Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts / Brooke G. MCKENNA in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 43 p. Titre : Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts Type de document : texte imprimé Auteurs : Brooke G. MCKENNA, Auteur ; Ying HUANG, Auteur ; Kévin VERVIER, Auteur ; Dabney HOFAMMANN, Auteur ; Mary CAFFERATA, Auteur ; Seima AL-MOMANI, Auteur ; Florencia LOWENTHAL, Auteur ; Angela ZHANG, Auteur ; Jin-Young KOH, Auteur ; Savantha THENUWARA, Auteur ; Leo BRUEGGEMAN, Auteur ; Ethan BAHL, Auteur ; Tanner KOOMAR, Auteur ; Natalie POTTSCHMIDT, Auteur ; Taylor KALMUS, Auteur ; Lucas CASTEN, Auteur ; Taylor R. THOMAS, Auteur ; Jacob 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 [article] Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts [texte imprimé] / Brooke G. MCKENNA, Auteur ; Ying HUANG, Auteur ; Kévin VERVIER, Auteur ; Dabney HOFAMMANN, Auteur ; Mary CAFFERATA, Auteur ; Seima AL-MOMANI, Auteur ; Florencia LOWENTHAL, Auteur ; Angela ZHANG, Auteur ; Jin-Young KOH, Auteur ; Savantha THENUWARA, Auteur ; Leo BRUEGGEMAN, Auteur ; Ethan BAHL, Auteur ; Tanner KOOMAR, Auteur ; Natalie POTTSCHMIDT, Auteur ; Taylor KALMUS, Auteur ; Lucas CASTEN, Auteur ; Taylor R. THOMAS, Auteur ; Jacob 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

HPA-axis multilocus genetic profile score moderates the association between maternal prenatal perceived stress and offspring depression in early adulthood / Brooke G. MCKENNA in Development and Psychopathology, 33-1 (February 2021)  

Public ISBD [article]  inDevelopment and Psychopathology > 33-1 (February 2021) . - p.122-134 Titre : HPA-axis multilocus genetic profile score moderates the association between maternal prenatal perceived stress and offspring depression in early adulthood Type de document : texte imprimé Auteurs : Brooke G. MCKENNA, Auteur ; Constance HAMMEN, Auteur ; Patricia A. BRENNAN, Auteur Article en page(s) : p.122-134 Langues : Anglais (eng) Mots-clés : HPA Axis  depression  fetal programming  polygenic risk Index. décimale : PER Périodiques Résumé : Maternal stress during pregnancy can cause alterations to the fetal hypothalamus-pituitary-adrenal (HPA) axis, a phenomenon known as fetal programming that may have lasting effects on offspring outcomes, including depression. Evidence suggests that these effects may vary with respect to the offspring's genetic risk. Nonetheless, few studies have examined these effects into adulthood, when risk for depression onset is highest. The present study builds upon the extant literature by examining the interaction of maternal prenatal perceived stress (MPPS) and offspring HPA-axis polygenic risk to predict offspring depression in early adulthood. A total of 381 mother-child dyads participated in a prospective, longitudinal study that spanned from pregnancy until offspring were 20 years of age. Polygenic risk was defined by a multilocus genetic profile score (MGPS) that reflected the additive risk of three HPA-axis candidate genes. The results indicated that the interaction of MPPS and HPA-axis MGPS confers risk for offspring depression at age 20, in line with the differential susceptibility model. This interaction may be specific to prenatal stress, as maternal stress during early childhood did not interact with genetic risk to predict depression. These findings provide the first evidence that genetic variants that are associated with the HPA axis may act in a polygenic, additive fashion to moderate the association between fetal programming and adult depression. En ligne : http://dx.doi.org/10.1017/s0954579419001639 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] HPA-axis multilocus genetic profile score moderates the association between maternal prenatal perceived stress and offspring depression in early adulthood [texte imprimé] / Brooke G. MCKENNA, Auteur ; Constance HAMMEN, Auteur ; Patricia A. BRENNAN, Auteur . - p.122-134. Langues : Anglais (eng) in Development and Psychopathology > 33-1 (February 2021) . - p.122-134 Mots-clés : HPA Axis  depression  fetal programming  polygenic risk Index. décimale : PER Périodiques Résumé : Maternal stress during pregnancy can cause alterations to the fetal hypothalamus-pituitary-adrenal (HPA) axis, a phenomenon known as fetal programming that may have lasting effects on offspring outcomes, including depression. Evidence suggests that these effects may vary with respect to the offspring's genetic risk. Nonetheless, few studies have examined these effects into adulthood, when risk for depression onset is highest. The present study builds upon the extant literature by examining the interaction of maternal prenatal perceived stress (MPPS) and offspring HPA-axis polygenic risk to predict offspring depression in early adulthood. A total of 381 mother-child dyads participated in a prospective, longitudinal study that spanned from pregnancy until offspring were 20 years of age. Polygenic risk was defined by a multilocus genetic profile score (MGPS) that reflected the additive risk of three HPA-axis candidate genes. The results indicated that the interaction of MPPS and HPA-axis MGPS confers risk for offspring depression at age 20, in line with the differential susceptibility model. This interaction may be specific to prenatal stress, as maternal stress during early childhood did not interact with genetic risk to predict depression. These findings provide the first evidence that genetic variants that are associated with the HPA axis may act in a polygenic, additive fashion to moderate the association between fetal programming and adult depression. En ligne : http://dx.doi.org/10.1017/s0954579419001639 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Infant epigenetic aging moderates the link between Black maternal childhood trauma and offspring symptoms of psychopathology / Brooke G. MCKENNA in Development and Psychopathology, 36-4 (October 2024)  

Public ISBD [article]  inDevelopment and Psychopathology > 36-4 (October 2024) . - p.1890-1902 Titre : Infant epigenetic aging moderates the link between Black maternal childhood trauma and offspring symptoms of psychopathology Type de document : texte imprimé Auteurs : Brooke G. MCKENNA, Auteur ; Anna K. KNIGHT, Auteur ; Alicia K. SMITH, Auteur ; Elizabeth J. CORWIN, Auteur ; Sierra E. CARTER, Auteur ; Rohan H.C. PALMER, Auteur ; Anne L. DUNLOP, Auteur ; Patricia A. BRENNAN, Auteur Article en page(s) : p.1890-1902 Langues : Anglais (eng) Mots-clés : child psychopathology  epigenetic aging  intergenerational  trauma Index. décimale : PER Périodiques Résumé : Although offspring of women exposed to childhood trauma exhibit elevated rates of psychopathology, many children demonstrate resilience to these intergenerational impacts. Among the variety of factors that likely contribute to resilience, epigenetic processes have been suggested to play an important role. The current study used a prospective design to test the novel hypothesis that offspring epigenetic aging - a measure of methylation differences that are associated with infant health outcomes - moderates the relationship between maternal exposure to childhood adversity and offspring symptomatology. Maternal childhood adversity was self-reported during pregnancy via the ACEs survey and the CTQ, which assessed total childhood trauma as well as maltreatment subtypes (i.e., emotional, physical, and sexual abuse). Offspring blood samples were collected at or shortly after birth and assayed on a DNA methylation microarray, and offspring symptomatology was assessed with the CBCL/1.5-5 when offspring were 2-4 years old. Results indicated that maternal childhood trauma, particularly sexual abuse, was predictive of offspring symptoms (ps = 0.003-0.03). However, the associations between maternal sexual abuse and offspring symptomatology were significantly attenuated in offspring with accelerated epigenetic aging. These findings further our understanding of how epigenetic processes may contribute to and attenuate the intergenerational link between stress and psychopathology. En ligne : https://dx.doi.org/10.1017/S0954579423001232 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=539 [article] Infant epigenetic aging moderates the link between Black maternal childhood trauma and offspring symptoms of psychopathology [texte imprimé] / Brooke G. MCKENNA, Auteur ; Anna K. KNIGHT, Auteur ; Alicia K. SMITH, Auteur ; Elizabeth J. CORWIN, Auteur ; Sierra E. CARTER, Auteur ; Rohan H.C. PALMER, Auteur ; Anne L. DUNLOP, Auteur ; Patricia A. BRENNAN, Auteur . - p.1890-1902. Langues : Anglais (eng) in Development and Psychopathology > 36-4 (October 2024) . - p.1890-1902 Mots-clés : child psychopathology  epigenetic aging  intergenerational  trauma Index. décimale : PER Périodiques Résumé : Although offspring of women exposed to childhood trauma exhibit elevated rates of psychopathology, many children demonstrate resilience to these intergenerational impacts. Among the variety of factors that likely contribute to resilience, epigenetic processes have been suggested to play an important role. The current study used a prospective design to test the novel hypothesis that offspring epigenetic aging - a measure of methylation differences that are associated with infant health outcomes - moderates the relationship between maternal exposure to childhood adversity and offspring symptomatology. Maternal childhood adversity was self-reported during pregnancy via the ACEs survey and the CTQ, which assessed total childhood trauma as well as maltreatment subtypes (i.e., emotional, physical, and sexual abuse). Offspring blood samples were collected at or shortly after birth and assayed on a DNA methylation microarray, and offspring symptomatology was assessed with the CBCL/1.5-5 when offspring were 2-4 years old. Results indicated that maternal childhood trauma, particularly sexual abuse, was predictive of offspring symptoms (ps = 0.003-0.03). However, the associations between maternal sexual abuse and offspring symptomatology were significantly attenuated in offspring with accelerated epigenetic aging. These findings further our understanding of how epigenetic processes may contribute to and attenuate the intergenerational link between stress and psychopathology. En ligne : https://dx.doi.org/10.1017/S0954579423001232 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=539

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