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BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a prevalent, impairing, and highly heritable condition typically diagnosed in middle childhood. However, it is now recognized that symptoms emerge much earlier in development. Research focused on understanding-using multiple units of analysis-the cascade of early-life (i.e., prenatal-infant-toddler) developmental changes that will later emerge as ADHD has the potential to transform early identification, prevention, and intervention. To this end, we introduce the recently established Early ADHD Consortium, an international network of investigators engaged in prospective, longitudinal studies of risk for ADHD beginning early in life, conducted within a developmental framework, and which incorporate multimethod approaches. This network seeks to harmonize measures and methodological approaches to increase the potential for data sharing and subsequent impact.MethodsThis perspective paper highlights the importance of investigating pre-diagnostic markers of ADHD, and potential models and mechanisms of ADHD risk and development, with the long-term objective of facilitating development of preemptive interventions that will minimize the impact of ADHD symptoms on everyday functioning and maximize health and developmental outcomes.ResultsWe selectively describe key challenges and questions for this field related to theoretical models and developmental mechanisms in ADHD and recommend next steps for the science, including methodological, measurement, and study design considerations. We then describe potential implications for preemptive intervention development. We conclude by considering other issues including ethical concerns and the critical value of incorporating stakeholder input.ConclusionsIt is hoped that this perspective puts forth a research agenda that will enhance collaborative efforts and accelerate progress in understanding developmental mechanisms and the early ADHD phenotype, with implications for early intervention enhancement of healthy development for infants, young children, and their families.

Shared difficulties with cognitive control may play a role in co-occurring mental health problems frequently observed in autistic children. We investigated how different cognitive control processes (inhibitory control, conflict resolution, cognitive flexibility) associated with traits of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) and anxiety in 7-year-old children at elevated (n = 44) and typical (n = 37) familial likelihood for ASD. Poor inhibitory control was associated with higher ADHD traits. Better inhibitory control and poorer cognitive flexibility predicted higher anxiety traits. Cognitive control processes were not associated dimensionally with autistic traits, though better conflict resolution predicted greater likelihood of meeting diagnostic criteria for ASD in categorical analysis. These findings suggest that different cognitive control alterations are associated with ASD, ADHD and anxiety. [This article was co-written with the BASIS Team.]

ObjectiveThe diagnosis of autism spectrum disorder (ASD) has been found to be remarkably stable but few studies have followed children not initially diagnosed with ASD beyond 3 years of age to examine late or delayed diagnoses. The present study used a prospective familial-risk design to identify children who had undergone multiple comprehensive assessments in preschool and were determined to be negative for ASD only to meet criteria for ASD when tested in middle childhood.MethodData were pooled across 3 research teams studying later-born siblings of children with ASD. Fourteen children met inclusion criteria for the late-diagnosed group and were compared with a large sample of high- and low-risk siblings from the same sites who had ASD or typical development (TD) outcomes at 3 years of age.ResultsAs a group, the late-diagnosed children scored between the TD and ASD groups on most measures administered at 3 years and differed significantly from the ASD group on most measures. However, there was significant heterogeneity among the late-diagnosed cases. Seven showed very little evidence of ASD in preschool, whereas 7 demonstrated subtle, subthreshold symptomatology.ConclusionSome children with ASD might present with a subtle phenotype early in life or show a prolonged time course of symptom development. This emphasizes the need for screening and surveillance schedules that extend past 36 months and continued evaluation of any child who presents with atypical early development and/or high-risk status. The findings also shed light on reasons why the mean age of ASD diagnosis remains older than 4 years.

Autism sibling recurrence in prospective infant family history studies is ~20% at 3 years but systematic follow‐up to mid‐childhood is rare. In population and clinical cohorts autism is not recognized in some children until school‐age or later. One hundred and fifty‐nine infants with an older sibling with autism underwent research diagnostic assessments at 3 years and mid‐childhood (6 to 12 years (mean 9)). We report the autism sibling recurrence rate in mid‐childhood and compare developmental and behavioral profiles at mid‐childhood and 3 years in those with earlier versus later recognized autism, and those who had, or had not, received a community autism diagnosis. The autism recurrence rate in this sample in mid‐childhood was 37.1%, 95% CI [29.9%, 44.9%] and higher in boys than girls. Around half of those diagnosed with autism in mid‐childhood had not received a diagnosis at 3 years. Later, diagnosis was more common in girls than boys. While some had sub‐threshold symptoms at 3, in others late diagnosis followed a largely typical early presentation. Sibling recurrence based on community clinical diagnosis was 24.5%, 95% CI [18.4%, 31.9%]. Those who also had a community diagnosis tended to be older, have lower adaptive function and higher autism and inattention symptoms. Notwithstanding limitations of a single site study, modest sample size and limits to generalisability, autism sibling recurrence in family history infants may be higher in mid‐childhood than in studies reporting diagnostic outcome at 3 years. Findings have implications for families and clinical services, and for prospective family history studies. Lay Summary: Autism sibling recurrence in prospective infant family history studies is ~20% at 3 years but follow‐up to mid‐childhood is rare although in some children autism is not recognized until school‐age or later. We assessed 159 infants with an older sibling with autism at 3 years and in mid‐childhood (9 years). The autism sibling recurrence rate in mid‐childhood was 37.1%, 95% CI [29.9%, 44.9%] and higher in boys than girls. Only half of those diagnosed with autism in mid‐childhood had received a diagnosis at 3 years and later diagnosis was more common in girls than boys. Clinicians need provide ongoing monitoring of younger siblings of autism probands to be able to offer support to families when they express concern and seek services. [ABSTRACT FROM AUTHOR]

Shared difficulties with cognitive control may play a role in co-occurring mental health problems frequently observed in autistic children. We investigated how different cognitive control processes (inhibitory control, conflict resolution, cognitive flexibility) associated with traits of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) and anxiety in 7-year-old children at elevated (n = 44) and typical (n = 37) familial likelihood for ASD. Poor inhibitory control was associated with higher ADHD traits. Better inhibitory control and poorer cognitive flexibility predicted higher anxiety traits. Cognitive control processes were not associated dimensionally with autistic traits, though better conflict resolution predicted greater likelihood of meeting diagnostic criteria for ASD in categorical analysis. These findings suggest that different cognitive control alterations are associated with ASD, ADHD and anxiety., Author(s): Priscilla B. G. Godoy [sup.1] , Elizabeth Shephard [sup.1] [sup.2] [sup.5] , Bosiljka Milosavljevic [sup.2] [sup.3] [sup.6] , Mark H. Johnson [sup.3] [sup.4] , Tony Charman [sup.2] , Simon [...]

Cognitive and adaptive behaviour abilities early in life provide important clinical prognostic information. We examined stability of such skills in children at high familial risk for ASD who either met diagnostic criteria for ASD at age 7 years (HR-ASD, n = 15) or did not (HR-non-ASD, n = 24) and low-risk control children (LR, n = 37), prospectively studied from infancy. For both HR groups, cognitive skills were consistently lower across time than those of LR children. HR-ASD children showed increasing difficulties in adaptive behaviour over time compared to LR children, while the HR-non-ASD children showed no such difficulties. This pattern of change may inform our understanding of developmental profiles of HR siblings beyond core ASD symptoms.

Altered power of resting-state neurophysiological activity has been associated with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. We compared resting-state neurophysiological power in children with ASD, ADHD, co-occurring ASD + ADHD, and typically developing controls. Children with ASD (ASD/ASD + ADHD) showed reduced theta and alpha power compared to children without ASD (controls/ADHD). Children with ADHD (ADHD/ASD + ADHD) displayed decreased delta power compared to children without ADHD (ASD/controls). Children with ASD + ADHD largely presented as an additive co-occurrence with deficits of both disorders, although reduced theta compared to ADHD-only and reduced delta compared to controls suggested some unique markers. Identifying specific neurophysiological profiles in ASD and ADHD may assist in characterising more homogeneous subgroups to inform treatment approaches and aetiological investigations.

Anxiety and threat bias were examined in 6-8-year-old children at familial-risk for Autism Spectrum Disorder (ASD) and low-risk (LR, n = 37) controls. The high-risk (HR) group was divided into those who met diagnostic criteria for ASD (HR-ASD, n = 15) and those who did not (HR-non ASD, n = 24). The HR-ASD group had highest levels of parent-reported anxiety. The HR-non ASD group exhibited increased threat bias on a spatial-cueing task, while the HR-ASD group did not. Anxiety symptoms were associated with both threat bias and ASD severity. These findings suggest that the mechanisms underlying anxiety in HR siblings without ASD are similar to those in non-ASD populations. However, among children with ASD, hypersensitivity to threat may not underlie anxiety symptoms. [This report was written with the BASIS Team.]

Effective support for autistic individuals is lacking in Brazil. Few centres offer services and those that do are limited in therapeutic options and geographical location. Paediatric Autism Communication Therapy is a low-intensity, evidence-based parent-mediated social-communication intervention that may be useful for this scenario. This implementation study aimed to assess the acceptability and feasibility of Paediatric Autism Communication Therapy for young autistic children (aged 2–10 years) in Brazil. Parents (n = 18) of 2- to 10-year-old autistic children and clinicians (n = 20) who work with autistic children in Brazil were interviewed and the data analysed using thematic analysis to explore their perceptions concerning the acceptability and feasibility of Paediatric Autism Communication Therapy. In addition, Paediatric Autism Communication Therapy was delivered to a case series of 15 further parent–child dyads; these parents were interviewed at the end of the therapy, and the data were analysed using thematic analysis. All parents and clinicians had favourable opinions about the acceptability, feasibility and perceived effectiveness of a parent-mediated intervention conducted mainly in the home. However, they also highlighted obstacles concerning the implementation of Paediatric Autism Communication Therapy in Brazil, especially related to engaging Brazilian parents in a parent-mediated model of therapy. Based on these data, minor adaptations were made to the original Paediatric Autism Communication Therapy protocol to facilitate the implementation of the intervention in Brazil. Parents of autistic children and health professionals who work with autistic children in Brazil had positive views about introducing Paediatric Autism Communication Therapy as a therapy for autistic children in Brazil. The parents and clinicians also mentioned some difficulties about using Paediatric Autism Communication Therapy in Brazil. We made adaptations to Paediatric Autism Communication Therapy to address these difficulties. Paediatric Autism Communication Therapy is a therapy to support the development of social and communication skills for autistic children aged 2–10 years. The therapy is conducted with the autistic child's parent. Paediatric Autism Communication Therapy has not been used in Brazil before. There are few therapy options available for autistic children in Brazil and we believed that Paediatric Autism Communication Therapy may be useful. We asked three groups of people in Brazil about their views of Paediatric Autism Communication Therapy, after explaining how the therapy works. Group 1 included 18 parents of autistic children aged 2–10 years. Group 2 included 20 health professionals such as psychologists who work with autistic children. Group 3 included 15 parents of autistic children aged 2–7 years who received the Paediatric Autism Communication Therapy. We learned that parents and clinicians felt that Paediatric Autism Communication Therapy would be a beneficial therapy for autistic children in Brazil. We also found out about the challenges of using Paediatric Autism Communication Therapy in Brazil. We used these findings to make small cultural adaptations to Paediatric Autism Communication Therapy to make it more suitable for Brazil. [ABSTRACT FROM AUTHOR]

Cognitive and adaptive behaviour abilities early in life provide important clinical prognostic information. We examined stability of such skills in children at high familial risk for ASD who either met diagnostic criteria for ASD at age 7 years (HR-ASD, n = 15) or did not (HR-non-ASD, n = 24) and low-risk control children (LR, n = 37), prospectively studied from infancy. For both HR groups, cognitive skills were consistently lower across time than those of LR children. HR-ASD children showed increasing difficulties in adaptive behaviour over time compared to LR children, while the HR-non-ASD children showed no such difficulties. This pattern of change may inform our understanding of developmental profiles of HR siblings beyond core ASD symptoms., Author(s): Erica Salomone [sup.1] [sup.2] , Elizabeth Shephard [sup.2] , Bosiljka Milosavljevic [sup.2] , Mark H. Johnson [sup.3] [sup.4] , Tony Charman [sup.2] Author Affiliations: (Aff1) 0000 0001 2336 6580, [...]

Background: Self‐injurious thoughts and behaviours (SITBs) have been associated with dysfunction of the Autonomic Nervous System (ANS) in children and young people, suggesting that objective ANS measures may aid assessment of suicide risk, but a systematic synthesis of this literature is currently lacking. Methods: Following a pre‐registered protocol (PROSPERO CRD42022327605), we conducted a systematic search of PubMed, Medline, Embase, PsycINFO, and Web of Science, for empirical studies published until 10th May 2022 that compared indices of ANS functioning in individuals aged 0–25 years with versus without SITBs, or reported continuous associations between ANS measures and SITBs. Study quality was assessed with the Newcastle‐Ottawa Scales. Pooled effect sizes (Hedge's g) were estimated with random‐effects meta‐analytic models. Results: Twenty studies (1979 participants) were included in our systematic review, with 16 included in meta‐analyses. Results suggested that SITBs were associated with altered cardiac indices of arousal (g = −0.328, p < 0.001), which was driven by lower heart rate variability in individuals with SITBs (g = −0.375, p = 0.025). Overall results for electrodermal activity were not significant (g = 0.026, p = 0.857), but subgroup analyses showed increased activity in studies of individuals who engaged specifically in non‐suicidal self‐harm (g = 0.249, p = 0.014) but decreased activity in the remaining studies (g = −0.567, p = 0.004). Conclusions: Our systematic review and meta‐analysis found evidence of reduced parasympathetic regulation as well as more tentative evidence of altered electrodermal activity in children and young people displaying SITBs. Future longitudinal studies should test the clinical utility of these markers for detecting and monitoring suicide risk. [ABSTRACT FROM AUTHOR]

Altered power of resting-state neurophysiological activity has been associated with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. We compared resting-state neurophysiological power in children with ASD, ADHD, co-occurring ASD + ADHD, and typically developing controls. Children with ASD (ASD/ASD + ADHD) showed reduced theta and alpha power compared to children without ASD (controls/ADHD). Children with ADHD (ADHD/ASD + ADHD) displayed decreased delta power compared to children without ADHD (ASD/controls). Children with ASD + ADHD largely presented as an additive co-occurrence with deficits of both disorders, although reduced theta compared to ADHD-only and reduced delta compared to controls suggested some unique markers. Identifying specific neurophysiological profiles in ASD and ADHD may assist in characterising more homogeneous subgroups to inform treatment approaches and aetiological investigations., Author(s): Elizabeth Shephard [sup.1] [sup.2] , Charlotte Tye [sup.1] [sup.2] , Karen L. Ashwood [sup.3] , Bahar Azadi [sup.2] , Philip Asherson [sup.1] , Patrick F. Bolton [sup.1] [sup.2] , [...]

Anxiety and threat bias were examined in 6-8-year-old children at familial-risk for Autism Spectrum Disorder (ASD) and low-risk (LR, n = 37) controls. The high-risk (HR) group was divided into those who met diagnostic criteria for ASD (HR-ASD, n = 15) and those who did not (HR-non ASD, n = 24). The HR-ASD group had highest levels of parent-reported anxiety. The HR-non ASD group exhibited increased threat bias on a spatial-cueing task, while the HR-ASD group did not. Anxiety symptoms were associated with both threat bias and ASD severity. These findings suggest that the mechanisms underlying anxiety in HR siblings without ASD are similar to those in non-ASD populations. However, among children with ASD, hypersensitivity to threat may not underlie anxiety symptoms., Author(s): Bosiljka Milosavljevic [sup.1] , Elizabeth Shephard [sup.2] , Francesca G. Happé [sup.2] , Mark H. Johnson [sup.3] , Tony Charman [sup.1] Author Affiliations: (1) Department of Psychology, Institute of [...]

The seafood industry in Florida is complex, with more than 80 varieties of Florida seafood commodities and an increasing number of imported products. This variety increases consumer confusion, especially with the growing concern about the origin, sustainability, and safety of seafood products. The objective of the Florida Seafood At Your Fingertips program is to provide Florida Extension agents with updated, science-based information regarding seafood, which will result in increased consumer awareness and consumption. Combining a survey instrument, curriculum modules, public displays, and a mobile application with the teaching expertise of Extension has allowed this program to reach consumers throughout Florida.

Flavin-containing monooxygenase 5 (FMO5) is a member of the FMO family of proteins, best known for their roles in the detoxification of foreign chemicals and, more recently, in endogenous metabolism. We have previously shown that Fmo5-/- mice display an age-related lean phenotype, with much reduced weight gain from 20 weeks of age. The phenotype is characterized by decreased fat deposition, lower plasma concentrations of glucose, insulin and cholesterol, higher glucose tolerance and insulin sensitivity, and resistance to diet-induced obesity. In the present study we report the use of metabolomic and transcriptomic analyses of livers of Fmo5-/- and wild-type mice to identify factors underlying the lean phenotype of Fmo5-/- mice and gain insights into the function of FMO5. Metabolomics was performed by the Metabolon platform, utilising ultrahigh performance liquid chromatography-tandem mass spectroscopy. Transcriptomics was performed by RNA-Seq and results analysed by DESeq2. Disruption of the Fmo5 gene has wide-ranging effects on the abundance of metabolites and expression of genes in the liver. Metabolites whose concentration differed between Fmo5-/- and wild-type mice include several saturated and monounsaturated fatty acids, complex lipids, amino acids, one-carbon intermediates and ADP-ribose. Among the genes most significantly and/or highly differentially expressed are Apoa4, Cd36, Fitm1, Hspa5, Hyou1, Ide, Me1 and Mme. The results reveal that FMO5 is involved in upregulating the NRF2-mediated oxidative stress response, the unfolded protein response and response to hypoxia and cellular stress, indicating a role for the enzyme in adaptation to oxidative and metabolic stress. FMO5 also plays a role in stimulating a wide range of metabolic pathways and processes, particularly ones involved in lipid homeostasis, the uptake and metabolism of glucose, the generation of cytosolic NADPH, and in one-carbon metabolism. The results predict that FMO5 acts by stimulating the NRF2, XBP1, PPARA and PPARG regulatory pathways, while inhibiting STAT1 and IRF7 pathways. [ABSTRACT FROM AUTHOR]

TS school starters had enhanced receptive and expressive language on standardised assessment (CELF-P) and enhanced rhyme judgements, spoonerisms, and lexical decision, indicating enhanced phonological skills and word representations. There was marginal but consistent advantage across lexico-semantic tasks. On executive tasks, speeded naming of numbers was impaired but not pictures. Young TS adults had enhanced naming and receptive vocabulary, indicating enhanced semantic skills. There were consistent deficits in executive language: phonemic oral fluency, rhyme fluency, speeded naming of pictures, numbers and colours; sentence completion requiring supression of prepotent responses. Haploinsufficiency of X-chromosome drives mechanisms that affect the anatomical and neurochemical development of the brain, resulting in enhanced temporal lobe aspects of language. These strengths co-exist with impaired development of frontal lobe executive language systems. This means not only that these elements of language can decouple in development but that their very independence is driven by mechanisms linked to the X-chromosome. (Contains 11 tables.)