1. Blanchard A, Chihuri S, DiGuiseppi CG, Li G. Risk of Self-harm in Children and Adults With Autism Spectrum Disorder: A Systematic Review and Meta-analysis. JAMA network open. 2021; 4(10): e2130272.

IMPORTANCE: Multiple studies have reported that people with autism spectrum disorder (ASD) are at a higher risk for self-injurious behavior and suicide. However, the magnitude of this association varies between studies. OBJECTIVE: To appraise the available epidemiologic studies on the risk of self-injurious behavior and suicidality among children and adults with ASD. DATA SOURCES: PubMed, Embase, CINAHL, PsycINFO, and Web of Science were systematically searched for epidemiologic studies on the association between ASD and self-injurious behavior and suicidality. Databases were searched from year of inception to April through June 2020. No language, age, or date restrictions were applied. STUDY SELECTION: This systematic review and meta-analysis included studies with an observational design and compared self-injurious behavior (defined as nonaccidental behavior resulting in self-inflicted physical injury but without intent of suicide or sexual arousal) and/or suicidality (defined as suicidal ideation, suicide attempt, or suicide) in children (aged <20 years) or adults (aged ≥20 years) with ASD. DATA EXTRACTION AND SYNTHESIS: Information on study design, study population, ASD and self-harm definitions, and outcomes were extracted by independent investigators. Study quality was assessed using the Newcastle-Ottawa Scale. Overall summary odds ratios (ORs) and 95% CIs were estimated using DerSimonian-Laird random-effects models. MAIN OUTCOMES AND MEASURES: The ORs for the associations of ASD with self-injurious behavior and suicidality were calculated. Analyses were stratified by study setting and age groups as planned a priori. RESULTS: The search identified 31 eligible studies, which were of moderate to high quality. Of these studies, 16 (52%) were conducted in children, 13 (42%) in adults, and 2 (6%) in both children and adults. Seventeen studies assessed the association between ASD and self-injurious behavior and reported ORs that ranged from 1.21 to 18.76, resulting in a pooled OR of 3.18 (95% CI, 2.45-4.12). Sixteen studies assessed the association between ASD and suicidality and reported ORs that ranged from 0.86 to 11.10, resulting in a pooled OR of 3.32 (95% CI, 2.60-4.24). In stratified analyses, results were consistent between clinical and nonclinical settings and between children and adults. CONCLUSIONS AND RELEVANCE: This study found that ASD was associated with a substantial increase in odds of self-injurious behavior and suicidality in children and adults. Further research is needed to examine the role of primary care screenings, increased access to preventive mental health services, and lethal means counseling in reducing self-harm in this population.

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2. Costa CIS, da Silva Montenegro EM, Zarrei M, de Sá Moreira E, Silva IMW, de Oliveira Scliar M, Wang JYT, Zachi EC, Branco EV, da Costa SS, Lourenço NCV, Vianna-Morgante AM, Rosenberg C, Krepischi ACV, Scherer SW, Passos-Bueno MR. Copy number variations in a Brazilian cohort with autism spectrum disorders highlight the contribution of cell adhesion genes. Clinical genetics. 2022; 101(1): 134-41.

Prediction of pathogenicity of rare copy number variations (CNVs), a genomic alteration known to contribute to the etiology of autism spectrum disorder (ASD), represents a serious limitation to interpreting genetic tests, particularly for genetic counseling purposes. Chromosomal microarray analysis (CMA) was conducted in a unique collection of 144 Brazilian individuals with ASD of strong European and African ancestries. Rare CNVs were detected in 39 patients: 41 of unknown significance (VUS), four pathogenic and one likely pathogenic CNVs (clinical yield of 4.1%; 5/122). Based on gene content and recurrence in three large cohorts [a Brazilian neurodevelopmental disorder cohort, the autism MSSNG cohort, and the Canadian-based Centre for Applied Genomics microarray database], this work strengthened the pathogenicity of 14 genes (FAT1, CAMK4, BIRC6, DPP6, CSMD1, CTNNA3, CDH8/CDH11, CDH13, OR1C1, CNTN6, CNTNAP4, FGF2 and PTPRN2) within 14 CNVs. Notably, enrichment of cell adhesion proteins to ASD etiology was identified (p < 0.05), highlighting the importance of these gene families in the etiology of ASD.

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3. DeBoth KK, Reynolds S, Lane SJ, Carretta H, Lane AE, Schaaf RC. Neurophysiological Correlates of Sensory-Based Phenotypes in ASD. Child psychiatry and human development. 2021.

Children with autism spectrum disorder frequently present with atypical behavioral responses to sensory stimuli, as well as differences in autonomic nervous system (ANS) and neuroendocrine activity. However, no one consistent pattern appears to explain these differences within this heterogeneous population. To conceptualize more homogenous ASD subgroups, sensory-based subtypes have been explored. One subtyping mechanism groups children by sensory responsivity pattern in addition to sensory domain. Differences in nervous system responsivity to sensory input within this sensory-based subtyping scheme have not yet been investigated. This exploratory study used ANS indices (respiratory sinus arrhythmia [RSA], skin conductance level) and neuroendocrine (salivary cortisol) response to examine patterns differentiating these subtypes. Significant differences in RSA were found during baseline, and during tactile, tone and movement stimuli (p < 0.05). Subtype membership was predicted by RSA changes during auditory stimulation and recovery periods (p < 0.05). Results confirm that children with an adaptive sensory responsivity subtype differ from those children with sensory processing dysfunction, however, physiological variables did not distinguish between children with different patterns of sensory processing dysfunction.

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4. Eisenberg C, Subramanian D, Afrasiabi M, Ziobro P, DeLucia J, Hirschberg PR, Shiflett MW, Santhakumar V, Tran TS. Reduced hippocampal inhibition and enhanced autism-epilepsy comorbidity in mice lacking neuropilin 2. Translational psychiatry. 2021; 11(1): 537.

The neuropilin receptors and their secreted semaphorin ligands play key roles in brain circuit development by regulating numerous crucial neuronal processes, including the maturation of synapses and migration of GABAergic interneurons. Consistent with its developmental roles, the neuropilin 2 (Nrp2) locus contains polymorphisms in patients with autism spectrum disorder (ASD). Nrp2-deficient mice show autism-like behavioral deficits and propensity to develop seizures. In order to determine the pathophysiology in Nrp2 deficiency, we examined the hippocampal numbers of interneuron subtypes and inhibitory regulation of hippocampal CA1 pyramidal neurons in mice lacking one or both copies of Nrp2. Immunostaining for interneuron subtypes revealed that Nrp2(-/-) mice have a reduced number of parvalbumin, somatostatin, and neuropeptide Y cells, mainly in CA1. Whole-cell recordings identified reduced firing and hyperpolarized shift in resting membrane potential in CA1 pyramidal neurons from Nrp2(+/-) and Nrp2(-/-) mice compared to age-matched wild-type controls indicating decrease in intrinsic excitability. Simultaneously, the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) are reduced in Nrp2-deficient mice. A convulsive dose of kainic acid evoked electrographic and behavioral seizures with significantly shorter latency, longer duration, and higher severity in Nrp2(-/-) compared to Nrp2(+/+) animals. Finally, Nrp2(+/-) and Nrp2(-/-) but not Nrp2(+/+), mice have impaired cognitive flexibility demonstrated by reward-based reversal learning, a task associated with hippocampal circuit function. Together these data demonstrate a broad reduction in interneuron subtypes and compromised inhibition in CA1 of Nrp2(-/-) mice, which could contribute to the heightened seizure susceptibility and behavioral deficits consistent with an ASD/epilepsy phenotype.

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5. Figueiredo CP, Fontes-Dantas FL, da Poian AT, Clarke JR. SARS-CoV-2-associated cytokine storm during pregnancy as a possible risk factor for neuropsychiatric disorder development in post-pandemic infants. Neuropharmacology. 2021; 201: 108841.

A strong association between perinatal viral infections and neurodevelopmental disorders has been established. Both the direct contact of the virus with the developing brain and the strong maternal immune response originated by viral infections can impair proper neurodevelopment. Coronavirus disease 2019 (COVID-19), caused by the highly-infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently responsible for a large global outbreak and is a major public health issue. While initial studies focused on the viral impact on the respiratory system, increasing evidence suggest that SARS-CoV-2 infects other organs and tissues including the mature brain. While studies continue to determine the neuropathology associated to COVID-19, the consequences of SARS-CoV-2 infection to the developing brain remain largely unexplored. The present review discusses evidence suggesting that SARS-CoV-2 infection may have persistent effects on the course of pregnancy and on brain development. Studies have shown that several proinflammatory mediators which are increased in the SARS-CoV-2-associated cytokine storm, are also modified in other viral infections known to increase the risk of neurodevelopmental disorders. In this sense, further studies should assess the genuine effects of SARS-CoV-2 infection during pregnancy and delivery along with an extended follow-up of the offspring, including neurocognitive, neuroimaging, and electrophysiological examination. It also remains to be determined whether and by which mechanisms SARS-CoV-2 intrauterine and early life infection could lead to an increased risk of developing neuropsychiatric disorders, such as autism (ASD) and schizophrenia (SZ), in the offspring.

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6. Kim MK, Park NK. Evaluating the Impact of a Multisensory Environment on Target Behaviors of Children With Autism Spectrum Disorder. Herd. 2022; 15(2): 163-79.

BACKGROUND: Worldwide, children are increasingly being diagnosed with autism spectrum disorder (ASD). The case of South Korea is not exceptional. One of the core symptoms of children with ASD is sensory reactivity issues, such as an unusual interest in the sensory aspects of the environment. One promising development in sensory enrichment for individuals with ASD is a multisensory environment (MSE). OBJECTIVES: This study investigated the influence of MSE on the target behaviors of children with ASD with different sensory characteristics in the case of South Korea. METHODS: A multiple treatment design {A-B-C-D (B + C) phases} was implemented to observe the six target behaviors of three children with ASD. The sensory environmental intervention focusing on visual and auditory stimuli was manipulated as a stimulating MSE or a relaxing MSE depending on the sensory profile of each participant. The analysis was undertaken using visual inspection with data patterns and graph slopes, which is a customary method of analyzing the single-subject design data. In addition, the means and standard deviations of the two target behaviors of each participant were analyzed together. RESULTS: The findings reveal that MSE interventions positively affected the target behaviors of children with ASD with diverse sensory characteristics. The stimulating MSE created by the integration of visual and auditory stimuli was the most effective intervention for the participants with hypo-visual and hypo-auditory sensitivities in this study. CONCLUSIONS: The MSE could be meaningful as a nonpharmaceutical therapy that could influence the daily behaviors of children with ASD.

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7. Lee J, Chang J. Oral health issues of young adults with severe intellectual and developmental disabilities and caregiver burdens: a qualitative study. BMC oral health. 2021; 21(1): 538.

BACKGROUND: Oral health maintenance is difficult to be achieved alone by patients with special needs and insufficient self-care skills. This study aims to investigate how the oral health issues of young adults with severe intellectual and developmental disabilities (IDD) affect caregiver burdens. METHODS: A qualitative research method was employed with semi-structured interviews conducted with 14 maternal caregivers of patients with severe IDD. Eleven young adults had neurofunctional disorders and three had autism spectrum disorders. All recorded data were transcribed verbatim and subjected to thematic analysis. RESULTS: Three themes emerged from the main agenda: predisposing oral dysfunction, home care challenges, and professional treatment barriers. The severity of the disabilities had an impact on oral disease risks that increased as patients aged. Participants indicated that, among the daily living activities of their patients, toothbrushing was a particular hardship due to their dysphagia and behavioral issues. Factors impacting on dental treatment indicated by caregivers included social, emotional, and financial circumstances. CONCLUSIONS: Dysphagia and behavioral issues of adult patients with severe IDD contributed to caregiver burdens in the dental care of the patients. Caregiver burdens and barriers to treatment were mutual factors hindering adequate interventions in dealing with dental problems of the patients.

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8. Martucci M, Aceti F, Giacchetti N, Sogos C. The mother-baby bond: a systematic review about perinatal depression and child developmental disorders. Rivista di psichiatria. 2021; 56(5): 223-36.

BACKGROUND: Perinatal depression is a common mental disorder, which has become a significant public health concern, especially in the western developed countries where it has a prevalence of 10-20%. As a mental illness, it does not only concern the affected mother but also the child and family. AIM: The aim of this review is to examine any developmental disorders in children of depressed mothers. METHODS: Studies were identified from the following sources: PubMed (Database 2015-2021), Psycarticles (Database 2015-2021), and Psychinfo (Database 2015-2021). Of the 388 studies considered, 32 full-text articles have been analysed, and 22 have been included in the review. RESULTS: Results suggest an increased risk of child emotional dysregulation and socio-emotional problems. Several studies reported an increased risk of cognitive, motor and language delay. Moreover, some studies suggest behaviour problems in preschool-age for the children of depressed mothers. CONCLUSIONS: These evidences lead to the importance of including maternal mental health into primary health care and adequately addressing the dyad to treat depressed mothers and prevent consequences for child development.

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9. Reidenberg BE, Hirsch K, Costello CM, Russo M, Reilly M, Murphy P. Drive through COVID19 vaccination for developmentally disabled persons. Vaccine. 2022; 40(16): 2365-6.

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10. Schendel D, Munk Laursen T, Albiñana C, Vilhjalmsson B, Ladd-Acosta C, Fallin MD, Benke K, Lee B, Grove J, Kalkbrenner A, Ejlskov L, Hougaard D, Bybjerg-Grauholm J, Baekvad-Hansen M, Børglum AD, Werge T, Nordentoft M, Mortensen PB, Agerbo E. Evaluating the interrelations between the autism polygenic score and psychiatric family history in risk for autism. Autism research : official journal of the International Society for Autism Research. 2022; 15(1): 171-82.

Psychiatric family history or a high autism polygenic risk score (PRS) have been separately linked to autism spectrum disorder (ASD) risk. The study aimed to simultaneously consider psychiatric family history and individual autism genetic liability (PRS) in autism risk. We performed a case-control study of all Denmark singleton births, May 1981-December 2005, in Denmark at their first birthday and a known mother. Cases were diagnosed with ASD before 2013 and controls comprised a random sample of 30,000 births without ASD, excluding persons with non-Denmark-born parents, missing ASD PRS, non-European ancestry. Adjusted odds ratios (aOR) were estimated for ASD by PRS decile and by psychiatric history in parents or full siblings (8 mutually-exclusive categories) using logistic regression. Adjusted ASD PRS z-score least-squares means were estimated by psychiatric family history category. ASD risk (11,339 ASD cases; 20,175 controls) from ASD PRS was not substantially altered after accounting for psychiatric family history (e.g., ASD PRS 10th decile aOR: 2.35 (95% CI 2.11-2.63) before vs 2.11 (95% CI 1.91-2.40) after adjustment) nor from psychiatric family history after accounting for ASD PRS (e.g., ASD family history aOR: 6.73 (95% CI 5.89-7.68) before vs 6.32 (95% CI 5.53-7.22) after adjustment). ASD risk from ASD PRS varied slightly by psychiatric family history. While ASD risk from psychiatric family history was not accounted for by ASD PRS and vice versa, risk overlap between the two factors will likely increase as measures of genetic risk improve. The two factors are best viewed as complementary measures of family-based autism risk. LAY SUMMARY: Autism risk from a history of mental disorders in the immediate family was not explained by a measure of individual genetic risk (autism polygenic risk score) and vice versa. That is, genetic risk did not appear to overlap family history risk. As genetic measures for autism improve then the overlap in autism risk from family history versus genetic factors will likely increase, but further study may be needed to fully determine the components of risk and how they are inter-related between these key family factors. Meanwhile, the two factors may be best viewed as complementary measures of autism family-based risk.

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11. Schmidt S. Autism in Three Dimensions: Using Brain Organoids to Study Potential Gene-Environment Interactions. Environmental health perspectives. 2021; 129(10): 104003.

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12. Yang H, Yang S, Kang Q, Yang L, Liao H, Wu L. MORC2 gene de novo mutation leads to Charcot-Marie-Tooth disease type 2Z: A pediatric case report and literature review. Medicine. 2021; 100(37): e27208.

RATIONALE: Mutations of the MORC2 gene have most commonly been associated with autosomal-dominant Charcot-Marie-Tooth disease type 2Z (CMT 2Z), while the impact of MORC2 mutations in CMT 2Z on neuronal biology and their phenotypic consequences in patients remain to be clarified. PATIENT CONCERNS: We reported a 27-month-old child with a developmental lag of more than 1 year. He had progressive fatigue for 4 months, accompanied by dysphagia, choking while eating, and progressive aggravation. A genetic study revealed a de novo variant of MORC2, which has not yet been reported. DIAGNOSIS: According to the child’s clinical manifestations, genetic pattern, and American College of Medical Genetics and Genomics pathogenicity analysis, the patient was diagnosed with CMT 2Z caused by MORC2 gene mutation. INTERVENTIONS: Mitochondrial cocktail therapy (arginine, vitamin B1 tablets, vitamin B2 tablets, coenzyme Q10 capsules, L-carnitine oral liquid, idebenone tablets, etc) was given. OUTCOMES: Mitochondrial cocktail therapy did not significantly improve the child’s condition, head magnetic resonance imaging lesions were not significantly improved at outpatient follow-up more than 1 month later, and the lesions were basically unchanged. LESSONS: The clinical manifestations of the disease were similar to those of Leigh syndrome, and they were not significantly improved by cocktail therapy. This site has not been reported in the literature domestically or abroad, and the pathogenesis of CMT 2Z caused by this site mutation is indeed not related to mitochondrial dysfunction. Our study is helpful for clinicians with regard to the differential diagnosis of Leigh syndrome and CMT 2Z and improvement of clinicians’ understanding of CMT 2Z disease.

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13. Zandam H, Mitra M, Akobirshoev I, Li FS, Ne’eman A. Infectious Diseases-Related Emergency Department Visits Among Non-Elderly Adults with Intellectual and Developmental Disabilities in the United States: Results from the National Emergency Department Sample, 2016. Population health management. 2021.

Emerging evidence on the disproportionate impact of COVID-19 on people with intellectual and developmental disabilities (IDD) points to the underlying risk and burden of infectious diseases (IDs) in this population. The objective of this study was to examine the risk of ID-related emergency department (ED) visits, subsequent hospitalizations, and hospital-based mortality during ID-related visits among adults with IDD compared to those without IDD. The authors conducted a retrospective study using data from the 2016 Nationwide Emergency Department Sample. The sample included 94,928 adults with IDD identified using ICD-10-CM codes, and age- and sex-matched 284,763 non-IDD adults in a 1:3 case-control ratio. A Poisson regression model was used to compare the risk of ID-related ED visits, subsequent hospitalizations, and hospital-based mortality during ID-related visits between adults with and without IDD. Covariates included sociodemographic and hospital characteristics. Results showed that adults with IDD are at a higher risk for ID-related ED visits, subsequent hospitalization, and mortality during ID-related ED visits compared to non-IDD adults. Adults with IDD continued to experience higher risks even after accounting for sociodemographic, hospital, and clinical characteristics. Septicemia and respiratory tract infections are the leading causes of ED visits, hospitalization, and mortality. This study found substantial disparities in ID-related ED visits, subsequent hospitalization, and mortality among the burdens for adults with IDD. These observations underscore the importance of integrated strategies to reduce ID-related morbidity among adults with IDD.

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