1. Bhat SS, Kalal BS, Veena KM, Kakunje A, Sahana KSR, Rekha PD, Chandra J, Nasreen I. Serum and salivary immunoglobulin G4 levels in children with autism spectrum disorder from south India: a case-control study. American journal of clinical and experimental immunology. 2021; 10(4): 103-11.

BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with wide spectrum of symptoms and few effective therapies. Evidence is suggestive of an association between immune system dysfunction and autism spectrum disorders (ASD) among children with ASD. Immunoglobulins (Ig) are found to be increased in the circulation of individuals with autism. The prospective study was aimed to estimate and correlate the levels of IgG4 in blood and saliva of children with autism. METHODOLOGY: Blood and unstimulated saliva were collected from 172 children (55 ASD, 57 healthy control, and 60 suspected parasitic infection) aged 0-18 years. Routine blood investigations were done. Serum and salivary IgG4 levels were analyzed using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Data were subjected to statistical analysis. RESULTS: ELISA tests showed that the IgG4 levels in serum and saliva were significantly increased (P<0.05) in children with ASD as compared to normal control children. Both serum and saliva IgG4 levels showed a significant positive correlation (P<0.05). CONCLUSION: IgG4 can be used as a potential biomarker for the early detection of ASD. Further, saliva can be a diagnostic, noninvasive assessment tool for health monitoring of children with autism. Lay summary: The collection of saliva is easy and painless compared to other sample collection methods. The present study shows that, among children with autism, brain-reactive antibody, immunoglobulin G4 (gG4), is increased both in blood and saliva, and there is a significant correlation between the two levels. Therefore, the study recommends IgG4 as a potential biomarker for the early detection of autism, and saliva can be helpful in diagnosis and health monitoring of children with ASD.

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2. Bradley CB, Tapia AL, DiGuiseppi CG, Kepner MW, Kloetzer JM, Schieve LA, Wiggins LD, Windham GC, Daniels JL. Reasons for participation in a child development study: Are cases with developmental diagnoses different from controls?. Paediatric and perinatal epidemiology. 2022; 36(3): 435-45.

BACKGROUND: Current knowledge about parental reasons for allowing child participation in research comes mainly from clinical trials. Fewer data exist on parents’ motivations to enrol children in observational studies. OBJECTIVES: Describe reasons parents of preschoolers gave for participating in the Study to Explore Early Development (SEED), a US multi-site study of autism spectrum disorder (ASD) and other developmental delays or disorders (DD), and explore reasons given by child diagnostic and behavioural characteristics at enrolment. METHODS: We included families of children, age 2-5 years, participating in SEED (n = 5696) during 2007-2016. We assigned children to groups based on characteristics at enrolment: previously diagnosed ASD; suspected ASD; non-ASD DD; and population controls (POP). During a study interview, we asked parents their reasons for participating. Two coders independently coded responses and resolved discrepancies via consensus. We fit binary mixed-effects models to evaluate associations of each reason with group and demographics, using POP as reference. RESULTS: Participants gave 1-5 reasons for participation (mean = 1.7, SD = 0.7). Altruism (48.3%), ASD research interest (47.4%) and perceived personal benefit (26.9%) were most common. Two novel reasons were knowing someone outside the household with the study conditions (peripheral relationship; 14.1%) and desire to contribute to a specified result (1.4%). Odds of reporting interest in ASD research were higher among diagnosed ASD participants (odds ratio [OR] 2.89, 95% confidence interval [CI] 2.49-3.35). Perceived personal benefit had higher odds among diagnosed (OR 1.92, 95% CI 1.61-2.29) or suspected ASD (OR 3.67, 95% CI 2.99-4.50) and non-ASD DD (OR 1.80, 95% CI 1.50-2.16) participants. Peripheral relationship with ASD/DD had lower odds among all case groups. CONCLUSIONS: We identified meaningful differences between groups in parent-reported reasons for participation. Differences demonstrate an opportunity for future studies to tailor recruitment materials and increase the perceived benefit for specific prospective participants.

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3. Chen Y, Xueying Z, Jiaqu C, Qiyi C, Huanlong Q, Ning L, Yasong D, Xiaoxin Z, Rong Y, Jubao L, Xiaoqiong L, Chunlian M, Yu W, Shidong C, Guifang K, Dongmei Z, Shuanfeng F, Xujing Z, Binrang Y, Yanxia W, Ling L, Song Y, Xiang Z, Beihua Z, Lin J, Hong J. FTACMT study protocol: a multicentre, double-blind, randomised, placebo-controlled trial of faecal microbiota transplantation for autism spectrum disorder. BMJ open. 2022; 12(1): e051613.

INTRODUCTION: Autism spectrum disorder (ASD) is a complicated diffuse developmental disorder that commonly involves gastrointestinal distress and dysbacteriosis. Emerging lines of evidence have shown faecal microbiota transplantation (FMT) to be a potential therapeutic strategy for improving the clinical outcomes of patients with ASD by re-establishing their intestinal microflora. We are undertaking the first-ever multicentre, double-blind, randomised controlled trial of FMT for the treatment of children with both ASD and gastrointestinal symptoms and will assess the feasibility and efficacy outcomes of this strategy. METHODS: In total, 318 children with both ASD and gastrointestinal symptoms will be enrolled (from 15 hospitals in China) to receive either FMT intervention (n=212) or a placebo (control, n=106). Children aged 3-6 years will take two capsules two times a day, and those older than 6 years will take three capsules two times a day. Each patient will receive four treatment courses, with each 12-day course being repeated every month. Outcomes will be evaluated at baseline, throughout the period of intervention, and at subsequent follow-ups for 2 months. The primary trial objective is to investigate the remodelling effect of FMT on the intestinal microflora in patients with ASD. The secondary objective focuses on the clinical efficacy and safety of FMT, including its improvement of the clinical response and metabonomics. ETHICS AND DISSEMINATION: Ethical approval was obtained from the hospital Ethics Committee of each Faecal Transfer for ASD China Multicenter Trial Working Group. The ongoing FMT clinical trial is intended to support the approval of the new technology and its administration. The results of this trial will provide high-quality evidence to inform the future clinical application of this new therapy. TRIAL REGISTRATION NUMBER: ChiCTR2100043906; Pre-results.

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4. Dell’Osso L, Carpita B. What misdiagnoses do women with autism spectrum disorder receive in the DSM-5?. CNS spectrums. 2022: 1-2.

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5. Elkhatib Smidt SD, Hitt T, Zemel BS, Mitchell JA. Sex differences in childhood sleep and health implications. Annals of human biology. 2021; 48(6): 474-84.

CONTEXT: Sleep is critical for optimal childhood metabolic health and neurodevelopment. However, there is limited knowledge regarding childhood sex differences in sleep, including children with neurodevelopmental disorders, and the impact of such differences on metabolic health. OBJECTIVE: To evaluate if sex differences in childhood sleep exist and if sleep associates with metabolic health outcomes equally by sex. Using autism spectrum disorder (ASD) as a case study, we also examine sleep sex differences in children with a neurodevelopmental disorder. METHODS: A narrative review explored the literature focussing on sex differences in childhood sleep. RESULTS: Sex differences in sleep were not detected among pre-adolescents. However, female adolescents were more likely to report impaired sleep than males. Childhood obesity is more common in males. Shorter sleep duration may be associated with obesity in male pre-adolescents/adolescents; although findings are mixed. ASD is male-predominant; yet, there was an indication that pre-adolescent female children with ASD had more impaired sleep. CONCLUSION: Sex differences in sleep appear to emerge in adolescence with more impaired sleep in females. This trend was also observed among pre-adolescent female children with ASD. Further research is needed on sex differences in childhood sleep and metabolic health and the underlying mechanisms driving these differences.

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6. Hampton S, Allison C, Aydin E, Baron-Cohen S, Holt R. Autistic mothers’ perinatal well-being and parenting styles. Autism : the international journal of research and practice. 2022: 13623613211065544.

Autistic people can have difficulties during pregnancy and after giving birth, such as difficulty getting health care that meets their needs. Autistic people may therefore have lower well-being than non-autistic people during this time. We asked autistic and non-autistic people to fill in questionnaires measuring stress, depression, anxiety and satisfaction with life. They were asked to do this once during pregnancy, once 2 to 3 months after giving birth and once 6 months after giving birth. At 6 months after giving birth, they also filled in questionnaires about parenting. The autistic parents had higher stress, depression and anxiety scores than the non-autistic parents. For both groups, scores for anxiety went down over time. There were no differences between the groups on satisfaction with their life or how confident they were as a parent. There were no differences between the groups on most areas of parenting style, although autistic parents scored lower on parenting discipline. This study suggests that autistic people may be more stressed, depressed and anxious than non-autistic people during pregnancy and after giving birth. Autistic people therefore need good quality support during this time. This study also suggests that autistic and non-autistic parents may be just as likely to parent in positive ways such as being sensitive to their baby’s needs.

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7. Munoz Murakami LY, van der Miesen AIR, Nabbijohn AN, VanderLaan DP. Childhood Gender Variance and the Autism Spectrum: Evidence of an Association Using a Child Behavior Checklist 10-Item Autism Screener. Journal of sex & marital therapy. 2022: 1-7.

Childhood gender variance (GV) is associated with autism spectrum disorder (ASD) diagnosis/traits; however, this association has mainly been investigated in clinical samples. An ASD screening measure based on 10 items from the commonly used Child Behavior Checklist (CBCL) might enable investigation of this association in a wider variety of (non-clinical) populations where the CBCL and a measure of GV are available. We investigated whether GV in 6- to 12-year-olds (N = 1719; 48.8% assigned male at birth) from a community sample showed an association with the CBCL 10-item ASD screener. The Gender Identity Questionnaire for Children measured GV. The CBCL 10-item ASD screener measured ASD traits. The remaining CBCL items provided a measure of children’s general emotional and behavioral challenges. Higher GV was associated with higher CBCL ASD screener scores, including when controlling for the remaining CBCL items. The CBCL 10-item ASD screener can be useful for investigating the link between GV and ASD traits in 6- to 12-year-olds. Given that the CBCL is commonly employed, secondary analyses of existing datasets that also included a measure of GV could enable investigation of how widely the association between GV and ASD applies across a variety of populations.

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8. Nguyen MG, Tronick L, Modirian F, Mardach R, Besterman AD. Neurodevelopmental and neuropsychiatric disorders in cobalamin C disease: a case report and review of the literature. Cold Spring Harbor molecular case studies. 2022; 8(2).

Cobalamin C disease is the most common complementation class of cobalamin disorders. Here, we present a case of a 14-yr-old male with early-onset cblC disease and autism spectrum disorder (ASD) admitted to our inpatient medical service for behavioral decompensation. We use this case to highlight key aspects of the neurodevelopmental and neuropsychiatric disorders associated with cblC disease. By incorporating a comprehensive review of existing literature, we highlight salient domains of psychological impairment in cblC disease, discuss the full range of neuropsychiatric presentations, and review clinical management implications unique to cblC disease.

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9. Özcan E, Hsiao EY. Are changes in the gut microbiome a contributor or consequence of autism-why not both?. Cell reports Medicine. 2022; 3(1): 100505.

Alterations in the gut microbiome have been associated with autism spectrum disorder (ASD), but whether they are a cause, effect, or confounder remains unclear. In a recent issue of Cell, Yap and colleagues report that ASD-associated microbiota changes are likely a consequence of low diet diversity.(1).

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10. Stadnick NA, Martinez K, Coleman KJ, Gizzo DP, Lane E, Lee N, Kuelbs CL, Aarons GA, Brookman-Frazee L. Mental health screening in pediatric primary care for children with autism. Autism : the international journal of research and practice. 2022: 13623613211062963.

Children with autism experience high rates of co-occurring mental health conditions like challenging behaviors and anxiety. However, these co-occurring mental health needs are often not identified when they first become problematic. Pediatricians and their care staff are in a good position to identify mental health needs early and support families to connect to needed services. This study describes a project focused on mental health screening for children with autism in pediatric primary care clinics. Over half of eligible patients were screened using the Pediatric Symptom Checklist-17. Many children with autism had clinically elevated scores, suggesting the need for mental health assessment or services. In particular, children with positive screens had clinical elevations on the challenging behavior and attention subscales of the Pediatric Symptom Checklist-17. This finding is consistent with typical trends in co-occurring challenging behavior presentations in children with autism. Mental health screening in primary care is feasible and offers a promising opportunity to identify co-occurring mental health needs for children with autism early. Screening rates varied between clinics, suggesting tailored to improve routine screening in pediatric primary care for children with autism.

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11. Takai H, Sunagawa Y, Funamoto M, Shimizu K, Shimizu S, Katanasaka Y, Miyazaki Y, Imaizumi A, Hashimoto T, Wada H, Hasegawa K, Morimoto T. A Novel Curcumin Formulation, ASD-Cur, Suppressed the Development of Systolic Dysfunction After Myocardial Infarction in Rats. European cardiology. 2021; 16: e69.

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