Tackling hypo and hyper sensory processing heterogeneity in autism: From clinical stratification to genetic pathways / Julian TILLMANN ; Freddy CLIQUET ; Frédérique AMSELLEM ; Anna MARUANI ; Claire LEBLOND ; Anita BEGGIATO ; David GERMANAUD ; Anouck AMESTOY ; Myriam LY-LE MOAL ; Daniel UMBRICHT ; Christopher CHATHAM ; Lorraine MURTAGH ; Manuel BOUVARD ; Marion LEBOYER ; Tony CHARMAN ; Thomas BOURGERON ; Richard DELORME ; Guillaume DUMAS ; EU-AIMS LEAP Group in Autism Research, 16-2 (February 2023)  

Public ISBD [article]  inAutism Research > 16-2 (February 2023) . - p.364-378 Titre : Tackling hypo and hyper sensory processing heterogeneity in autism: From clinical stratification to genetic pathways Type de document : Texte imprimé et/ou numérique Auteurs : Julian TILLMANN, Auteur ; Freddy CLIQUET, Auteur ; Frédérique AMSELLEM, Auteur ; Anna MARUANI, Auteur ; Claire LEBLOND, Auteur ; Anita BEGGIATO, Auteur ; David GERMANAUD, Auteur ; Anouck AMESTOY, Auteur ; Myriam LY-LE MOAL, Auteur ; Daniel UMBRICHT, Auteur ; Christopher CHATHAM, Auteur ; Lorraine MURTAGH, Auteur ; Manuel BOUVARD, Auteur ; Marion LEBOYER, Auteur ; Tony CHARMAN, Auteur ; Thomas BOURGERON, Auteur ; Richard DELORME, Auteur ; Guillaume DUMAS, Auteur ; EU-AIMS LEAP Group, Auteur Article en page(s) : p.364-378 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Abstract As an integral part of autism spectrum symptoms, sensory processing issues including both hypo and hyper sensory sensitivities. These sensory specificities may result from an excitation/inhibition imbalance with a poorly understood of their level of convergence with genetic alterations in GABA-ergic and glutamatergic pathways. In our study, we aimed to characterize the hypo/hyper-sensory profile among autistic individuals. We then explored its link with the burden of deleterious mutations in a subset of individuals with available whole-genome sequencing data. To characterize the hypo/hyper-sensory profile, the differential Short Sensory Profile (dSSP) was defined as a normalized and centralized hypo/hypersensitivity ratio from the Short Sensory Profile (SSP). Including 1136 participants (533 autistic individuals, 210 first-degree relatives, and 267 controls) from two independent study samples (PARIS and LEAP), we observed a statistically significant dSSP mean difference between autistic individuals and controls, driven mostly by a high dSSP variability, with an intermediated profile represented by relatives. Our genetic analysis tended to associate the dSSP and the hyposensitivity with mutations of the GABAergic pathway. The major limitation was the dSSP difficulty to discriminate subjects with a similar quantum of hypo- and hyper-sensory symptoms to those with no such symptoms, resulting both in a similar ratio score of 0. However, the dSSP could be a relevant clinical score, and combined with additional sensory descriptions, genetics and endophenotypic substrates, will improve the exploration of the underlying neurobiological mechanisms of sensory processing differences in autism spectrum. En ligne : https://doi.org/10.1002/aur.2861 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=496 [article] Tackling hypo and hyper sensory processing heterogeneity in autism: From clinical stratification to genetic pathways [Texte imprimé et/ou numérique] / Julian TILLMANN, Auteur ; Freddy CLIQUET, Auteur ; Frédérique AMSELLEM, Auteur ; Anna MARUANI, Auteur ; Claire LEBLOND, Auteur ; Anita BEGGIATO, Auteur ; David GERMANAUD, Auteur ; Anouck AMESTOY, Auteur ; Myriam LY-LE MOAL, Auteur ; Daniel UMBRICHT, Auteur ; Christopher CHATHAM, Auteur ; Lorraine MURTAGH, Auteur ; Manuel BOUVARD, Auteur ; Marion LEBOYER, Auteur ; Tony CHARMAN, Auteur ; Thomas BOURGERON, Auteur ; Richard DELORME, Auteur ; Guillaume DUMAS, Auteur ; EU-AIMS LEAP Group, Auteur . - p.364-378. Langues : Anglais (eng) in Autism Research > 16-2 (February 2023) . - p.364-378 Index. décimale : PER Périodiques Résumé : Abstract As an integral part of autism spectrum symptoms, sensory processing issues including both hypo and hyper sensory sensitivities. These sensory specificities may result from an excitation/inhibition imbalance with a poorly understood of their level of convergence with genetic alterations in GABA-ergic and glutamatergic pathways. In our study, we aimed to characterize the hypo/hyper-sensory profile among autistic individuals. We then explored its link with the burden of deleterious mutations in a subset of individuals with available whole-genome sequencing data. To characterize the hypo/hyper-sensory profile, the differential Short Sensory Profile (dSSP) was defined as a normalized and centralized hypo/hypersensitivity ratio from the Short Sensory Profile (SSP). Including 1136 participants (533 autistic individuals, 210 first-degree relatives, and 267 controls) from two independent study samples (PARIS and LEAP), we observed a statistically significant dSSP mean difference between autistic individuals and controls, driven mostly by a high dSSP variability, with an intermediated profile represented by relatives. Our genetic analysis tended to associate the dSSP and the hyposensitivity with mutations of the GABAergic pathway. The major limitation was the dSSP difficulty to discriminate subjects with a similar quantum of hypo- and hyper-sensory symptoms to those with no such symptoms, resulting both in a similar ratio score of 0. However, the dSSP could be a relevant clinical score, and combined with additional sensory descriptions, genetics and endophenotypic substrates, will improve the exploration of the underlying neurobiological mechanisms of sensory processing differences in autism spectrum. En ligne : https://doi.org/10.1002/aur.2861 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=496

The neuroanatomical substrates of autism and ADHD and their link to putative genomic underpinnings / Caroline GURR ; Johanna LEYHAUSEN ; Hanna SEELEMEYER ; Anke BLETSCH ; Tim SCHAEFER ; Charlotte M. PRETZSCH ; Bethany OAKLEY ; Eva LOTH ; Dorothea L. FLORIS ; Jan K. BUITELAAR ; Christian F. BECKMANN ; Tobias BANASCHEWSKI ; Tony CHARMAN ; Emily J. H. JONES ; Julian TILLMANN ; Chris H CHATHAM ; Thomas BOURGERON ; EU-AIMS LEAP Group ; Declan G. M. MURPHY ; Christine ECKER in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 36 p. Titre : The neuroanatomical substrates of autism and ADHD and their link to putative genomic underpinnings Type de document : Texte imprimé et/ou numérique Auteurs : Caroline GURR, Auteur ; Johanna LEYHAUSEN, Auteur ; Hanna SEELEMEYER, Auteur ; Anke BLETSCH, Auteur ; Tim SCHAEFER, Auteur ; Charlotte M. PRETZSCH, Auteur ; Bethany OAKLEY, Auteur ; Eva LOTH, Auteur ; Dorothea L. FLORIS, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur ; Tobias BANASCHEWSKI, Auteur ; Tony CHARMAN, Auteur ; Emily J. H. JONES, Auteur ; Julian TILLMANN, Auteur ; Chris H CHATHAM, Auteur ; Thomas BOURGERON, Auteur ; EU-AIMS LEAP Group, Auteur ; Declan G. M. MURPHY, Auteur ; Christine ECKER, Auteur Article en page(s) : 36 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are neurodevelopmental conditions accompanied by differences in brain development. Neuroanatomical differences in autism are variable across individuals and likely underpin distinct clinical phenotypes. To parse heterogeneity, it is essential to establish how the neurobiology of ASD is modulated by differences associated with co-occurring conditions, such as attention-deficit/hyperactivity disorder (ADHD). This study aimed to (1) investigate between-group differences in autistic individuals with and without co-occurring ADHD, and to (2) link these variances to putative genomic underpinnings. METHODS: We examined differences in cortical thickness (CT) and surface area (SA) and their genomic associations in a sample of 533 individuals from the Longitudinal European Autism Project. Using a general linear model including main effects of autism and ADHD, and an ASD-by-ADHD interaction, we examined to which degree ADHD modulates the autism-related neuroanatomy. Further, leveraging the spatial gene expression data of the Allen Human Brain Atlas, we identified genes whose spatial expression patterns resemble our neuroimaging findings. RESULTS: In addition to significant main effects for ASD and ADHD in fronto-temporal, limbic, and occipital regions, we observed a significant ASD-by-ADHD interaction in the left precentral gyrus and the right frontal gyrus for measures of CT and SA, respectively. Moreover, individuals with ASD?+?ADHD differed in CT to those without. Both main effects and the interaction were enriched for ASD-but not for ADHD-related genes. LIMITATIONS: Although we employed a multicenter design to overcome single-site recruitment limitations, our sample size of N=25 individuals in the ADHD only group is relatively small compared to the other subgroups, which limits the generalizability of the results. Also, we assigned subjects into ADHD positive groupings according to the DSM-5 rating scale. While this is sufficient for obtaining a research diagnosis of ADHD, our approach did not take into account for how long the symptoms have been present, which is typically considered when assessing ADHD in the clinical setting. CONCLUSION: Thus, our findings suggest that the neuroanatomy of ASD is significantly modulated by ADHD, and that autistic individuals with co-occurring ADHD may have specific neuroanatomical underpinnings potentially mediated by atypical gene expression. En ligne : http://dx.doi.org/10.1186/s13229-023-00568-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] The neuroanatomical substrates of autism and ADHD and their link to putative genomic underpinnings [Texte imprimé et/ou numérique] / Caroline GURR, Auteur ; Johanna LEYHAUSEN, Auteur ; Hanna SEELEMEYER, Auteur ; Anke BLETSCH, Auteur ; Tim SCHAEFER, Auteur ; Charlotte M. PRETZSCH, Auteur ; Bethany OAKLEY, Auteur ; Eva LOTH, Auteur ; Dorothea L. FLORIS, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur ; Tobias BANASCHEWSKI, Auteur ; Tony CHARMAN, Auteur ; Emily J. H. JONES, Auteur ; Julian TILLMANN, Auteur ; Chris H CHATHAM, Auteur ; Thomas BOURGERON, Auteur ; EU-AIMS LEAP Group, Auteur ; Declan G. M. MURPHY, Auteur ; Christine ECKER, Auteur . - 36 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 36 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are neurodevelopmental conditions accompanied by differences in brain development. Neuroanatomical differences in autism are variable across individuals and likely underpin distinct clinical phenotypes. To parse heterogeneity, it is essential to establish how the neurobiology of ASD is modulated by differences associated with co-occurring conditions, such as attention-deficit/hyperactivity disorder (ADHD). This study aimed to (1) investigate between-group differences in autistic individuals with and without co-occurring ADHD, and to (2) link these variances to putative genomic underpinnings. METHODS: We examined differences in cortical thickness (CT) and surface area (SA) and their genomic associations in a sample of 533 individuals from the Longitudinal European Autism Project. Using a general linear model including main effects of autism and ADHD, and an ASD-by-ADHD interaction, we examined to which degree ADHD modulates the autism-related neuroanatomy. Further, leveraging the spatial gene expression data of the Allen Human Brain Atlas, we identified genes whose spatial expression patterns resemble our neuroimaging findings. RESULTS: In addition to significant main effects for ASD and ADHD in fronto-temporal, limbic, and occipital regions, we observed a significant ASD-by-ADHD interaction in the left precentral gyrus and the right frontal gyrus for measures of CT and SA, respectively. Moreover, individuals with ASD?+?ADHD differed in CT to those without. Both main effects and the interaction were enriched for ASD-but not for ADHD-related genes. LIMITATIONS: Although we employed a multicenter design to overcome single-site recruitment limitations, our sample size of N=25 individuals in the ADHD only group is relatively small compared to the other subgroups, which limits the generalizability of the results. Also, we assigned subjects into ADHD positive groupings according to the DSM-5 rating scale. While this is sufficient for obtaining a research diagnosis of ADHD, our approach did not take into account for how long the symptoms have been present, which is typically considered when assessing ADHD in the clinical setting. CONCLUSION: Thus, our findings suggest that the neuroanatomy of ASD is significantly modulated by ADHD, and that autistic individuals with co-occurring ADHD may have specific neuroanatomical underpinnings potentially mediated by atypical gene expression. En ligne : http://dx.doi.org/10.1186/s13229-023-00568-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

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