1. Socioeconomic Factors Account for Variability in Language Skills in Preschoolers with Autism Spectrum Disorders: Erratum. Journal of developmental and behavioral pediatrics : JDBP. 2021; 42(5): 427-8.

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2. Anugu V, Ringhisen J, Johnson B. Autism Case Report: Cause and Treatment of « High Opioid Tone » Autism. Frontiers in psychology. 2021; 12: 657952.

Introduction: Neurobiological systems engineering models are useful for treating patients. We show a model of « high opioid tone » autism and present a hypothesis about how autism is caused by administration of opioids during childbirth. Main Symptoms: Clinical diagnosis of autism in a 25 year old man was confirmed by a Social Responsiveness Scale (SRS) self-rating of 79, severe, and a Social Communications Questionnaire (SCQ-2) by the patient’s father scoring 27. Cold pressor time (CPT) was 190 seconds-unusually long, consonant with the high pain tolerance of autism. Therapeutic Intervention and Outcomes: At naltrexone 50 mg/day SRS fell to 54 and SCQ–2-9; both non-significant. CPT fell to 28, repeat 39 s. Improved relatedness was experienced ambivalently, understood as feelings never before experienced-causing pain. Non-compliance with naltrexone was followed by cutting open his palm and drinking alcoholically. Transference focused psychotherapy has helped him remain naltrexone-compliant while he works on issues of identity and relatedness. Conclusion: The model suggests studies that could be conducted to both prevent and treat this form of autism.

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3. Ashraf A, Iftikhar R. Emotional response bias, autistic traits and paranormal beliefs in patients with Obsessive Compulsive Disorder. JPMA The Journal of the Pakistan Medical Association. 2021; 71(6): 1596-600.

OBJECTIVE: To find the relationship involving autistic traits, paranormal beliefs and emotional response bias in obsessive compulsive disorder patients. METHOD: The cross-sectional quasi-experimental study was conducted from November 2017 to November 2018 at the Government College University, Lahore, Pakistan, and comprised patients with obsessive compulsive disorder and healthy controls from the general population aged 20-40 years. Data was collected using the self-reporting Autism Spectrum Quotient, the Revised Paranormal Belief Scale, the Emotional Recognition Task and the Obsessive Compulsive Disorder symptom checklist. Data was analysed using SPSS 20. RESULTS: Of the 140 participants, there were 70(50%) patients and as many controls. Overall, there were 72(52%) males and 68(48%) females. High level of autistic traits (p<0.001) and paranormal beliefs (p<0.001) had a significant impact on obsessive compulsive disorder. Impairments in recognition of emotions were related to the presence of high autistic traits and obsessive compulsive symptoms in the patients group (p<0.05). Emotion of disgust (p<0.001) was significantly impaired in the patients, while the differences were not significant in terms of emotions of happiness and surprise (p>0.05). CONCLUSIONS: Autistic traits, paranormal beliefs and emotional response bias were found to have a significant relationship in obsessive compulsive disorder patients.

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4. Bejarano-Martín Á, Canal-Bedia R, Magán-Maganto M, Hernández Fabián A, Calvarro Castañeda AL, Manso de Dios S, Malmierca García P, Díez Villoria E, Jenaro Río C, Posada de la Paz M. Correction to: Effect of a Focused Social and Communication Intervention on Preterm Children with ASD: A Pilot Study. Journal of autism and developmental disorders. 2022; 52(4): 1741.

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5. Brieger KK, Bakulski KM, Pearce CL, Baylin A, Dou JF, Feinberg JI, Croen LA, Hertz-Picciotto I, Newschaffer CJ, Fallin MD, Schmidt RJ. The Association of Prenatal Vitamins and Folic Acid Supplement Intake with Odds of Autism Spectrum Disorder in a High-Risk Sibling Cohort, the Early Autism Risk Longitudinal Investigation (EARLI). Journal of autism and developmental disorders. 2021.

We examined maternal prenatal vitamin use or supplemental folic acid intake during month one of pregnancy for association with autism spectrum disorder (ASD) in the Early Autism Risk Longitudinal Investigation, an enriched-risk pregnancy cohort. Total folic acid intake was calculated from monthly prenatal vitamins, multivitamins, and other supplement reports. Clinical assessments through age 3 years classified children as ASD (n = 38) or non-ASD (n = 153). In pregnancy month one, prenatal vitamin use (59.7%) was not significantly associated with odds of ASD (OR = 0.70, 95%CI 0.32, 1.53). Sample size was limited and residual confounding was possible. Given the estimated effect sizes in this and previous work, prenatal vitamin intake during early pregnancy could be a clinically useful preventative measure for ASD.

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6. Chen F, Cheung CC, Peng G. Linguistic Tone and Non-Linguistic Pitch Imitation in Children with Autism Spectrum Disorders: A Cross-Linguistic Investigation. Journal of autism and developmental disorders. 2022; 52(5): 2325-43.

The conclusions on prosodic pitch features in autism spectrum disorders (ASD) have primarily been derived from studies in non-tonal language speakers. This cross-linguistic study evaluated the performance of imitating Cantonese lexical tones and their non-linguistic (nonspeech) counterparts by Cantonese- and Mandarin-speaking children with and without ASD. Acoustic analyses showed that, compared with typically developing peers, children with ASD exhibited increased pitch variations when imitating lexical tones, while performed similarly when imitating the nonspeech counterparts. Furthermore, Mandarin-speaking children with ASD failed to exploit the phonological knowledge of segments to improve the imitation accuracy of non-native lexical tones. These findings help clarify the speech-specific pitch processing atypicality and phonological processing deficit in tone-language-speaking children with ASD.

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7. De Risi M, Tufano M, Alvino FG, Ferraro MG, Torromino G, Gigante Y, Monfregola J, Marrocco E, Pulcrano S, Tunisi L, Lubrano C, Papy-Garcia D, Tuchman Y, Salleo A, Santoro F, Bellenchi GC, Cristino L, Ballabio A, Fraldi A, De Leonibus E. Altered heparan sulfate metabolism during development triggers dopamine-dependent autistic-behaviours in models of lysosomal storage disorders. Nature communications. 2021; 12(1): 3495.

Lysosomal storage disorders characterized by altered metabolism of heparan sulfate, including Mucopolysaccharidosis (MPS) III and MPS-II, exhibit lysosomal dysfunctions leading to neurodegeneration and dementia in children. In lysosomal storage disorders, dementia is preceded by severe and therapy-resistant autistic-like symptoms of unknown cause. Using mouse and cellular models of MPS-IIIA, we discovered that autistic-like behaviours are due to increased proliferation of mesencephalic dopamine neurons originating during embryogenesis, which is not due to lysosomal dysfunction, but to altered HS function. Hyperdopaminergia and autistic-like behaviours are corrected by the dopamine D1-like receptor antagonist SCH-23390, providing a potential alternative strategy to the D2-like antagonist haloperidol that has only minimal therapeutic effects in MPS-IIIA. These findings identify embryonic dopaminergic neurodevelopmental defects due to altered function of HS leading to autistic-like behaviours in MPS-II and MPS-IIIA and support evidence showing that altered HS-related gene function is causative of autism.

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8. Dempsey J, Ahmed K, Simon AR, Hayutin LG, Monteiro S, Dempsey AG. Adaptive Behavior Profiles of Intellectually Gifted Children with Autism Spectrum Disorder. Journal of developmental and behavioral pediatrics : JDBP. 2021; 42(5): 374-9.

OBJECTIVE: The purpose of this study is to identify whether the well-described pattern of declining adaptive functioning across age among children with autism spectrum disorder (ASD) also exists among intellectually gifted children with ASD because their cognitive abilities might serve as a protective factor. METHODS: Data from the Simons Simplex Collection were used to identify 51 participants with full-scale intelligence (IQ) scores of 130 or above with this group labeled as the intellectually gifted range (IGR). Two comparison samples of children with IQs in the intellectual disability range (IDR; < 70 Standard Score [SS]) and average range (AR; 85-115 SS) were created based on matching of age (±2 years), maternal education level, and sex. RESULTS: Multivariate analysis of variance indicated a main overall effect for the IQ group on a measure of adaptive skills (Λ = 0.61, F(6, 296), p < 0.001). Post hoc comparisons revealed that the IDR group scored lower on all subscales than the AR and IGR groups, but the scores between the latter groups did not differ from one another in socialization and daily living skills (DLS) domains. Age was negatively correlated with adaptive communication scores in all groups but only associated with socialization and DLS domain scores in the IGR group (r = -0.51 and -0.48, respectively). CONCLUSION: The findings suggest that intellectual giftedness does not serve as a protective factor against age-related declines in adaptive functioning among individuals with ASD.

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9. Falcone C, Mevises NY, Hong T, Dufour B, Chen X, Noctor SC, Martínez Cerdeño V. Neuronal and glial cell number is altered in a cortical layer-specific manner in autism. Autism : the international journal of research and practice. 2021; 25(8): 2238-53.

The cerebral cortex affected with autism spectrum disorder presents changes in the number of neurons and glia cells, possibly leading to a dysregulation of brain circuits and affecting behavior. However, little is known about cell number alteration in specific layers of the cortex in autism spectrum disorder. We found an increase in the number of neurons and a decrease in the number of astrocytes in specific layers of the prefrontal cortex in postmortem human brains from autism spectrum disorder cases. We hypothesize that this may be due to a failure in neural stem cells to shift differentiation from neurons to glial cells during prenatal brain development. These data provide key anatomical findings that contribute to the bases of autism spectrum disorder pathogenesis.

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10. Hui T, Goh TJ, Sung M. Clinical presentations of social communication disorder: A case series. Asian journal of psychiatry. 2021; 62: 102718.

Social Communication Disorder (SCD) is a new DSM-5 diagnostic category poorly understood by clinicians. We describe a case series of four individuals diagnosed with SCD to identify common characteristics and differences in presentations of the disorder. All cases had deficits in the area of social communication, and sub-threshold level of restricted and repetitive behaviours, not sufficient to meet criteria for Autism Spectrum Disorder (ASD). All cases presented with at least one mental health co-morbid condition. There are significant overlaps in clinical presentation between SCD and ASD. It is imperative that accurate diagnostic tools and effective intervention approaches of SCD be developed.

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11. Liu T, Wang FS, Cheah FSH, Gu Y, Shaw M, Law HY, Tay SKH, Lee CG, Nelson DL, Gecz J, Chong SS. Simultaneous Screening of the FRAXA and FRAXE Loci for Rapid Detection of FMR1 CGG and/or AFF2 CCG Repeat Expansions by Triplet-Primed PCR. The Journal of molecular diagnostics : JMD. 2021; 23(8): 941-51.

Moderate to hyper-expansion of trinucleotide repeats at the FRAXA and FRAXE fragile sites, with or without concurrent hypermethylation, has been associated with intellectual disability and other conditions. Unlike molecular diagnosis of FMR1 CGG repeat expansions in FRAXA, current detection of AFF2 CCG repeat expansions in FRAXE relies on low-throughput and otherwise inefficient techniques combining Southern blot analysis and PCR. A novel triplet-primed PCR assay was developed for simultaneous screening for trinucleotide repeat expansions at the FRAXA and FRAXE fragile sites, and was validated using archived clinical samples of known FMR1 and AFF2 genotypes. Population samples and FRAXE-affected samples were sequenced for the evaluation of variations in the AFF2 CCG repeat structure. The duplex assay accurately identified expansions at the FMR1 and AFF2 trinucleotide repeat loci. On Sanger sequencing of the AFF2 CCG repeat, the single-nucleotide polymorphism variant rs868914124(C) that effectively adds two CCG repeats at the 5′-end, was enriched in the Malay population and with short repeats (<11 CCGs), and was present in all six expanded AFF2 alleles of this study. All expanded AFF2 alleles contained multiple non-CCG interruptions toward the 5'-end of the repeat. A sensitive, robust, and rapid assay has been developed for the simultaneous detection of expansion mutations at the FMR1 and AFF2 trinucleotide repeat loci, simplifying screening for FRAXA- and FRAXE-associated disorders.

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12. McCutcheon RA, Brown K, Nour MM, Smith SM, Veronese M, Zelaya F, Osugo M, Jauhar S, Hallett W, Mehta MM, Howes OD. Dopaminergic organization of striatum is linked to cortical activity and brain expression of genes associated with psychiatric illness. Science advances. 2021; 7(24).

Dopamine signaling is constrained to discrete tracts yet has brain-wide effects on neural activity. The nature of this relationship between local dopamine signaling and brain-wide neuronal activity is not clearly defined and has relevance for neuropsychiatric illnesses where abnormalities of cortical activity and dopamine signaling coexist. Using simultaneous PET-MRI in healthy volunteers, we find strong evidence that patterns of striatal dopamine signaling and cortical blood flow (an index of local neural activity) contain shared information. This shared information links amphetamine-induced changes in gradients of striatal dopamine receptor availability to changes in brain-wide blood flow and is informed by spatial patterns of gene expression enriched for genes implicated in schizophrenia, bipolar disorder, and autism spectrum disorder. These results advance our knowledge of the relationship between cortical function and striatal dopamine, with relevance for understanding pathophysiology and treatment of diseases in which simultaneous aberrations of these systems exist.

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13. McKenna BG, Huang Y, Vervier K, Hofammann D, Cafferata M, Al-Momani S, Lowenthal F, Zhang A, Koh JY, Thenuwara S, Brueggeman L, Bahl E, Koomar T, Pottschmidt N, Kalmus T, Casten L, Thomas TR, Michaelson JJ. Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts. Molecular autism. 2021; 12(1): 43.

BACKGROUND: Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) display a strong male bias. Androgen exposure is profoundly increased in typical male development, but it also varies within the sexes, and previous work has sought to connect morphological proxies of androgen exposure, including digit ratio and facial morphology, to neurodevelopmental outcomes. The results of these studies have been mixed, and the relationships between androgen exposure and behavior remain unclear. METHODS: Here, we measured both digit ratio masculinity (DRM) and facial landmark masculinity (FLM) in the same neurodevelopmental cohort (N = 763) and compared these proxies of androgen exposure to clinical and parent-reported features as well as polygenic risk scores. RESULTS: We found that FLM was significantly associated with NDD diagnosis (ASD, ADHD, ID; all [Formula: see text]), while DRM was not. When testing for association with parent-reported problems, we found that both FLM and DRM were positively associated with concerns about social behavior ([Formula: see text], [Formula: see text]; [Formula: see text], [Formula: see text], respectively). Furthermore, we found evidence via polygenic risk scores (PRS) that DRM indexes masculinity via testosterone levels ([Formula: see text], [Formula: see text]), while FLM indexes masculinity through a negative relationship with sex hormone binding globulin (SHBG) levels ([Formula: see text], [Formula: see text]). Finally, using the SPARK cohort (N = 9419) we replicated the observed relationship between polygenic estimates of testosterone, SHBG, and social functioning ([Formula: see text], [Formula: see text], and [Formula: see text], [Formula: see text] for testosterone and SHBG, respectively). Remarkably, when considered over the extremes of each variable, these quantitative sex effects on social functioning were comparable to the effect of binary sex itself (binary male: [Formula: see text]; testosterone: [Formula: see text] from 0.1%-ile to 99.9%-ile; SHBG: [Formula: see text] from 0.1%-ile to 99.9%-ile). LIMITATIONS: In the devGenes and SPARK cohorts, our analyses rely on indirect, rather than direct measurement of androgens and related molecules. CONCLUSIONS: These findings and their replication in the large SPARK cohort lend support to the hypothesis that increasing net androgen exposure diminishes capacity for social functioning in both males and females.

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14. McLay LL, France KG, Blampied NM, Hunter JE, van Deurs JR, Woodford EC, Gibbs R, Lang R. Collateral Child and Parent Effects of Function‑Based Behavioral Interventions for Sleep Problems in Children and Adolescents with Autism. Journal of autism and developmental disorders. 2022; 52(5): 2258-73.

This study follows McLay et al., Journal of Autism and Developmental Disorders, (2020) to investigate whether the function-based behavioral sleep interventions received by 41 children and adolescents with autism spectrum disorder (ASD) produced collateral improvements in ASD severity, internalizing and externalizing symptoms and parent relationship quality, ratings of depression, anxiety and stress, and personal sleep quality. Concomitant with reduced sleep problem severity, improvements were found in children’s internalizing and externalizing behavior and ASD symptom severity. Small improvements were also found in maternal sleep quality and parental stress. There was little change in parental relationship quality post-treatment, possibly reflecting high baseline scores. Overall, collateral benefits were generally small but positive, consistent with the limited extant research, and underscore the importance of investigating collateral effects across a range of variables.

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15. Saul J, Norbury C. A Randomized Case Series Approach to Testing Efficacy of Interventions for Minimally Verbal Autistic Children. Frontiers in psychology. 2021; 12: 621920.

BACKGROUND: Randomized Controlled Trials (RCTs) are the gold standard for assessing whether an intervention is effective; however, they require large sample sizes in order to detect small effects. For rare or complex populations, we advocate a case series approach as a more realistic and useful first step for intervention evaluation. We consider the importance of randomization to such designs, and advocate for the use of Randomization Tests and Between Case Effect Sizes to provide a robust and statistically powerful evaluation of outcomes. In this tutorial, we describe the method, procedures, and analysis code necessary to conduct robust single case series, using an empirical example with minimally verbal autistic children. METHOD: We applied a pre-registered (https://osf.io/9gvbs) randomized baseline design with between-case effect size to a case series (n = 19), to test the efficacy of a novel, parent-mediated, app-based speech production intervention (BabbleBooster) for minimally verbal autistic children. Parent-rated probe scores were used to densely sample performance accuracy over time. RESULTS: Parents were able to reliably code their children’s speech productions using BabbleBooster. A non-significant Randomization Test and small Between-Case Effect Size (d = 0.267), suggested there was no evidence that BabbleBooster improved speech production in minimally verbal autistic children, relative to baseline scores, during this brief period of intervention. CONCLUSION: The current analyses exemplify a more robust approach to examining treatment effects in rare or complex populations, where RCT may be difficult or premature to implement. To facilitate adoption of this method by researchers and practitioners, we provide analysis code that can be adapted using open source R packages. Future studies could use this case series design to evaluate interventions aiming to improve speech and language outcomes for minimally verbal autistic children, and other heterogeneous and hard to reach populations.

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16. Shannon CA, Olsen LL, Hole R, Rush KL. « There’s nothing here »: Perspectives from rural parents promoting safe active recreation for children living with autism spectrum disorders. Research in developmental disabilities. 2021; 115: 103998.

BACKGROUND: Children with autism spectrum disorder (ASD) and their families experience challenges and barriers at multiple levels that influence their activity participation. The purpose of this study was to develop understanding about factors influencing how families can promote safe, active recreation for their children 3-12 years living with ASD across rural settings and how supports for these families can be enhanced. METHODS: This qualitative study used an interpretive descriptive approach. Twelve in-depth, semi-structured interviews with parents of children with ASD were conducted. Data was analyzed thematically. RESULTS: Four main themes emerged: 1) ASD specific child vulnerabilities impeding safe recreation. 2) Importance of safe outdoor spaces in rural settings for children with ASD. 3) Diverse parent strategies to address risks and needs. 4) Perceived needs for training of recreation providers. CONCLUSION: Findings highlight family-centred priority issues including parental safety concerns related to elopement and risk of injury linked to environmental and outdoor hazards prominent in rural settings. Autism awareness and recreational training is needed and could incorporate collaborative development of child specific safety plans to foster inclusive opportunities. Program planners can use this information to encourage policy making to aid families’ safe activity participation.

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17. Shu L, Xu Y, Tian Q, Chen Y, Wang Y, Xi H, Wang H, Xiao N, Mao X. A Frameshift Variant in the SEMA6B Gene Causes Global Developmental Delay and Febrile Seizures. Neuroscience bulletin. 2021; 37(9): 1357-60.

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18. South M, Hanley M, Normansell-Mossa K, Russell NCC, Cawthorne T, Riby DM. « Intolerance of uncertainty » mediates the relationship between social profile and anxiety in both Williams syndrome and autism. Autism research : official journal of the International Society for Autism Research. 2021; 14(9): 1986-95.

Anxiety is the most significant mental health concern for both Williams syndrome (WS) and autism. Whilst WS and autism are characterized by some syndrome-specific social differences, less is known about cross-syndrome profiles of anxiety symptoms. Previous research has shown that Intolerance of Uncertainty (IU) is a core mechanism of anxiety maintenance for clinically anxious populations and for autistic children, adolescents, and adults. The only published study in this area for WS has shown some similar patterns-with an added emphasis on the role of sensory sensitivities-in a sample of older teens and adults (mean age = 24), with the authors highlighting the need for younger samples to consider developmental influences. Here we report a cross-syndrome, cross-sectional mediation analyses of children diagnosed with WS or autism, including data from parent surveys of 90 children with WS (n = 48) or autism (n = 42). Group differences showed higher trait levels on all measures for the autism group. Importantly, the relationship between social profile and anxiety was fully mediated by IU level for both groups. This suggests possible similar core mechanisms underlying anxiety in these conditions, and the possibility of generalized intervention approaches especially related to managing distress related to uncertainty in multiple contexts. LAY SUMMARY: Autism and Williams Syndrome share some similarities in social profile and also in anxiety traits, but there are also some key differences as well. Comparing them side-by-side at the same time improved identification of ways to reduce feelings of anxiety. We found that the intolerance of uncertainty affected the relationship between social profile and anxiety in the same way for young children diagnosed with autism or Williams syndrome, meaning that intervention approaches could be similar for both.

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19. Spina Nagy G, Kawamoto EM, Bridi JC. The role of PTEN signaling in synaptic function: Implications in autism spectrum disorder. Neuroscience letters. 2021; 759: 136015.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) regulates several cellular processes including survival, proliferation, and metabolism. In the brain, PTEN is a key modulator of synaptic function, and is involved in regulating synaptogenesis, connectivity, and synaptic plasticity. Herein we discuss how alterations in PTEN can disturb these mechanisms, thus compromising normal synaptic function and consequently contributing to behavioral and cognitive phenotypes observed in autism spectrum disorder (ASD). As the role of PTEN in synaptic function is linked to ASD, a deeper understanding of this interaction will shed light on the pathological mechanisms involved in ASD, contributing to the development of new therapies.

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20. Tran AT, Del Rosario M, Nosco E, Li Y, Senturk D, McDonald NM, Wilson RB, Dapretto M, Jeste SS. Early concerns in parents of infants at risk for autism. Developmental medicine and child neurology. 2021; 63(12): 1410-6.

AIM: To examine parental concerns about children at increased familial risk (i.e. high risk) of developing autism spectrum disorder (ASD) in early infancy. METHOD: ASD-related and general parental concerns were prospectively collected for 76 infants at ages 1.5, 3, 6, 9, 12, and 18 months. Outcome classification was determined at 36 months. Analyses included generalized linear mixed models and qualitative evaluation of parental concerns in relation to risk status (high vs low risk) and outcome classification within the high-risk group (atypically developing vs typically developing) over time. RESULTS: Most parents had no concerns at 1.5 (high risk 71%, low risk 87%) and 3 months (high risk 77%, low risk 86%). Beginning at 6 months, parents of high-risk infants reported more ASD-related (p<0.001) and general concerns (p=0.003) than parents of low-risk infants. Beginning at 12 months, parents of high-risk atypically developing infants reported more ASD-related concerns than parents of high-risk typically developing infants (p=0.013). INTERPRETATION: Clinicians should elicit parental concerns and provide support, as parents are worried about their high-risk infants by age 6 months. Additionally, parents' abilities to identify concerns that are suggestive of ASD by age 12 months may aid in earlier screening and intervention. What this paper adds Most parents did not report concerns during early infancy. By 6 months, parents of high-risk infants reported autism spectrum disorder (ASD)-related and general concerns. By 12 months, parents of high-risk atypically developing infants identified ASD-related concerns.

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21. Vik T. [Persons with intellectual disabilities and use of coercion with COVID-19 vaccination]. Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke. 2021; 141(9).

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