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Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts / B. G. MCKENNA in Molecular Autism, 12 (2021)
[article]
Titre : Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts Type de document : Texte imprimé et/ou numérique Auteurs : B. G. MCKENNA, Auteur ; Y. HUANG, Auteur ; K. VERVIER, Auteur ; D. HOFAMMANN, Auteur ; M. CAFFERATA, Auteur ; S. AL-MOMANI, Auteur ; F. LOWENTHAL, Auteur ; A. ZHANG, Auteur ; J. Y. KOH, Auteur ; S. THENUWARA, Auteur ; L. BRUEGGEMAN, Auteur ; E. BAHL, Auteur ; T. KOOMAR, Auteur ; N. POTTSCHMIDT, Auteur ; T. KALMUS, Auteur ; L. CASTEN, Auteur ; T. R. THOMAS, Auteur ; J. J. MICHAELSON, Auteur Article en page(s) : 43 p. Langues : Anglais (eng) Mots-clés : Androgen exposure Autism spectrum disorder Masculinity Neurodevelopment Social functioning Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) display a strong male bias. Androgen exposure is profoundly increased in typical male development, but it also varies within the sexes, and previous work has sought to connect morphological proxies of androgen exposure, including digit ratio and facial morphology, to neurodevelopmental outcomes. The results of these studies have been mixed, and the relationships between androgen exposure and behavior remain unclear. METHODS: Here, we measured both digit ratio masculinity (DRM) and facial landmark masculinity (FLM) in the same neurodevelopmental cohort (N = 763) and compared these proxies of androgen exposure to clinical and parent-reported features as well as polygenic risk scores. RESULTS: We found that FLM was significantly associated with NDD diagnosis (ASD, ADHD, ID; all [Formula: see text]), while DRM was not. When testing for association with parent-reported problems, we found that both FLM and DRM were positively associated with concerns about social behavior ([Formula: see text], [Formula: see text]; [Formula: see text], [Formula: see text], respectively). Furthermore, we found evidence via polygenic risk scores (PRS) that DRM indexes masculinity via testosterone levels ([Formula: see text], [Formula: see text]), while FLM indexes masculinity through a negative relationship with sex hormone binding globulin (SHBG) levels ([Formula: see text], [Formula: see text]). Finally, using the SPARK cohort (N = 9419) we replicated the observed relationship between polygenic estimates of testosterone, SHBG, and social functioning ([Formula: see text], [Formula: see text], and [Formula: see text], [Formula: see text] for testosterone and SHBG, respectively). Remarkably, when considered over the extremes of each variable, these quantitative sex effects on social functioning were comparable to the effect of binary sex itself (binary male: [Formula: see text]; testosterone: [Formula: see text] from 0.1%-ile to 99.9%-ile; SHBG: [Formula: see text] from 0.1%-ile to 99.9%-ile). LIMITATIONS: In the devGenes and SPARK cohorts, our analyses rely on indirect, rather than direct measurement of androgens and related molecules. CONCLUSIONS: These findings and their replication in the large SPARK cohort lend support to the hypothesis that increasing net androgen exposure diminishes capacity for social functioning in both males and females. En ligne : http://dx.doi.org/10.1186/s13229-021-00450-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 12 (2021) . - 43 p.[article] Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts [Texte imprimé et/ou numérique] / B. G. MCKENNA, Auteur ; Y. HUANG, Auteur ; K. VERVIER, Auteur ; D. HOFAMMANN, Auteur ; M. CAFFERATA, Auteur ; S. AL-MOMANI, Auteur ; F. LOWENTHAL, Auteur ; A. ZHANG, Auteur ; J. Y. KOH, Auteur ; S. THENUWARA, Auteur ; L. BRUEGGEMAN, Auteur ; E. BAHL, Auteur ; T. KOOMAR, Auteur ; N. POTTSCHMIDT, Auteur ; T. KALMUS, Auteur ; L. CASTEN, Auteur ; T. R. THOMAS, Auteur ; J. J. MICHAELSON, Auteur . - 43 p.
Langues : Anglais (eng)
in Molecular Autism > 12 (2021) . - 43 p.
Mots-clés : Androgen exposure Autism spectrum disorder Masculinity Neurodevelopment Social functioning Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) display a strong male bias. Androgen exposure is profoundly increased in typical male development, but it also varies within the sexes, and previous work has sought to connect morphological proxies of androgen exposure, including digit ratio and facial morphology, to neurodevelopmental outcomes. The results of these studies have been mixed, and the relationships between androgen exposure and behavior remain unclear. METHODS: Here, we measured both digit ratio masculinity (DRM) and facial landmark masculinity (FLM) in the same neurodevelopmental cohort (N = 763) and compared these proxies of androgen exposure to clinical and parent-reported features as well as polygenic risk scores. RESULTS: We found that FLM was significantly associated with NDD diagnosis (ASD, ADHD, ID; all [Formula: see text]), while DRM was not. When testing for association with parent-reported problems, we found that both FLM and DRM were positively associated with concerns about social behavior ([Formula: see text], [Formula: see text]; [Formula: see text], [Formula: see text], respectively). Furthermore, we found evidence via polygenic risk scores (PRS) that DRM indexes masculinity via testosterone levels ([Formula: see text], [Formula: see text]), while FLM indexes masculinity through a negative relationship with sex hormone binding globulin (SHBG) levels ([Formula: see text], [Formula: see text]). Finally, using the SPARK cohort (N = 9419) we replicated the observed relationship between polygenic estimates of testosterone, SHBG, and social functioning ([Formula: see text], [Formula: see text], and [Formula: see text], [Formula: see text] for testosterone and SHBG, respectively). Remarkably, when considered over the extremes of each variable, these quantitative sex effects on social functioning were comparable to the effect of binary sex itself (binary male: [Formula: see text]; testosterone: [Formula: see text] from 0.1%-ile to 99.9%-ile; SHBG: [Formula: see text] from 0.1%-ile to 99.9%-ile). LIMITATIONS: In the devGenes and SPARK cohorts, our analyses rely on indirect, rather than direct measurement of androgens and related molecules. CONCLUSIONS: These findings and their replication in the large SPARK cohort lend support to the hypothesis that increasing net androgen exposure diminishes capacity for social functioning in both males and females. En ligne : http://dx.doi.org/10.1186/s13229-021-00450-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 Sexually dimorphic facial features vary according to level of autistic-like traits in the general population / S. Z. GILANI in Journal of Neurodevelopmental Disorders, 7-1 (December 2015)
[article]
Titre : Sexually dimorphic facial features vary according to level of autistic-like traits in the general population Type de document : Texte imprimé et/ou numérique Auteurs : S. Z. GILANI, Auteur ; D. W. TAN, Auteur ; S. N. RUSSELL-SMITH, Auteur ; M. T. MAYBERY, Auteur ; A. MIAN, Auteur ; P. R. EASTWOOD, Auteur ; F. SHAFAIT, Auteur ; M. GOONEWARDENE, Auteur ; Andrew J. O. WHITEHOUSE, Auteur Article en page(s) : p.14 Langues : Anglais (eng) Mots-clés : Autism Autism spectrum disorder Facial features Femininity Gender defiant disorder Hypermasculinisation Masculinity Raine study Index. décimale : PER Périodiques Résumé : BACKGROUND: In a recent study, Bejerot et al. observed that several physical features (including faces) of individuals with an autism spectrum disorder (ASD) were more androgynous than those of their typically developed counterparts, suggesting that ASD may be understood as a 'gender defiant' disorder. These findings are difficult to reconcile with the hypermasculinisation account, which proposes that ASD may be an exaggerated form of cognitive and biological masculinity. The current study extended these data by first identifying six facial features that best distinguished males and females from the general population and then examining these features in typically developing groups selected for high and low levels of autistic-like traits. METHODS: In study 1, three-dimensional (3D) facial images were collected from 208 young adult males and females recruited from the general population. Twenty-three facial distances were measured from these images and a gender classification and scoring algorithm was employed to identify a set of six facial features that most effectively distinguished male from female faces. In study 2, measurements of these six features were compared for groups of young adults selected for high (n = 46) or low (n = 66) levels of autistic-like traits. RESULTS: For each sex, four of the six sexually dimorphic facial distances significantly differentiated participants with high levels of autistic-like traits from those with low trait levels. All four features were less masculinised for high-trait males compared to low-trait males. Three of four features were less feminised for high-trait females compared to low-trait females. One feature was, however, not consistent with the general pattern of findings and was more feminised among females who reported more autistic-like traits. Based on the four significantly different facial distances for each sex, discriminant function analysis correctly classified 89.7% of the males and 88.9% of the females into their respective high- and low-trait groups. CONCLUSIONS: The current data provide support for Bejerot et al.'s androgyny account since males and females with high levels of autistic-like traits generally showed less sex-typical facial features than individuals with low levels of autistic-like traits. En ligne : http://dx.doi.org/10.1186/s11689-015-9109-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=347
in Journal of Neurodevelopmental Disorders > 7-1 (December 2015) . - p.14[article] Sexually dimorphic facial features vary according to level of autistic-like traits in the general population [Texte imprimé et/ou numérique] / S. Z. GILANI, Auteur ; D. W. TAN, Auteur ; S. N. RUSSELL-SMITH, Auteur ; M. T. MAYBERY, Auteur ; A. MIAN, Auteur ; P. R. EASTWOOD, Auteur ; F. SHAFAIT, Auteur ; M. GOONEWARDENE, Auteur ; Andrew J. O. WHITEHOUSE, Auteur . - p.14.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 7-1 (December 2015) . - p.14
Mots-clés : Autism Autism spectrum disorder Facial features Femininity Gender defiant disorder Hypermasculinisation Masculinity Raine study Index. décimale : PER Périodiques Résumé : BACKGROUND: In a recent study, Bejerot et al. observed that several physical features (including faces) of individuals with an autism spectrum disorder (ASD) were more androgynous than those of their typically developed counterparts, suggesting that ASD may be understood as a 'gender defiant' disorder. These findings are difficult to reconcile with the hypermasculinisation account, which proposes that ASD may be an exaggerated form of cognitive and biological masculinity. The current study extended these data by first identifying six facial features that best distinguished males and females from the general population and then examining these features in typically developing groups selected for high and low levels of autistic-like traits. METHODS: In study 1, three-dimensional (3D) facial images were collected from 208 young adult males and females recruited from the general population. Twenty-three facial distances were measured from these images and a gender classification and scoring algorithm was employed to identify a set of six facial features that most effectively distinguished male from female faces. In study 2, measurements of these six features were compared for groups of young adults selected for high (n = 46) or low (n = 66) levels of autistic-like traits. RESULTS: For each sex, four of the six sexually dimorphic facial distances significantly differentiated participants with high levels of autistic-like traits from those with low trait levels. All four features were less masculinised for high-trait males compared to low-trait males. Three of four features were less feminised for high-trait females compared to low-trait females. One feature was, however, not consistent with the general pattern of findings and was more feminised among females who reported more autistic-like traits. Based on the four significantly different facial distances for each sex, discriminant function analysis correctly classified 89.7% of the males and 88.9% of the females into their respective high- and low-trait groups. CONCLUSIONS: The current data provide support for Bejerot et al.'s androgyny account since males and females with high levels of autistic-like traits generally showed less sex-typical facial features than individuals with low levels of autistic-like traits. En ligne : http://dx.doi.org/10.1186/s11689-015-9109-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=347 Testing the extreme male brain hypothesis: Is autism spectrum disorder associated with a more male-typical brain? / L. VAN EIJK in Autism Research, 14-8 (August 2021)
[article]
Titre : Testing the extreme male brain hypothesis: Is autism spectrum disorder associated with a more male-typical brain? Type de document : Texte imprimé et/ou numérique Auteurs : L. VAN EIJK, Auteur ; B. P. ZIETSCH, Auteur Article en page(s) : p.1597-1608 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/complications/diagnostic imaging Autistic Disorder Brain/diagnostic imaging Connectome Female Humans Magnetic Resonance Imaging Male Sex Characteristics autism spectrum disorder brain diseases magnetic resonance imaging masculinity neuroimaging sex characteristics Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is more common in males than females and has been linked to male-typical behavior. Accordingly, the "Extreme Male Brain" hypothesis suggests that ASD is associated with an exaggeratedly male-typical brain. To test this hypothesis, we derived a data-driven measure of individual differences along a male-female dimension based on sex differences in subcortical brain shape (i.e., brain maleness) by training our algorithm on two population samples (Queensland Twin IMaging study and Human Connectome Project; combined N = 2153). We then applied this algorithm to two clinical datasets (Autism Brain Imaging Data Exchange I and II; ASD N = 1060; neurotypical controls N = 1166) to obtain a brain maleness score for each individual, representing maleness of their brain on a male-female continuum. Consistent with the Extreme Male Brain hypothesis, we found a higher mean brain maleness score in the ASD group than in controls (d = 0.20 [0.12-0.29]), parallel to higher scores for control males than control females (d = 1.17 [1.05-1.29]). Further, brain maleness was positively associated with autistic symptoms. We tested the possibility this finding was driven by the ASD group's larger brains than controls (d = 0.17 [0.08-0.25]), given that males had larger brains than females (d = 0.96 [0.84-1.07]). Indeed, after adjusting for differences in brain size, the brain maleness difference between the ASD group and controls disappeared, and no association with autistic symptoms remained (after controlling for multiple comparisons), suggesting greater maleness of the autistic brain is driven by brain size. Brain maleness may be influenced by the same factors that influence brain size. LAY SUMMARY: A popular theory proposes that individuals with autistic spectrum disorder (ASD) have an "extreme male brain", but this has not been subject to rigorous, direct tests. We developed a measure of individual differences along a male-female dimension and then derived this measure for 1060 individuals with ASD and 1166 neurotypical controls. Individuals with ASD had slightly more male-type brains. However, this difference is accounted for by males and individuals with ASD having relatively larger brains than females and controls, respectively. En ligne : http://dx.doi.org/10.1002/aur.2537 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449
in Autism Research > 14-8 (August 2021) . - p.1597-1608[article] Testing the extreme male brain hypothesis: Is autism spectrum disorder associated with a more male-typical brain? [Texte imprimé et/ou numérique] / L. VAN EIJK, Auteur ; B. P. ZIETSCH, Auteur . - p.1597-1608.
Langues : Anglais (eng)
in Autism Research > 14-8 (August 2021) . - p.1597-1608
Mots-clés : Autism Spectrum Disorder/complications/diagnostic imaging Autistic Disorder Brain/diagnostic imaging Connectome Female Humans Magnetic Resonance Imaging Male Sex Characteristics autism spectrum disorder brain diseases magnetic resonance imaging masculinity neuroimaging sex characteristics Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is more common in males than females and has been linked to male-typical behavior. Accordingly, the "Extreme Male Brain" hypothesis suggests that ASD is associated with an exaggeratedly male-typical brain. To test this hypothesis, we derived a data-driven measure of individual differences along a male-female dimension based on sex differences in subcortical brain shape (i.e., brain maleness) by training our algorithm on two population samples (Queensland Twin IMaging study and Human Connectome Project; combined N = 2153). We then applied this algorithm to two clinical datasets (Autism Brain Imaging Data Exchange I and II; ASD N = 1060; neurotypical controls N = 1166) to obtain a brain maleness score for each individual, representing maleness of their brain on a male-female continuum. Consistent with the Extreme Male Brain hypothesis, we found a higher mean brain maleness score in the ASD group than in controls (d = 0.20 [0.12-0.29]), parallel to higher scores for control males than control females (d = 1.17 [1.05-1.29]). Further, brain maleness was positively associated with autistic symptoms. We tested the possibility this finding was driven by the ASD group's larger brains than controls (d = 0.17 [0.08-0.25]), given that males had larger brains than females (d = 0.96 [0.84-1.07]). Indeed, after adjusting for differences in brain size, the brain maleness difference between the ASD group and controls disappeared, and no association with autistic symptoms remained (after controlling for multiple comparisons), suggesting greater maleness of the autistic brain is driven by brain size. Brain maleness may be influenced by the same factors that influence brain size. LAY SUMMARY: A popular theory proposes that individuals with autistic spectrum disorder (ASD) have an "extreme male brain", but this has not been subject to rigorous, direct tests. We developed a measure of individual differences along a male-female dimension and then derived this measure for 1060 individuals with ASD and 1166 neurotypical controls. Individuals with ASD had slightly more male-type brains. However, this difference is accounted for by males and individuals with ASD having relatively larger brains than females and controls, respectively. En ligne : http://dx.doi.org/10.1002/aur.2537 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449