Amygdala subnuclei development in adolescents with autism spectrum disorder: Association with social communication and repetitive behaviors

Introduction: The amygdala subnuclei regulate emotional processing and are widely implicated in social cognitive impairments often seen in children with autism spectrum disorder (ASD). Dysregulated amygdala development has been reported in young children with ASD; less is known about amygdala maturation in later adolescence, a sensitive window for social skill development. Methods: The macrostructural development of the amygdala subnuclei was assessed at two time points in a longitudinal magnetic resonance imaging (MRI) study of adolescents with ASD (n = 23) and typically-developing adolescents (n = 15). In adolescents with ASD, amygdala subnuclei growth was assessed in relation to ASD symptomatology based on standardized diagnostic assessments. Participants were scanned with MRI at median age of 12 years and returned for a second scan at a median age of 15 years. The volumes of nine amygdala subnuclei were extracted using an automatic segmentation algorithm. Results: When examining the longitudinal data acquired across two time points, adolescents with ASD had larger basolateral amygdala (BLA) nuclei volumes compared to typically developing adolescents (B = 46.8, p = 0.04). When examining ASD symptomatology in relation to the growth of the amygdala subnuclei, reciprocal social interaction scores on the ADI-R were positively associated with increased growth of the BLA nuclei (B = 8.3, p \u3c 0.001). Growth in the medial nucleus negatively predicted the communication (B = −46.9, p = 0.02) and social (B = −47.7, p \u3c 0.001) domains on the ADOS-G. Growth in the right cortical nucleus (B = 26.14, p = 0.02) positively predicted ADOS-G social scores. Central nucleus maturation (B = 29.9, p = 0.02) was associated with the repetitive behaviors domain on the ADOS-G. Conclusions: Larger BLA volumes in adolescents with ASD may reflect underlying alterations in cellular density previously reported in post-mortem studies. Furthermore, findings demonstrate an association between regional growth in amygdala subnuclei volumes and ASD symptomatology. Improved understanding of the developmental trajectories of the amygdala subnuclei may aid in identifying key windows for interventions, particularly for social communication, in adolescents with ASD

Huella de carbono de los patrones de consumo de la UE desde una perspectiva multirregional: desigualdad y evolución reciente.

La reciente preocupación por las consecuencias presentes y futuras del cambio climático, ha llevado a que diferentes organizaciones internacionales, como el Marco de la Convención de las Naciones Unidas en el Cambio Climático, y especialmente el Acuerdo de París, tengan como objetivo alcanzar un desarrollo sostenible. Estos acuerdos reflejan la preocupación de cómo reducir las emisiones de los gases de efecto invernadero y el requerimiento de organizar a todos los países para conseguir mejoras medio ambientales. En los últimos años, los investigadores han señalado a los hogares como un elemento de gran relevancia en los impactos ambientales. La producción y patrón de consumo en cada país provocan emisiones indirectas a la atmósfera a través de su cadena de producción, siendo un elemento clave en las políticas climáticas y en el camino hacia la sostenibilidad y reducción de emisiones. Las diferencias en la distribución de la renta, así como en los estilos de vida entre los países y dentro de los mismos, suponen un punto de partida diferente para cada país para cumplir sus objetivos.En este contexto, analizamos las implicaciones del carbono en la producción, y especialmente en los patrones de consumo, utilizando un modelo multi-regional y multisectorial input-output para los estados miembros de la UE, considerando 26 sectores. Evaluamos los diferentes patrones de consumo de los hogares entre el 2000 y 2015, utilizando cinco categorías de renta. Además, evaluamos dos posibles escenarios y sus consecuencias i) Un primer escenario con una mayor equidad en la distribución de la renta ii) Un cambio en el patrón de consumo con una reducción del uso de transporte.<br /

Amygdala subnuclei volumes and anxiety behaviors in children and adolescents with autism spectrum disorder, attention deficit hyperactivity disorder, and obsessive–compulsive disorder

Alterations in the structural maturation of the amygdala subnuclei volumes are associated with anxiety behaviors in adults and children with neurodevelopmental and associated disorders. This study investigated the relationship between amygdala subnuclei volumes and anxiety in 233 children and adolescents (mean age = 11.02 years; standard deviation = 3.17) with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and children with obsessive compulsive disorder (OCD), as well as typically developing (TD) children. Parents completed the Child Behavior Checklist (CBCL), and the children underwent structural MRI at 3 T. FreeSurfer software was used to automatically segment the amygdala subnuclei. A general linear model revealed that children and adolescents with ASD, ADHD, and OCD had higher anxiety scores compared to TD children (p \u3c.001). A subsequent interaction analysis revealed that children with ASD (B = 0.09, p \u3c.0001) and children with OCD (B = 0.1, p \u3c.0001) who had high anxiety had larger right central nuclei volumes compared with TD children. Similar results were obtained for the right anterior amygdaloid area. Amygdala subnuclei volumes may be key to identifying children with neurodevelopmental disorders or those with OCD who are at high risk for anxiety. Findings may inform the development of targeted behavioral interventions to address anxiety behaviors and to assess the downstream effects of such interventions

Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome

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Germline MBD4 deficiency causes a multi-tumor predisposition syndrome

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management

Germline MBD4-deficiency causes a multi-tumor predisposition syndrome

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management

Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood : An individual participant data meta-analysis

Background Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. Methods and findings We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestylerelated characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p <0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. Conclusions In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.Peer reviewe

Gestational weight gain charts for different body mass index groups for women in Europe, North America and Oceania

Background: Gestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grade 1, 2 and 3 obese women and compare these charts with those obtained in women with uncomplicated term pregnancies.Methods: We used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America and Oceania. Of these women, 9,065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3,597 (1.6%), and 1,095 (0.5%) were underweight, normal weight, overweight, and grade 1, 2 and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2 and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale and shape. Results: We observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40 weeks was 14.2 kg (11.4-17.4) for underweight women, 14.5 kg (11.5-17.7) for normal weight women, 13.9 kg (10.1-17.9) for overweight women, and 11.2 kg (7.0-15.7), 8.7 kg (4.3-13.4) and 6.3 kg (1.9-11.1) for grade 1, 2 and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications.Conclusions: Gestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice