1. Andrade C. Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, and Other Neurodevelopmental Outcomes Associated With Antipsychotic Drug Exposure During Pregnancy. The Journal of clinical psychiatry. 2022; 83(3).

Between 0.3%-4.6% of women use antipsychotic (AP) drugs during pregnancy. Two large, retrospective, population-based cohort studies, conducted in Nordic countries and in the US, examined the risk of neurodevelopmental disorders (NDDs) following gestational exposure to APs. The Nordic study found that, in unadjusted analyses, exposure to APs during pregnancy was associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in offspring; that the risk all but disappeared after adjusting for covariates; and that the risk appeared to be related to maternal major mental illness rather than to gestational exposure to APs. The US study also found that, in unadjusted analyses, gestational exposure to APs was associated with an increased risk of almost all of the study-specified NDDs in offspring; however, after adjusting for covariates, the risks were no longer meaningfully increased and, importantly, were no longer statistically significant for ADHD and ASD. Thus, these 2 studies suggest that gestational exposure to APs is a marker of NDD risk in offspring rather than a potential cause. Whereas a small but significantly increased risk was identified for aripiprazole in the US study, the signal was inconsistent across analyses, and confounding due to maternal mental illness was not ruled out. Previous studies have suggested that the use of APs during pregnancy is not associated with an increased risk of major congenital malformations and other adverse gestational outcomes. Considering the potential harm and suffering associated with major mental illness and the very low risks associated with AP use during pregnancy, initiation or continuation of APs appears to carry a favorable risk-benefit ratio in pregnant women who need these drugs; however, decision-making should be shared between patients, their caregivers, and the treating team.

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2. Berecki G, Howell KB, Heighway J, Olivier N, Rodda J, Overmars I, Vlaskamp DRM, Ware TL, Ardern-Holmes S, Lesca G, Alber M, Veggiotti P, Scheffer IE, Berkovic SF, Wolff M, Petrou S. Functional correlates of clinical phenotype and severity in recurrent SCN2A variants. Communications biology. 2022; 5(1): 515.

In SCN2A-related disorders, there is an urgent demand to establish efficient methods for determining the gain- (GoF) or loss-of-function (LoF) character of variants, to identify suitable candidates for precision therapies. Here we classify clinical phenotypes of 179 individuals with 38 recurrent SCN2A variants as early-infantile or later-onset epilepsy, or intellectual disability/autism spectrum disorder (ID/ASD) and assess the functional impact of 13 variants using dynamic action potential clamp (DAPC) and voltage clamp. Results show that 36/38 variants are associated with only one phenotypic group (30 early-infantile, 5 later-onset, 1 ID/ASD). Unexpectedly, we revealed major differences in outcome severity between individuals with the same variant for 40% of early-infantile variants studied. DAPC was superior to voltage clamp in predicting the impact of mutations on neuronal excitability and confirmed GoF produces early-infantile phenotypes and LoF later-onset phenotypes. For one early-infantile variant, the co-expression of the α(1) and β(2) subunits of the Na(v)1.2 channel was needed to unveil functional impact, confirming the prediction of 3D molecular modeling. Neither DAPC nor voltage clamp reliably predicted phenotypic severity of early-infantile variants. Genotype, phenotypic group and DAPC are accurate predictors of the biophysical impact of SCN2A variants, but other approaches are needed to predict severity.

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3. Bourson L, Prevost C. Characteristics of restricted interests in girls with ASD compared to boys: a systematic review of the literature. European child & adolescent psychiatry. 2022.

The existence of a female phenotype profile in autistic spectrum disorder is one of the current hypotheses to explain the diagnostic discrepancy between men and women. In this context, an international literature review was carried out to evidence and describe the characteristics of restricted interests found in girls with autistic spectrum disorder. A documentary search was conducted on PubMed and a systematic literature review was carried out based on the PRISMA methodology. We selected studies with a population of boys and girls diagnosed as autistic according to the DSM-IV or the DSM-5, in which quantitative and descriptive comparisons of restricted interests, according to gender were carried out. Nineteen studies were found to be relevant. Fifteen enabled a refining of the characteristics of restricted interests among females: fewer restricted interests were identified in comparison with boys, and the autistic girls’ interests seem to be closer to those of neurotypical girls than to those of autistic boys, which thus led to more complex screening. Age and Intelligence quotient seem to be two factors that trigger variations in restricted interests differently according to gender. Representations among professionals also have an impact on diagnoses among girls. For future research, one of the perspectives could be a comparison between girls with autism and neurotypical girls to limit gender bias. The present results contribute to potentially extending knowledge of a female phenotypical profile in autism and show the need to improve the general population’s awareness, to improve health professionals’ training and possibly to revise the diagnostic tools.

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4. Carpita B, Nardi B, Palego L, Cremone IM, Massimetti G, Carmassi C, Betti L, Giannaccini G, Dell’Osso L. Kynurenine pathway and autism spectrum phenotypes: an investigation among adults with Autism spectrum disorder and their first-degree relatives. CNS spectrums. 2022: 1-40.

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5. Collins J, Horton K, Gale-St Ives E, Murphy G, Barnoux M. A Systematic Review of Autistic People and the Criminal Justice System: An Update of King and Murphy (2014). Journal of autism and developmental disorders. 2022.

The purpose of this paper was to determine whether recommendations made by King & Murphy (Journal of Autism and Developmental Disorders 44:2717-2733, 2014) in their review of the evidence on autistic people in contact with the criminal justice system (CJS) have been addressed. Research published since 2013 was systematically examined and synthesised. The quality of 47 papers was assessed using the Mixed Methods Appraisal Tool. Findings suggest a limited amount of good quality research has been conducted that has focused on improving our understanding of autistic people in contact with the CJS since 2013. Methodological limitations make direct comparisons between autistic and non-autistic offenders difficult. Autistic people commit a range of crimes and appear to have unique characteristics that warrant further exploration (i.e., vulnerabilities, motivations for offending).

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6. Del Bianco T, Mason L, Lai MC, Loth E, Tillmann J, Charman T, Hayward H, Gleissl T, Buitelaar JK, Murphy DGM, Baron-Cohen S, Bölte S, Johnson MH, Jones EJH. Unique dynamic profiles of social attention in autistic females. Journal of child psychology and psychiatry, and allied disciplines. 2022.

BACKGROUND: Social attention affords learning opportunities across development and may contribute to individual differences in developmental trajectories, such as between male and female individuals, and in neurodevelopmental conditions, such as autism. METHODS: Using eye-tracking, we measured social attention in a large cohort of autistic (n = 123) and nonautistic females (n = 107), and autistic (n = 330) and nonautistic males (n = 204), aged 6-30 years. Using mixed Growth Curve Analysis, we modelled sex and diagnostic effects on the temporal dynamics of proportional looking time to three types of social stimuli (lean-static, naturalistic-static, and naturalistic-dynamic) and examined the link between individual differences and dimensional social and nonsocial autistic traits in autistic females and males. RESULTS: In the lean-static stimulus, average face-looking was higher in females than in males of both autistic and nonautistic groups. Differences in the dynamic pattern of face-looking were seen in autistic vs. nonautistic females, but not males, with face-looking peaking later in the trial in autistic females. In the naturalistic-dynamic stimulus, average face-looking was higher in females than in males of both groups; changes in the dynamic pattern of face looking were seen in autistic vs. nonautistic males, but not in females, with a steeper peak in nonautistic males. Lower average face-looking was associated with higher observer-measured autistic characteristics in autistic females, but not in males. CONCLUSIONS: Overall, we found stronger social attention in females to a similar degree in both autistic and nonautistic groups. Nonetheless, the dynamic profiles of social attention differed in different ways in autistic females and males compared to their nonautistic peers, and autistic traits predicted trends of average face-looking in autistic females. These findings support the role of social attention in the emergence of sex-related differences in autistic characteristics, suggesting an avenue to phenotypic stratification.

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7. Dufour A, Dumon C, Gouty-Colomer LA, Eftekhari S, Ferrari DC, Ben-Ari Y. Prenatal reduction of E14.5 embryonically fate-mapped pyramidal neurons in a mouse model of autism. The European journal of neuroscience. 2022.

Although several observations suggest that the constitutive biological, genetic or physiological changes leading to Autism Spectrum Disorders (ASD) start in utero, their early impact on the number and density of neurons in the brain remains unknown. Using genetic fate mapping associated with the iDISCO clearing method we identified and counted a selective population of neocortical and hippocampal pyramidal neurons in the in utero valproate (VPA) mouse model of autism. We report that one day before birth the number of pyramidal neurons born at E14.5 in the neocortex and hippocampus of VPA-mice is smaller than in age-matched controls. VPA also induced a reduction of the neocortical -but not hippocampal- volume one day before birth. Interestingly, VPA-mice present an increase in both neocortical and hippocampal volumes 2 days after birth compared to controls. These results suggest that the VPA-exposed hippocampus and neocortex differ substantially from controls during the highly complex perinatal period, and specially one day before birth, reflecting the early pathogenesis of ASD.

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8. Genovesi E, Jakobsson C, Nugent L, Hanlon C, Hoekstra RA. Stakeholder experiences, attitudes and perspectives on inclusive education for children with developmental disabilities in sub-Saharan Africa: A systematic review of qualitative studies. Autism : the international journal of research and practice. 2022: 13623613221096208.

In sub-Saharan Africa, there are few services for children with developmental disabilities such as autism and intellectual disability. One way to support these children is to include them in mainstream schools. However, currently, African children with developmental disabilities are often excluded from mainstream education opportunities. People involved (e.g. teachers, families and children) can offer information on factors that could ease or interfere with inclusion. This article discusses the findings of published studies that explored the views of relevant groups on including children with developmental disabilities in mainstream schools in sub-Saharan Africa. We systematically searched the literature and identified 32 relevant articles from seven countries in sub-Saharan Africa. We found that unclear policies and insufficient training, resources and support for teachers often blocked the implementation of inclusive education. Factors in favour of inclusive education were the commitment of many teachers to include pupils with developmental disabilities and the work of non-governmental organisations (NGOs), which provided resources and training. This review suggests that motivated teachers should be provided with appropriate training, resources and support for inclusive education, directly and by promoting the work of NGOs.

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9. Gharehgazlou A, Vandewouw M, Ziolkowski J, Wong J, Crosbie J, Schachar R, Nicolson R, Georgiades S, Kelley E, Ayub M, Hammill C, Ameis SH, Taylor MJ, Lerch JP, Anagnostou E. Cortical Gyrification Morphology in ASD and ADHD: Implication for Further Similarities or Disorder-Specific Features?. Cerebral cortex (New York, NY : 1991). 2022; 32(11): 2332-42.

Shared etiological pathways are suggested in ASD and ADHD given high rates of comorbidity, phenotypic overlap and shared genetic susceptibility. Given the peak of cortical gyrification expansion and emergence of ASD and ADHD symptomology in early development, we investigated gyrification morphology in 539 children and adolescents (6-17 years of age) with ASD (n=197) and ADHD (n=96) compared to typically developing controls (n=246) using the local Gyrification Index (lGI) to provide insight into contributing etiopathological factors in these two disorders. We also examined IQ effects and functional implications of gyrification by exploring the relation between lGI and ASD and ADHD symptomatology beyond diagnosis. General Linear Models yielded no group differences in lGI, and across groups, we identified an age-related decrease of lGI and greater lGI in females compared to males. No diagnosis-by-age interactions were found. Accounting for IQ variability in the model (n=484) yielded similar results. No significant associations were found between lGI and social communication deficits, repetitive and restricted behaviours, inattention or adaptive functioning. By examining both disorders and controls using shared methodology, we found no evidence of atypicality in gyrification as measured by the lGI in these conditions.

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10. Guo D, Yang X, Gao M, Chen X, Tang Y, Shen L, Li K, Shi L. Deficiency of Autism-Related Gene Dock4 Leads to Impaired Spatial Memory and Hippocampal Function in Mice at Late Middle Age. Cellular and molecular neurobiology. 2022.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that lasts lifelong and causes noticeably higher premature mortality. Although the core symptoms and other behavioral deficits of ASD can persist or be deteriorated from early development to old age, how aging affects the behaviors and brain anatomy in ASD is largely unknown. DOCK4 is an ASD risk gene highly expressed in the hippocampus, and Dock4 knockout (KO) mice display ASD-like behaviors in adulthood (4- to 6-month-old). In this study, we evaluated the behavioral and hippocampal pathological changes of late-middle-aged (15- to 17-month-old) Dock4 male KO mice. Aged Dock4 KO mice continuously showed similar social deficit, elevated anxiety, and disrupted object location memory as observed in the adulthood, when compared to their wild-type (WT) littermates. Notably, Dock4 KO mice displayed an age-related decline of hippocampal dependent spatial memory, showing decreased spatial memory in Barnes maze than their WT littermates at late middle age. Morphological analysis from WT and Dock4 KO littermates revealed that Dock4 deficiency led to decreased mature neurons and oligodendrocytes but increased astrocytes in the hippocampus of late-middle-aged mice. Together, we report that ASD-like behaviors mostly persist into late-middle age in Dock4 KO mice, with specific alterations of spatial memory and hippocampal anatomy by age, thus providing new evidence for understanding age differences in behavioral deficits of ASD.

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11. Han GT, Trevisan DA, Abel EA, Cummings EM, Carlos C, Bagdasarov A, Kala S, Parker T, Canapari C, McPartland JC. Associations between sleep problems and domains relevant to daytime functioning and clinical symptomatology in autism: A meta-analysis. Autism research : official journal of the International Society for Autism Research. 2022.

Autistic individuals experience significantly higher rates of sleep problems compared to the general population, which negatively impacts various aspects of daytime functioning. The strength of associations across domains of functioning has not yet been summarized across studies. The present meta-analysis examined the strength of associations between sleep problems and various domains of daytime functioning in autistic individuals. Searches were conducted in EMBASE, PubMed, Web of Science, and Google Scholar through May 2020. Inclusion criteria were: an index of sleep disturbance in individuals diagnosed with autism spectrum disorder (ASD); data collected prior to any sleep-related intervention; statistical data indicating relations between sleep problems and outcomes relevant to behavior, cognition, and physical or mental health. Exclusion criteria were: statistics characterizing the relationship between sleep disturbance and outcome variables that partialled out covariates; studies examining correlations between different measures of sleep disturbance. Participants totaled 15,074 from 49 published articles and 51 samples, yielding 209 effect sizes. Sleep problems were significantly associated with more clinical symptomatology and worse daytime functioning. Subgroup analyses demonstrated that sleep problems were most strongly associated with internalizing and externalizing symptoms and executive functioning, followed by core autism symptoms, family factors, and adaptive functioning. Findings highlight the far-reaching consequences of sleep problems on daytime functioning for autistic individuals and support the continued prioritization of sleep as a target for intervention through integrated care models to improve wellbeing. LAY SUMMARY: Autistic individuals experience higher rates of sleep problems, such as difficulty falling asleep and staying asleep, compared to the general population. We quantitatively summarized the literature about how sleep problems are related to different aspects of daytime functioning to identify areas that may be most affected by sleep. Sleep problems were related to all areas assessed, with the strongest associations for mood and anxiety symptoms. We recommend prioritizing sleep health in autistic individuals to improve wellbeing and quality of life.

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12. McNeil R, Bray KK, Mitchell TV, Pendleton C, Marchini L. Are adults with autism receiving regular preventive dental services?. Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2022.

PURPOSE/AIM: To investigate the frequency of preventive dental care among adults with autism and explore factors associated with receiving regular preventive care. MATERIALS AND METHODS: De-identified data was collected from electronic health records of 18-year-old or older patients with autism that had at least one preventive dental procedure recorded. The data was then analyzed to describe the frequency of preventive dental procedures provided for this population and investigate what variables are associated with regular care. RESULTS: Sample size was 119, 67% were males, average age was 30.8 years, and 58% had Medicaid. Average BMI was 42.8, the prevalence of diabetes and heart disease were 16% and 34%, respectively, and 86% reported mental health problems. Recreational drug use was 6.8%, alcohol use was 19%, and tobacco use 16%. Xerostomia was reported by 32%, and the average number of medications was 7.2 ± 5.5. The average number of preventive dental visits was 7.9 ± 10.6, and 35% of the patients had at least one preventive dental visit per year. Only number of medications had a statistically significant association with number of preventive dental visits. CONCLUSIONS: Only one in every three adults with autism had at least one preventive dental visit per year.

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13. Mehra S, Ul Ahsan A, Seth E, Chopra M. Critical Evaluation of Valproic Acid-Induced Rodent Models of Autism: Current and Future Perspectives. Journal of molecular neuroscience : MN. 2022; 72(6): 1259-73.

Valproic acid (VPA) induced rodent model of autism is a widely accepted and extensively used rodent model to investigate the pharmacotherapy against autism. But, to date, its validation, suitability, and applicability as a well defining autistic model are still questionable. Previous research efforts highlighted that this model shows various core defining features of autism and related pathways, hence it is very necessary to explore its authenticity as a well-suited model for autism. Therefore, in this review, we summarize the preclinical and neurobiological relevant validated features, involved etiological mechanism, biological markers, treatment responses, drawbacks, current approaches, and future perspectives of VPA-induced model of autism. This review would help in deciphering the validation of the VPA-induced autistic model and its suitability as an experimental model of autism. A thorough investigation of behavioral, molecular, and neurobiological processes in animal models of autism would help in investigating the exact causation and effective treatment for autism.

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14. van Noorden LE, Sigafoos J, Waddington HL. Evaluating a Two-Tiered Parent Coaching Intervention for Young Autistic Children Using the Early Start Denver Model. Advances in neurodevelopmental disorders. 2022: 1-21.

OBJECTIVES: Early intervention can improve the outcomes of young autistic children, and parents may be well placed to deliver these interventions. The Early Start Denver Model (ESDM) is a naturalistic developmental behavioral intervention that can be implemented by parents with their own children (P-ESDM). This study evaluated a two-tiered P-ESDM intervention that used a group parent coaching program, and a 1:1 parent coaching program. We evaluated changes in parent use of the ESDM and parent stress, as well as child engagement, communication, and imitation. METHODS: Seven autistic or probably autistic children (< 60 months old) and their parents participated. A multiple-baseline design was used to compare individual changes between Baseline 1, Group Coaching (Tier 1), Baseline 2, and 1:1 Coaching (Tier 2). Parent and child behaviors were analyzed from weekly videos and graphed. Parenting stress was measured. RESULTS: All parents improved in their use of ESDM strategies after the Tier 1 intervention. Changes in parent fidelity during Tier 2 were mixed, but all parents maintained higher than baseline levels of fidelity. Six parents demonstrated above 75% ESDM fidelity in at least one session. There were positive changes in parent stress levels pre- post-intervention. Positive results were found for most children's levels of engagement, imitation, and communication. There were significant positive relationships between parent fidelity and both child engagement and child functional utterances. CONCLUSIONS: Group P-ESDM is a promising approach for improving parent fidelity and some child outcomes. Future randomized and controlled studies of group P-ESDM, using standardized outcome measures, are warranted. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41252-022-00264-8.

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