Determining Relationships among Executive Functioning, Empathy, and Autism Spectrum Disorder Traits in Neurotypical Adults

Previous research has established that individuals with autism spectrum disorder (ASD) often have impairments in both cognitive empathy and executive functioning (EF), although little attention has been devoted to the relationships among these domains and ASD traits. Furthermore, the presence of an emotional empathy deficit in individuals with ASD has only begun to be explored, and studies have yielded discrepant findings likely attributable to differences in methodology and limited consideration of positive versus negative content. There is some evidence to suggest that EF may be important for emotional empathy and ASD traits. The current study aimed to clarify the relationships among these variables by examining the possibility that EF mediates the relationship between empathy and ASD traits in neurotypical adults. Although hypotheses regarding mediation were not supported, the study revealed a novel finding that positive emotional empathy was negatively associated with ASD traits, whereas cognitive empathy was not associated with ASD traits. Furthermore, planning ability was positively associated with cognitive empathy. Implications for future research based on these findings are discussed

Identifying Predictors of Diagnostic Instability of Autism Spectrum Disorder and Global Developmental Delay In Toddlers

Although Autism Spectrum Disorder (ASD) is considered to be a lifelong condition, some toddlers experience diagnostic instability over time. In particular, some toddlers’ diagnosis changes between ASD and Global Developmental Delay (GDD). However, little is known about the subset of children who change diagnosis. In a total of 424 toddlers who either maintained or changed diagnosis, the current study identified predictors of change in diagnosis and severity in those who change from ASD to non-ASD (ASD-NON), ASD to GDD (ASD-GDD), non-ASD to ASD (NON-ASD), and GDD to ASD (GDD-ASD) between two years old and four years old. Initial ASD symptom severity and participation in intervention services were predictive of all transitions. Additionally, receptive language predicted ASD-NON transition and socioeconomic status predicted ASD-GDD transition. Implications for informing prognosis of children, identifying targets of intervention, refining of screening and diagnostic measures, and measuring change in severity regardless of categorical change are discussed

Default mode network segregation and social deficits in autism spectrum disorder: Evidence from non-medicated children DMN in children with ASD

AbstractFunctional pathology of the default mode network is posited to be central to social-cognitive impairment in autism spectrum disorders (ASD). Altered functional connectivity of the default mode network's midline core may be a potential endophenotype for social deficits in ASD. Generalizability from prior studies is limited by inclusion of medicated participants and by methods favoring restricted examination of network function. This study measured resting-state functional connectivity in 22 8–13 year-old non-medicated children with ASD and 22 typically developing controls using seed-based and network segregation functional connectivity methods. Relative to controls the ASD group showed both under- and over-functional connectivity within default mode and non-default mode regions, respectively. ASD symptoms correlated negatively with the connection strength of the default mode midline core—medial prefrontal cortex–posterior cingulate cortex. Network segregation analysis with the participation coefficient showed a higher area under the curve for the ASD group. Our findings demonstrate that the default mode network in ASD shows a pattern of poor segregation with both functional connectivity metrics. This study confirms the potential for the functional connection of the midline core as an endophenotype for social deficits. Poor segregation of the default mode network is consistent with an excitation/inhibition imbalance model of ASD

A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

J. Kaprio, A. Palotie, A. Raevuori-Helkamaa ja S. Ripatti ovat työryhmän Eating Disorders Working Group of the Psychiatric Genomics Consortium jäseniä. Erratum in: Sci Rep. 2017 Aug 21;7(1):8379, doi: 10.1038/s41598-017-06409-3We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 x 10(-7); OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.Peer reviewe

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Motor demands impact speed of information processing in autism spectrum disorders

OBJECTIVE: The apparent contradiction between preserved or even enhanced perceptual processing speed on inspection time tasks in autism spectrum disorders (ASD) and impaired performance on complex processing speed tasks that require motor output (e.g. Wechsler Processing Speed Index) has not yet been systematically investigated. This study investigates whether adding motor output demands to an inspection time task impairs ASD performance compared to that of typically developing control (TDC) children. METHOD: The performance of children with ASD (n=28; mean FSIQ=115) and TDC (n=25; mean FSIQ=122) children was compared on processing speed tasks with increasing motor demand. Correlations were run between ASD task performance and Autism Diagnostic Observation Schedule (ADOS) Communication scores. RESULTS: Performance by the ASD and TDC groups on a simple perceptual processing speed task with minimal motor demand was equivalent, though it diverged (ASD worse than TDC) on two tasks with the same stimuli, but increased motor output demands. ASD performance on the moderate but not the high speeded motor output demand task was negatively correlated with ADOS communication symptoms. CONCLUSIONS: These data address the apparent contradiction between preserved inspection time in the context of slowed “processing speed” in ASD. They show that processing speed is preserved when motor demands are minimized, but that increased motor output demands interfere with the ability to act on perceptual processing of simple stimuli. Reducing motor demands (e.g. through the use of computers) may increase the capacity of people with ASD to demonstrate good perceptual processing in a variety of educational, vocational and social settings

Default mode network segregation and social deficits in autism spectrum disorder: Evidence from non-medicated children

Functional pathology of the default mode network is posited to be central to social-cognitive impairment in autism spectrum disorders (ASD). Altered functional connectivity of the default mode network's midline core may be a potential endophenotype for social deficits in ASD. Generalizability from prior studies is limited by inclusion of medicated participants and by methods favoring restricted examination of network function. This study measured resting-state functional connectivity in 22 8–13 year-old non-medicated children with ASD and 22 typically developing controls using seed-based and network segregation functional connectivity methods. Relative to controls the ASD group showed both under- and over-functional connectivity within default mode and non-default mode regions, respectively. ASD symptoms correlated negatively with the connection strength of the default mode midline core—medial prefrontal cortex–posterior cingulate cortex. Network segregation analysis with the participation coefficient showed a higher area under the curve for the ASD group. Our findings demonstrate that the default mode network in ASD shows a pattern of poor segregation with both functional connectivity metrics. This study confirms the potential for the functional connection of the midline core as an endophenotype for social deficits. Poor segregation of the default mode network is consistent with an excitation/inhibition imbalance model of ASD