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The focus of mental health research in emerging fields should be driven by the priorities of people with relevant lived experience. Autism and ADHD are childhood-onset neurodevelopmental conditions that are associated with a range of health inequalities, including increased risk for eating disorders. The evidence base for how best to support neurodivergent individuals who experience disordered eating is still in its infancy, but research suggests that existing clinical approaches are not currently fit for purpose. In this Personal View, through community consultation with autistic people and people with ADHD who have experienced disordered eating, we present a comprehensive ranked list of research topics that people with lived experience prioritise. These priorities could be clustered into two areas: improving outcomes and identifying causal mechanisms. Within the theme of improving disordered eating outcomes, priorities are the improvement of treatment, the need for neurodiversity training in clinical services, and the identification and minimisation of unintended adverse effects of psychological intervention. Within the theme of identifying causal mechanisms, priorities are the identification of risk factors and a better understanding of the effect of autistic or ADHD neurocognitive profiles as potential contributors to eating disorder vulnerability. The final top ten research priorities are contextualised in terms of how they compare to the existing literature on the overlap between autism or ADHD and eating disorders, and concrete suggestions are made for how to implement these research priorities as testable hypotheses. Research informed by these priorities will build necessary understanding of the reasons behind the increased risk for eating disorders in neurodivergent people, and how to best support people who are affected by disordered eating to live positive and fulfilling lives., Competing Interests: Declaration of interests MH has received funding from the Brain and Behaviour Research Foundation, Medical Research Foundation, and MQ. WM has received funding from Autistica, the National Institute of Health and Research (NIHR), the Economic and Social Research Council, the European Research Council, the Medical Research Council, and the Dunhill Medical Trust. He receives small royalties from a cowritten book on helping autistic children transition from primary to secondary school and honoraria for talks to practitioners in the UK, Denmark, and the USA. He also receives payment for legal aid autism assessments for the Just For Kids Law firm, who specialise in working with disadvantaged youth. WM was the chair of the data monitoring and ethics committee for the NIHR-funded REACH-ASD study and chair of the steering committee for the Nuffield Foundation-funded PASTI pilot feasibility trial. VCL has received funding from the Wellcome Trust and King's College London internal MHaPs Early Career Researcher Call grant scheme and is co-chair of the International Society for Autism Research Early Career Committee. JK declares no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Measures of early neuro-cognitive development that are suitable for use in low-resource settings are needed to enable studies of the effects of early adversity on the developing brain in a global context. These measures should have high acquisition rates and good face and construct validity. Here, we investigated the feasibility of a naturalistic electroencephalography (EEG) paradigm in a low-resource context during childhood. Additionally, we examined the sensitivity of periodic and aperiodic EEG metrics to social and non-social stimuli. We recorded simultaneous 20-channel EEG and eye-tracking in 72 children aged 4-12 years (45 females) while they watched videos of women singing nursery rhymes and moving toys, selected to represent familiar childhood experiences. These measures were part of a feasibility study that assessed the feasibility and acceptability of a follow-up data collection of the South African Safe Passage Study, which tracks environmental adversity and brain and cognitive development from before birth up until childhood. We examined whether data quantity and quality varied with child characteristics and the sensitivity of varying EEG metrics (canonical band power in the theta and alpha band and periodic and aperiodic features of the power spectra). We found that children who completed the EEG and eye-tracking assessment were, in general, representative of the full cohort. Data quantity was higher in children with greater visual attention to the stimuli. Out of the tested EEG metrics, periodic measures in the theta frequency range were most sensitive to condition differences, compared to alpha range measures and canonical and aperiodic EEG measures. Our results show that measuring EEG during ecologically valid social and non-social stimuli is feasible in low-resource settings, is feasible for most children, and produces robust indices of social brain function. This work provides preliminary support for testing longitudinal links between social brain function, environmental factors, and emerging behaviors., (© 2024 The Authors. Developmental Psychobiology published by Wiley Periodicals LLC.)

Autistic people experience high rates of co-occurring psychiatric diagnoses. Current prevalence estimates vary considerably due to an over-reliance on clinical cohorts and the longitudinal stability of diagnoses from childhood into adolescence is poorly understood. This study aims to provide prevalence rates of co-occurring DSM-5 psychiatric diagnosis for autistic adolescence and investigate, for the first time, the stability of diagnoses from childhood. Using a longitudinal stratified sample of autistic youth (N = 77; 13-17 years; 60% male), selected from a larger community-derived sample of those with pre-existing autism diagnoses (N = 277) weighted prevalence estimates of emotional (anxiety, depression), behavioural (oppositional and conduct disorders) and ADHD diagnoses were calculated based on semi-structured psychiatric interview. Prediction of adolescent psychiatric diagnosis based on childhood diagnostic status, sex, childhood IQ (both assessed at age 4-10 years) was tested. Emotional and behavioural disorders in adolescence were particularly prevalent, and significantly predicted by childhood disorder status. Attention-deficit/hyperactivity-disorder (ADHD) was prevalent but not predicted by childhood ADHD diagnosis. Neither sex nor childhood IQ predicted diagnostic outcomes. Autistic youth have high levels of co-occurring psychiatric conditions, which are broadly persistent across childhood and adolescence. Emotional disorders are particularly prevalent and remain persistent from childhood to adolescence. Greater diagnostic variability was found for ADHD with more adolescents moving across diagnostic thresholds., (© 2022. The Author(s).)

Neurodevelopmental disorders - including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disability, motor disorders, specific learning disorders, and tic disorders - manifest themselves early in development. Valid, reliable and broadly usable biomarkers supporting a timely diagnosis of these disorders would be highly relevant from a clinical and public health standpoint. We conducted the first systematic review of studies on candidate diagnostic biomarkers for these disorders in children and adolescents. We searched Medline and Embase + Embase Classic with terms relating to biomarkers until April 6, 2022, and conducted additional targeted searches for genome-wide association studies (GWAS) and neuroimaging or neurophysiological studies carried out by international consortia. We considered a candidate biomarker as promising if it was reported in at least two independent studies providing evidence of sensitivity and specificity of at least 80%. After screening 10,625 references, we retained 780 studies (374 biochemical, 203 neuroimaging, 133 neurophysiological and 65 neuropsychological studies, and five GWAS), including a total of approximately 120,000 cases and 176,000 controls. While the majority of the studies focused simply on associations, we could not find any biomarker for which there was evidence - from two or more studies from independent research groups, with results going into the same direction - of specificity and sensitivity of at least 80%. Other important metrics to assess the validity of a candidate biomarker, such as positive predictive value and negative predictive value, were infrequently reported. Limitations of the currently available studies include mostly small sample size, heterogeneous approaches and candidate biomarker targets, undue focus on single instead of joint biomarker signatures, and incomplete accounting for potential confounding factors. Future multivariable and multi-level approaches may be best suited to find valid candidate biomarkers, which will then need to be validated in external, independent samples and then, importantly, tested in terms of feasibility and cost-effectiveness, before they can be implemented in daily clinical practice., (© 2023 World Psychiatric Association.)

Background: The odds ratio (OR) comparing pathogen presence in diarrhoeal cases versus asymptomatic controls is a measure for diarrhoeal disease cause that has been integrated into burden of disease estimates across diverse populations. This study aimed to estimate the OR describing the association between pathogen detection in stool and diarrhoea for 15 common enteropathogens by age group and child mortality setting., Methods: We did a systematic review to identify case-control and cohort studies published from Jan 1, 1990, to July 9, 2019, which examined at least one enteropathogen of interest and the outcome diarrhoea. The analytical dataset included data extracted from published articles and supplemented with data from the Global Enteric Multicenter Study and the Malnutrition and Enteric Disease study. Random effects meta-analysis models were fit for each enteropathogen, stratified by age group and child mortality level, and adjusted for pathogen detection method and study design to produce summary ORs describing the association between pathogen detection in stool and diarrhoea., Findings: 1964 records were screened and 130 studies (over 88 079 cases or diarrhoea samples and 135 755 controls or non-diarrhoea samples) were available for analysis. Heterogeneity (I 2 ) in unadjusted models was substantial, ranging from 27·6% to 86·6% across pathogens. In stratified and adjusted models, summary ORs varied by age group and setting, ranging from 0·4 (95% CI 0·2-0·6) for Giardia lamblia to 54·1 (95% CI 7·4-393·5) for Vibrio cholerae., Interpretation: Incorporating effect estimates from diverse data sources into diarrhoeal disease cause and burden of disease models is needed to produce more representative estimates., Funding: WHO, Bill & Melinda Gates Foundation, and National Institutes of Health., Competing Interests: Declaration of interests VEP has received reimbursement from Merck and Pfizer for travel expenses unrelated to the topic of this Article, and is a member of the WHO Immunization and Vaccine-related Implementation Research Advisory Committee. BAL reports grants and personal fees from Takeda Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2021 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Despite standardized postoperative care, some lung transplant patients suffer multiple episodes of acute and chronic rejection while others avoid graft problems for reasons that are poorly understood. Using an established model of C57BL/10 to C57BL/6 minor antigen mismatched single lung transplantation, we now demonstrate that the recipient microbiota contributes to variability in the alloimmune response. Specifically, mice from the Envigo facility in Frederick, Maryland contain nearly double the number of CD4 + Foxp3 + regulatory T cells (T regs ) than mice from the Jackson facility in Bar Harbor, Maine or the Envigo facility in Indianapolis, Indiana (18 vs 9 vs 7%). Lung graft recipients from the Maryland facility thus do not develop acute or chronic rejection. Treatment with broad-spectrum antibiotics decreases T regs and increases both acute and chronic graft rejection in otherwise tolerant strains of mice. Constitutive depletion of regulatory T cells, using Foxp3-driven expression of diphtheria toxin receptor, leads to the development of chronic rejection and supports the role of T regs in both acute and chronic alloimmunity. Taken together, our data demonstrate that the microbiota of certain individuals may contribute to tolerance through T reg -dependent mechanisms and challenges the practice of indiscriminate broad-spectrum antibiotic use in the perioperative period., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: Asthma and allergic diseases continue to increase in prevalence, creating a financial burden on the health care system and affecting the quality of life for those who have these diseases. Many intrinsic and extrinsic factors are involved in the initiation and maintenance of the allergic response. Cytokines are proteins with growth, differentiation, and activation functions that regulate and direct the nature of immune responses., Data Sources: clinicaltrials.gov and PubMed., Study Selections: Relevant clinical trials and recent basic science studies were chosen for discussion., Results: Many cytokines have been implicated in the development and perpetuation of the allergic response. Biologics have been and are continuing to be developed that target these molecules for use in patients with asthma and atopic dermatitis where standard treatment options fail. The current state of cytokine-targeting therapies is discussed., Conclusion: This review focused on cytokines involved in the allergic response with an emphasis on those for which therapies are being or have been developed., (Copyright © 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: To discuss the general immunologic changes that occur during immunotherapy, focusing on the differences between subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT)., Data Sources: PubMed literature review., Study Selections: Articles pertaining to SCIT and SLIT, with specific emphasis on those that included immune mechanistic studies., Results: Both SCIT and SLIT are characterized by the induction of regulatory B and T cells, decreased allergen-specific T-cell proliferation, a shift from a TH2 to TH1 cytokine milieu and from an IgE to an IgG4/IgA antibody response. These changes are accompanied by clinical improvement in symptoms., Conclusion: Immunotherapy using allergen extracts administered via both subcutaneous and sublingual approaches have demonstrated efficacy in the treatment of allergic rhinoconjunctivitis and other allergic conditions. There are subtle differences between the approaches, and understanding these differences may help clinicians select a preferred route of therapy for particular patients or allergens, depending on the immune response that is being targeted., (Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: People with callous-unemotional traits and also those with autism spectrum disorder (ASD) display sociocognitive difficulties. However, the frequency and neurocognitive correlates of callous-unemotional traits within individuals with ASD are unknown., Aims: To determine the prevalence of callous-unemotional traits in individuals with ASD and test their association with behavioural and cognitive measures., Method: Parents of 92 adolescents with ASD completed the Antisocial Processes Screening Device (APSD) for callous-unemotional traits. Adolescents participated in tasks of emotion recognition, theory of mind and cognitive flexibility., Results: In total 51% (n = 47) scored above a cut-off expected to identify the top 6% on the APSD. Of these 17% (n = 8) had concurrent conduct problems. Regression analyses found callous-unemotional traits were associated with specific impairment in fear recognition but not with theory of mind or cognitive flexibility., Conclusions: Adolescents with ASD show high rates of callous-unemotional traits but, unlike in the general population, these are not strongly associated with conduct problems. The relationship of callous-unemotional traits to impairments in fear recognition suggests similar affective difficulties as in individuals with callous-unemotional traits without ASD., (© The Royal College of Psychiatrists 2015.)

Background: Intestinal mucositis is one of the major troublesome side effects of anticancer chemotherapy leading to poor patient compliance. In this study we addressed the role of the novel apolipoprotein E (ApoE) COG 133 mimetic peptide in 5-fluorouracil (5-FU)-challenged Swiss mice and IEC-6 cell monolayers. Experiments were also conducted in C57BL6J ApoE knock-out mice to assess the effects of apoE peptide treatment., Methods: Experimental groups were as follows: unchallenged controls, 5-FU-challenged mice (450 mg/kg, i.p) with or without the ApoE peptide (0.3, 1, and 3 μM, given twice daily i.p. for 4 days). Mice were sacrificed 3 days after 5-FU challenge. Proximal small intestinal samples were harvested for molecular biology and histological processing. We conducted ELISA assays and RT-PCR to target IL-1β, TNF-α, IL-10, iNOS, and myeloperoxidase (MPO) to assess intestinal inflammation. Cell death and NF-κB assays were also conducted in apoE knock-out mice. In our in vitro models, IEC-6 cells were exposed to 1 mM of 5-FU in glutamine free media with or without the ApoE peptide (0.02, 0.2, 2, 5, 10, and 20 μM). We investigated IEC-6 cell proliferation and migration, 24 h after the 5-FU challenge. Additionally, apoptotic IEC-6 cells were measured by Tunel and flow cytometry. Equimolar doses of the ApoA-I (D4-F) peptide were also used in some experiments for comparative studies., Results: Villus blunting and heavy inflammatory infiltrates were seen in the 5-FU-challenged group, findings that were partially ameliorated by the ApoE peptide. We found increased intestinal MPO and pro-inflammatory IL-1β and TNF-α levels, and TNF-α and iNOS transcripts, and reduction of IL-10 following 5-FU treatment, each of which were partially abrogated by the peptide. Improvements were also found in IEC-6 cell apoptosis and migration following ApoE and D-4F treatment., Conclusion: Altogether, these findings suggest that the novel ApoE COG 133 mimetic peptide can reduce 5-FU-induced intestinal changes and potentially benefit mucositis.