed to evidence significant age-related differences after correction for multiple comparisons in the α and the β bands both for static and dynamic rsFC, suggesting that the electrophysiological connectome is maintained in healthy ageing. Further studies should compare the evolution of the human brain connectome as estimated using fMRI and MEG in same healthy young and elder adults, as well as in ageing conditions associated with cognitive decline. At present, our results are in agreement with the brain maintenance theory for successful aging as they suggest that preserved intrinsic functional brain integration contributes to preserved cognitive functioning in healthy elders. info:eu-repo/semantics/published SCOPUS: ar.j

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Scientific Reports
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    Scientific Reports
    Article . 2017
    Data sources: DOAJ-Articles
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    Scientific Reports
    Article . 2017 . Peer-reviewed
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    DI-fusion
    Article . 2017 . Peer-reviewed
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      Scientific Reports
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      Scientific Reports
      Article . 2017
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      Scientific Reports
      Article . 2017 . Peer-reviewed
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      DI-fusion
      Article . 2017 . Peer-reviewed
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    Authors: Rocha-Rego, V.; Jogia, J.; Marquand, A.F.; Mourao-Miranda, J.; +2 Authors

    BackgroundBipolar disorder (BD) is one of the leading causes of disability worldwide. Patients are further disadvantaged by delays in accurate diagnosis ranging between 5 and 10 years. We applied Gaussian process classifiers (GPCs) to structural magnetic resonance imaging (sMRI) data to evaluate the feasibility of using pattern recognition techniques for the diagnostic classification of patients with BD.MethodGPCs were applied to gray (GM) and white matter (WM) sMRI data derived from two independent samples of patients with BD (cohort 1: n = 26; cohort 2: n = 14). Within each cohort patients were matched on age, sex and IQ to an equal number of healthy controls.ResultsThe diagnostic accuracy of the GPC for GM was 73% in cohort 1 and 72% in cohort 2; the sensitivity and specificity of the GM classification were respectively 69% and 77% in cohort 1 and 64% and 99% in cohort 2. The diagnostic accuracy of the GPC for WM was 69% in cohort 1 and 78% in cohort 2; the sensitivity and specificity of the WM classification were both 69% in cohort 1 and 71% and 86% respectively in cohort 2. In both samples, GM and WM clusters discriminating between patients and controls were localized within cortical and subcortical structures implicated in BD.ConclusionsOur results demonstrate the predictive value of neuroanatomical data in discriminating patients with BD from healthy individuals. The overlap between discriminative networks and regions implicated in the pathophysiology of BD supports the biological plausibility of the classifiers.

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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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    Psychological Medicine
    Article . 2013 . Peer-reviewed
    License: CC BY NC SA
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    Psychological Medicine
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    NARCIS
    Article . 2014
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      Psychological Medicine
      Article . 2013 . Peer-reviewed
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      Psychological Medicine
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      NARCIS
      Article . 2014
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    Authors: Franke, Barbara; Stein, Jason L; McIntosh, Andrew M; Eichhammer, Peter; +289 Authors

    Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. peerReviewed final draft Article

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    UEF eRepository
    Article . 2016 . Peer-reviewed
    Data sources: UEF eRepository
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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    Article . 2016
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    NARCIS
    Article . 2016
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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    Article . 2016
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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    Article . 2016
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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    Article . 2016
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    Article . 2016
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    Article . 2016
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      Article . 2016 . Peer-reviewed
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      Article . 2016
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      Article . 2016
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      Article . 2016
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      Article . 2016
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      Article . 2016
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      Article . 2016
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Slater, R; Hartley, C; Moultrie, F; Adams, E; +8 Authors

    Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants. A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP) screening and heel lancing provides effective analgesia. 156 infants between 34 and 42 weeks’ gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg) or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration. The primary outcome will be the Premature Infant Pain Profile–revised (PIPP-R) score during the 30 second periods after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2017 . Peer-reviewed
    Data sources: PubMed Central
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    Oxford University Research Archive
    Other literature type . 2017
    License: CC BY
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    Wellcome Open Research
    Article . 2017 . Peer-reviewed
    License: CC BY
    Data sources: Crossref
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    Wellcome Open Research
    Article . 2016 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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      Wellcome Open Research
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    Authors: María Mercedes Cobo; Caroline Hartley; Deniz Gursul; Foteini Andritsou; +12 Authors

    eLife digest Hospitalized newborns often undergo medical procedures, like blood tests, without pain relief. This can cause the baby to experience short-term distress that may have negative consequences later in life. However, testing the effects of pain relief in newborns is challenging because, unlike adults, they cannot report how much pain they are experiencing. One way to overcome this is to record the brain activity of newborns during a painful procedure and to see how these signals are modified following pain relief. Randomized controlled trials are the gold standard for these kinds of medical assessments, but require a high number of participants to account for individual differences in how babies respond to pain. Finding ways to reduce the size of pain control studies could lead to faster development of pain relief methods. Here, Cobo, Hartley et al. demonstrate a way to reduce the number of newborns needed to test potential pain-relieving interventions. In the experiments, the brain activity of nine babies was measured after a gentle poke and after a painful clinically required procedure. Cobo, Hartley et al. found that the babies’ response to the gentle poke correlated with their response to pain. Further data analysis revealed that this information can be used to predict the variability in pain experienced by different newborns, reducing the number of participants needed for pain relief trials. Next, Cobo, Hartley et al. used this new approach in two pilot tests. One showed that gently stroking an infant’s leg before blood is drawn from their heel reduced their brains’ response to pain. The second showed that giving a baby the painkiller paracetamol lessened the brain’s response to immunisation. The new approach identified by Cobo, Hartley et al. may enable smaller studies that can more quickly identify ways to reduce pain in babies. Furthermore, this work suggests that gentle brushing and paracetamol could provide pain relief for newborns undergoing hospital acute procedures. However, more formal clinical trials are needed to test the effectiveness of these two strategies. Despite the high burden of pain experienced by hospitalised neonates, there are few analgesics with proven efficacy. Testing analgesics in neonates is experimentally and ethically challenging and minimising the number of neonates required to demonstrate efficacy is essential. EEG (electroencephalography)-derived measures of noxious-evoked brain activity can be used to assess analgesic efficacy; however, as variability exists in neonate’s responses to painful procedures, large sample sizes are often required. Here, we present an experimental paradigm to account for individual differences in noxious-evoked baseline sensitivity which can be used to improve the design of analgesic trials in neonates. The paradigm is developed and tested across four observational studies using clinical, experimental, and simulated data (92 neonates). We provide evidence of the efficacy of gentle brushing and paracetamol, substantiating the need for randomised controlled trials of these interventions. This work provides an important step towards safe, cost-effective clinical trials of analgesics in neonates.

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    DOAJ-Articles
    Article . 2021
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    eLife
    Article . 2021 . Peer-reviewed
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