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Associations Between Social Responsiveness and Sleep Disruption are Modulated by Chronotype in Early Adolescence: Cross-Sectional and Prospective Findings from 10,108 Participants of the Adolescent Brain and Cognitive Development (ABCD) Study

Background: Sleep disruption is prevalent in people with neurodevelopmental disorders such as autism but is not clear whether it occurs as an endophenotype or secondary to other behaviours. The ABCD Study is a population-based longitudinal study that monitors the health, demography and lifestyle of over 11,000 children in the US. In this study we leverage these data to investigate whether traits consistent with autism (social responsiveness) are associated with sleep disruption independent of lifestyle and other behavioural measures. Methods: Autistic traits were assessed using the Social Responsiveness Scale at age 11, and sleep disruption and behavioural outcomes were assessed at ages 11 and 13 years using the Sleep Disturbance Scale, and the Child Behaviour Check List, respectively. Demographic, health and lifestyle-related variables were assessed by caregiver questionnaires. Regression models were applied to investigate associations between autistic traits and sleep outcomes. Results: There was a significant cross-sectional association between sleep disturbance and SRS at age 11 years old that was independent of sex, ethnicity, socioeconomic position, physical activity, sedentary behaviour and anxiety/depression ({beta} = 0.12, 95% CI (0.07, 0.17); p < 0.001), that persisted at age 13, and that was modulated by chronotype, with evening types showing a stronger association. Discussion: Social responsiveness assessed in early adolescence (age 11) were associated with sleep disruption independent of multiple confounding factors and were prospectively associated with sleep disruption at age 13 years. These findings contribute to the evidence that disruption of sleep and circadian timing may have a primary role in the neurobiological mechanisms that mediate autistic traits.

Sex-specific multimorbidity clusters and all-cause mortality in relatively healthy older adults: findings from the ASPREE cohort

Background: Multimorbidity is common in older adults, but sex differences in chronic condition clustering remain unclear. This study explored multimorbidity clusters and their associations with all-cause mortality among community-dwelling adults aged 70 years and over. Methods: This was a secondary analysis of data from 16,095 Australian ASPREE participants aged at least 70 years without prior dementia or cardiovascular disease. Fifteen baseline chronic conditions were grouped using latent class analysis (LCA). Observed-to-expected (O/E) ratios characterised conditions over-represented within clusters, and Cox proportional hazards models assessed associations with all-cause mortality. Results: Among 16,095 participants (mean age 74 years), 88.3% had multimorbidity at baseline; 4,217 deaths occurred over a median follow-up of 10.85 years. Five clusters were identified overall: hypertension and dyslipidemia (52.1%), gout and metabolic (14.4%), depressive symptoms, osteoporosis and frailty (10.0%), anaemia and kidney disease (10.2%), and hypotension, thyroid disorder and past cancer (13.3%). Sex-stratified analyses revealed three clusters in males and four in females. The frailty, depressive symptoms and osteoporosis cluster was associated with higher mortality in both sexes (aHR 1.56 [95% CI 1.40-1.73] in males; 1.68 [1.49-1.89] in females). Higher mortality was also observed for the metabolic, gout and kidney disease cluster in males (aHR 1.63 [1.47-1.81]) and the gout, anaemia and kidney disease cluster in females (aHR 1.96 [1.74-2.21]). Conclusions: Distinct multimorbidity clusters differed by sex and were associated with increased all-cause mortality. These findings may support risk stratification, targeted screening, and more person-centred management of older adults with multimorbidity.