1. Austin C, Curtin P, Arora M, Reichenberg A, Curtin A, Iwai-Shimada M, Wright RO, Wright RJ, Remnelius KL, Isaksson J, Bölte S, Nakayama SF. Elemental Dynamics in Hair Accurately Predict Future Autism Spectrum Disorder Diagnosis: An International Multi-Center Study. Journal of clinical medicine. 2022; 11(23).

Autism spectrum disorder (ASD) is a neurodevelopmental condition diagnosed in approximately 2% of children. Reliance on the emergence of clinically observable behavioral patterns only delays the mean age of diagnosis to approximately 4 years. However, neural pathways critical to language and social functions develop during infancy, and current diagnostic protocols miss the age when therapy would be most effective. We developed non-invasive ASD biomarkers using mass spectrometry analyses of elemental metabolism in single hair strands, coupled with machine learning. We undertook a national prospective study in Japan, where hair samples were collected at 1 month and clinical diagnosis was undertaken at 4 years. Next, we analyzed a national sample of Swedish twins and, in our third study, participants from a specialist ASD center in the US. In a blinded analysis, a predictive algorithm detected ASD risk as early as 1 month with 96.4% sensitivity, 75.4% specificity, and 81.4% accuracy (n = 486; 175 cases). These findings emphasize that the dynamics in elemental metabolism are systemically dysregulated in autism, and these signatures can be detected and leveraged in hair samples to predict the emergence of ASD as early as 1 month of age.

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2. Bolognesi E, Guerini FR, Sotgiu S, Chiappedi M, Carta A, Mensi MM, Agliardi C, Zanzottera M, Clerici M. GC1f Vitamin D Binding Protein Isoform as a Marker of Severity in Autism Spectrum Disorders. Nutrients. 2022; 14(23).

Autism spectrum disorders (ASD) are characterized by a wide spectrum of clinical, behavioral, and cognitive manifestations. It is, therefore, crucial to investigate possible biomarkers associated with specific ASD phenotypes. Ample literature suggests a possible role for vitamin D (VD) in influencing ASD clinical phenotypes. We analyzed three vitamin D binding protein gene (DBP) functional polymorphisms (rs2282679, rs7041, and rs4588), which are involved in the modulation of vitamin D serum concentration in 309 ASD children and 831 healthy controls. Frequency comparisons of single nucleotide polymorphisms (SNPs) alleles, genotypes, and GC isoforms (GC1f, G1s, and GC2)-generated by the combination of rs7041 and rs4588 alleles-were correlated with ASD diagnostic, behavioral, and functioning scales. The GC1f isoform was significantly more frequent in ASD compared with controls (18.6% vs. 14.5% pc = 0.02). Significantly higher scores for item 15 of the Childhood Autism Rating Scale (CARS) and lower ones for the Children’s Global Assessment Scale (CGAS) functioning scales were seen in ASD carrying the GC1f isoform. In GC phenotype analysis, a gradient of severity for overall CARS scores and CARS item 15 was observed, with scores decreasing according to the presence of GC1f-GC1f > GC1f-GC1s > GC1s-GC1s > GC1f-GC2 > GC2-GC2 isoforms. Similarly, lower CGAS scores were seen in carriers of the GC1f-GC1f isoform, whereas higher scores were present in those carrying GC2-GC2 (p = 0.028). This is the first study to evaluate possible relationships between GC variants and the different aspects of ASD in Italian ASD children. Results, although needing to be validated in ampler cohorts, suggest that the GC1f isoform could be a marker of severity in ASD that may be useful in establishing the intensity of therapeutic and rehabilitative protocols.

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3. Boucher TQ, McIntyre CL, Iarocci G. Facilitators and Barriers to Physical Activity Involvement as Described by Autistic Youth with Mild Intellectual Disability. Advances in neurodevelopmental disorders. 2022: 1-13.

OBJECTIVES: Physical activity involvement among autistic youth and youth with an intellectual disability is significantly lower than the general population. Few studies have included youth with comorbid diagnoses of ASD and intellectual disability. Fewer studies collect information from the youth themselves. This study examined barriers and facilitators to physical activity in autistic youth with mild intellectual disability using semi-structured interviews with youth and through caregiver reports. METHODS: Fourteen caregivers and their children ages 8 to 16 years old participated. Caregivers completed a questionnaire about their thoughts on their child’s physical activity while their children completed the semi-structured interview. A descriptive phenomenological approach was followed. RESULTS: Four themes were inductively identified: intrapersonal barriers (factors that are within the person which impede physical activity involvement, such as exhibiting challenging behaviors that inhibit engagement), interpersonal barriers (factors external to the person, such as lack of community support), intrapersonal facilitators (factors within the person that enhance physical activity involvement, such as being intrinsically motivated to improve skills), and interpersonal facilitators (external factors such as supports from caregivers). CONCLUSIONS: Interviewing youth is important to capture a holistic picture of factors influencing physical activity. Future research may focus on implementing and assessing the efficacy of strategies to address the barriers facing youth diagnosed with ASD and intellectual disability. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41252-022-00310-5.

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4. Braga R, Felipe-Castaño E. The Impact of the COVID-19 Lockdown on the Cognitive Functions in Persons with Intellectual and Developmental Disabilities. International journal of environmental research and public health. 2022; 19(23).

The main objective of the research was to compare the cognitive functioning of a sample of persons with IDD (Intellectual and Developmental Disabilities) before the pandemic (2019) and after the pandemic (2020 and 2021), and to analyse the impact according to age and level of IDD impairment. The participants were 92 persons with IDD, of whom 43 were female (46.7%). The mean age in 2019 was 47.07 years (SD = 6.78). All the participants were living with family members. The CAMCOG-DS test from CAMDEX was used to assess the cognitive functions. The results indicate a worsening in cognitive functions (attention-concentration, abstract thought, language, and praxis) after lockdown, in both the total group of participants and the mild-moderate impairment group, and in both age groups. In the severely affected group, we found an improvement in the cognitive functions assessed after lockdown. These results are similar to those found in people with dementia and in the general ageing population. Results were discussed in relation to the consequences of isolation in people with IDD, as well as providing guidelines for future pandemic situations.

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5. Brisendine AE, O’Kelley SE, Sen B, Preskitt J, Wingate MS. Classifying children with ASD by service utilization and treatment type: A cluster analysis of a nationally representative United States survey. Acta psychologica. 2022; 232: 103800.

BACKGROUND: If there are patterns of the distribution of services and treatments across the population of people with ASD, these patterns should be based along clinical characteristics or other service needs and not sociodemographic characteristics unrelated to evidence-based care. We examined how individuals in a broad, nationally representative sample « grouped together » based on service utilization and services needed but not covered by insurance. By understanding various treatment patterns, clinicians, researchers, policymakers, and self-advocates and their families can better advocate for high-quality, evidence-based services to be provided equitably. METHODS: Using the 2011 Survey of Pathways to Diagnosis and Services, a cluster analysis was performed to explore patterns in this population based on medication use, private services use, school-based service use, and services not covered by insurance. Differences in clusters were then explored through multinomial logistic regression. RESULTS: Six clusters emerged, showing differences in the level of service/medication usage and insurance coverage. Differences across clusters were associated with the level of functional limitation and age at ASD diagnosis. Disparities by insurance type, functional limitation, and age at diagnosis exist among patterns of ASD service provision. CONCLUSIONS: Our analysis showed that intervention for children with ASD can be across several scales – high and low users of services (both private and school-based), high and low users of medications, and high and low levels of reported non-covered services. The differences were clustered in multiple ways. Further research should incorporate longitudinal and nationally representative data to explore these relationships further.

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6. Bufo MR, Guidotti M, Mofid Y, Malvy J, Bonnet-Brilhault F, Aguillon-Hernandez N, Wardak C. Atypical Response to Affective Touch in Children with Autism: Multi-Parametric Exploration of the Autonomic System. Journal of clinical medicine. 2022; 11(23).

This study aimed at evaluating the autonomic response to pleasant affective touch in children with Autism Spectrum Disorders (ASD) and age-matched typically developing (TD) peers, thanks to multiple autonomic nervous system (ANS) parameters and by contrasting CT (C-tactile fibers) high- vs. low-density territory stimulations. We measured pupil diameter, skin conductance, and heart rate during gentle stroking of two skin territories (CT high- and low-density, respectively, forearm and palm of the hand) in thirty 6-12-year-old TD children and twenty ASD children. TD children showed an increase in pupil diameter and skin conductance associated with a heart rate deceleration in response to tactile stimulations at the two locations. Only the pupil was influenced by the stimulated location, with a later dilation peak following CT low-density territory stimulation. Globally, ASD children exhibited reduced autonomic responses, as well as different ANS baseline values compared to TD children. These atypical ANS responses to pleasant touch in ASD children were not specific to CT-fiber stimulation. Overall, these results point towards both basal autonomic dysregulation and lower tactile autonomic evoked responses in ASD, possibly reflecting lower arousal and related to social disengagement.

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7. Carter Leno V, Pickard H, Cybulska L, Smith T, Munafo M, Penton-Voak I, Simonoff E, Pickles A, Bedford R. Associations between emotion recognition and autistic and callous-unemotional traits: differential effects of cueing to the eyes. Journal of child psychology and psychiatry, and allied disciplines. 2022.

BACKGROUND: Although autism and callous-unemotional (CU) traits are distinct conditions, both are associated with difficulties in emotion recognition. However, it is unknown whether the emotion recognition difficulties characteristic of autism and CU traits are driven by comparable underpinning mechanisms. METHODS: We tested whether cueing to the eyes improved emotion recognition in relation to autistic and CU traits in a heterogeneous sample of children enhanced for social, emotional and behavioural difficulties. Participants were 171 (n = 75 male) children aged 10-16 years with and without a diagnosis of autism (n = 99 autistic), who completed assessments of emotion recognition with and without cueing to the eyes. Parents completed the assessment of autistic and CU traits. RESULTS: Associations between autistic and CU traits and emotion recognition accuracy were dependent upon gaze cueing. CU traits were associated with an overall decrease in emotion recognition in the uncued condition, but better fear recognition when cued to the eyes. Conversely, autistic traits were associated with decreased emotion recognition in the cued condition only, and no interactions between autistic traits and emotion were found. CONCLUSIONS: The differential effect of cueing to the eyes in autistic and CU traits suggests different mechanisms underpin emotion recognition abilities. Results suggest interventions designed to promote looking to the eyes may be beneficial for children with CU traits, but not for children with autistic characteristics. Future developmental studies of autism and CU characteristics are required to better understand how different pathways lead to overlapping socio-cognitive profiles.

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8. Chen Y, Tang E, Ding H, Zhang Y. Auditory Pitch Perception in Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Journal of speech, language, and hearing research : JSLHR. 2022; 65(12): 4866-86.

PURPOSE: Pitch plays an important role in auditory perception of music and language. This study provides a systematic review with meta-analysis to investigate whether individuals with autism spectrum disorder (ASD) have enhanced pitch processing ability and to identify the potential factors associated with processing differences between ASD and neurotypicals. METHOD: We conducted a systematic search through six major electronic databases focusing on the studies that used nonspeech stimuli to provide a qualitative and quantitative assessment across existing studies on pitch perception in autism. We identified potential participant- and methodology-related moderators and conducted metaregression analyses using mixed-effects models. RESULTS: On the basis of 22 studies with a total of 464 participants with ASD, we obtained a small-to-medium positive effect size (g = 0.26) in support of enhanced pitch perception in ASD. Moreover, the mean age and nonverbal IQ of participants were found to significantly moderate the between-studies heterogeneity. CONCLUSIONS: Our study provides the first meta-analysis on auditory pitch perception in ASD and demonstrates the existence of different developmental trajectories between autistic individuals and neurotypicals. In addition to age, nonverbal ability is found to be a significant contributor to the lower level/local processing bias in ASD. We highlight the need for further investigation of pitch perception in ASD under challenging listening conditions. Future neurophysiological and brain imaging studies with a longitudinal design are also needed to better understand the underlying neural mechanisms of atypical pitch processing in ASD and to help guide auditory-based interventions for improving language and social functioning. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21614271.

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9. Cheung T, Ho YS, Fong KH, Lam YTJ, Li MH, Tse AC, Li CT, Cheng CP, Beisteiner R. Evaluating the Safety and Efficacy of Transcranial Pulse Stimulation on Autism Spectrum Disorder: A Double-Blinded, Randomized, Sham-Controlled Trial Protocol. International journal of environmental research and public health. 2022; 19(23).

Autistic spectrum disorder (ASD) is a common developmental disorder in children. The latest non-intrusive brain stimulation (NIBS) technology-transcranial pulse stimulation (TPS)-has been proven effective in older adults with mild neurocognitive disorders and adults with major depressive disorder. Nonetheless, there is so far no robust randomized controlled trial (RCT) conducted on adolescents with ASD nationwide. This study proposes a two-armed (verum TPS group vs. sham TPS group), double-blinded, randomized, sham-controlled trial. Both groups will be measured at four timepoints, namely, baseline (T1), 2 weeks immediately after post-TPS intervention (T2), and at the 1-month (T3) and 3-month (T4) follow-ups. Thirty-four subjects, aged between 12 and 17, diagnosed with ASD will be recruited in this study. All subjects will be computerized randomised into the verum TPS group or the sham TPS group on a 1:1 ratio. All subjects will undertake functional MRI (fMRI) before and after the 2-weeks TPS interventions, which will be completed in 2 weeks’ time. This will be the first RCT evaluating the efficacy of TPS adolescents with ASD in Hong Kong. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT05408793.

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10. Dedeoğlu Ö, Çetinkaya M, Emine Derinkuyu B, Aksoy E, Öztoprak Ü, Genç Sel Ç, Nursun Özcan H, Aksoy A, Yüksel D. Aspects of autism spectrum disorder and correlation with neuroimaging findings in tuberous sclerosis complex. Clinical neurology and neurosurgery. 2022; 224: 107550.

BACKGROUND: Tuberous sclerosis complex (TSC) patients may have different specific neuropsychological deficits related to the location of the tubers. Autism spectrum disorders (ASD) are common in TSC patients but the relationship between these diagnoses has not been formally explored. In this study we sought to examine brain Magnetic Resonance Imaging (MRI) findings in TSC patients with ASD. METHODS: We evaluated 34 TSC patients on the basis of DSM-V diagnostic criteria for ASD, Wechsler Intelligence Scale for Children (WISC-R), psychiatrist’s examination and also structured parent interviews. The number and localization of the tubers, postcontrast signal characteristics of the tubers, SWI findings, DWI findings on brain MRI were recorded. Demographic features, epilepsy histories, number of antiseizure medications, cognitive status were eveluated also. Patients were divided into two groups: ASD group, which represented group 1 and group 2 consisting of patients without any ASD symptoms. RESULTS: In our study, the mean number of tuber count was 21.8 in patients with ASD patients (Group 1, n = 13) and 12.4 in other TSC patients without ASD (Group 2, n = 21). Rate of tubers in prefrontal cortex/whole tubers (0.51) in patients with ASD was determined to be higher in group 1 (p = 0.003). Also a significant difference was detected between generalize epileptiform activities on EEG and the rate of DRE (p = 0.002; p = 0.001) between groups. Cognitive disturbances and infantile spasm history were similar between groups. TSC2 mutations have been identified in 29 (86%) patients. CONCLUSION: The mean of total tuber count and the rate of the location in the prefrontal cortex were determined to be higher in TSC patients with ASD. Specific areas on brain MRI may help understanding the development of ASD in TSC patients.

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11. Evans K, Whitehouse AJO, D’Arcy E, Hayden-Evans M, Wallace K, Kuzminski R, Thorpe R, Girdler S, Milbourn B, Bölte S, Chamberlain A. Perceived Support Needs of School-Aged Young People on the Autism Spectrum and Their Caregivers. International journal of environmental research and public health. 2022; 19(23).

With increasing demands for health, disability and education services, innovative approaches can help distribute limited resources according to need. Despite an increased focus on support needs within the clinical pathway and policy landscape, the body of research knowledge on this topic is at a relatively early stage. However, there appears to be a sense of unmet support needs and dissatisfaction with the provision of required support following an autism diagnosis amongst caregivers of young people on the spectrum. The primary aim of this study was to explore the perceived support needs of Australian school-aged young people on the spectrum and their caregiver(s). This was achieved using a phenomenographic Support Needs Interview conducted by occupational therapists during home-visits with caregivers of 68 young people on the spectrum (5-17 years). Qualitative data analysis resulted in two hierarchical outcome spaces, one each for young people and their caregivers, indicating interacting levels of support need areas that could be addressed through a combination of suggested supports. These support needs and suggested supports align with almost all chapters within the Body Functions, Activities and Participation and Environmental Factors domains of the International Classification of Functioning, Disability and Health. The overall goals of meeting these complex and interacting support needs were for the young people to optimize their functioning to reach their potential and for caregivers to ensure the sustainability of their caregiving capacity. A series of recommendations for support services, researchers and policy makers have been made to position support needs as central during the assessment, support and evaluation phases.

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12. Fontes-Dutra M, Marafiga JR, Santos-Terra J, Deckmann I, Schwingel GB, Rabelo B, de Moraes RK, Rockenbach M, Pasquetti MV, Gottfried C, Calcagnotto ME. GABAergic synaptic transmission and cortical oscillation patterns in the primary somatosensory area of a valproic acid rat model of autism spectrum disorder. The European journal of neuroscience. 2022.

Autism spectrum disorder (ASD) is characterized by impaired social communication and interaction associated with repetitive or stereotyped behavior. Prenatal valproic acid (VPA) exposure in rodents is a commonly used model of ASD. Resveratrol (RSV) has been shown to prevent interneuronal and behavioral impairments in the VPA model. We investigated the effects of prenatal VPA exposure and RSV on the GABAergic synaptic transmission, brain oscillations and on the genic expression of interneuron-associated transcription factor LHX6 in the primary somatosensory area (PSSA). Prenatal VPA exposure decreased the sIPSC and mIPSC frequencies and the sIPSC decay kinetics onto layers 4/5 pyramidal cells of PSSA. About 40% of VPA animals exhibited absence-like spike-wave discharge (SWD) events associated with behavior arrest and increased power spectrum density of delta, beta and gamma cortical oscillations. VPA animals had reduced LHX6 expression in PSSA but VPA animals treated with RSV had no changes on synaptic inhibition or LHX6 expression in the PSSA. SWD events associated with behavior arrest and the abnormal increment of cortical oscillations were also absent in in VPA animals treated with RSV. These findings provide new venues to investigate the role of both, RSV and VPA in the pathophysiology of ASD, and highlight the VPA animal model as an interesting tool to investigate pathways related to the etiology and possible future therapies to this neuropsychiatric disorder.

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13. Guo X, Tang P, Hou C, Li R. Mendelian randomization investigation highlights different roles of selenium status in mental disorders. Progress in neuro-psychopharmacology & biological psychiatry. 2023; 122: 110694.

Observational studies have suggested a relationship between selenium status and mental disorders (MDs). However, it remains unclear whether selenium status was causally associated with MDs. Thus, we performed a two-sample Mendelian randomization analysis using genome-wide association studies (GWAS) summary statistics to investigate the causal effects of selenium levels on seven MDs, including schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), bipolar disorder (BD), anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), and panic disorder (PD). Strong genetic instruments of blood selenium (n = 9) and blood-toenail selenium (n = 12) were applied to the above seven MDs GWAS datasets from Psychiatric Genomics Consortium, which were further replicated in the FinnGen Biobank. The inverse-variance weighted method was employed to calculate the causal effects. The results showed that genetically predicted blood selenium levels were associated with a decreased risk of schizophrenia (odds ratio [OR] = 0.90, 95% CI: 0.87-0.95) and AN (OR = 0.87, 95% CI: 0.77-0.97). However, both blood and blood-toenail selenium levels were linked to an increased risk of MDD (blood: OR = 1.08, 95% CI: 1.05-1.12; blood-toenail: OR = 1.08, 95% CI: 1.04-1.13) and ASD (blood: OR = 1.11, 95% CI: 1.05-1.17; blood-toenail: OR = 1.13, 95% CI: 1.05-1.21), respectively. No obvious associations were found between selenium levels and BD as well as ADHD. Our findings highlighted a protective role of selenium in SZ and AN, while a risk effect in MDD and ASD. Further studies are required to verify the underlying mechanism mediating the unequal effects of Se on different MDs, which will pave a new path for the intervention of MDs.

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14. Jiménez-Romero MS, Fernández-Urquiza M, Benítez-Burraco A. Language and Communication Deficits in Chromosome 16p11.2 Deletion Syndrome. Journal of speech, language, and hearing research : JSLHR. 2022; 65(12): 4724-40.

PURPOSE: Chromosome 16p11.2 deletion syndrome (OMIM #611913) is a rare genetic condition resulting from the partial deletion of approximately 35 genes located at Chromosome 16. Affected people exhibit a variable clinical profile, featuring mild dysmorphisms, motor problems, developmental delay, mild intellectual disability (ID), socialization deficits and/or autism spectrum disorder (ASD) traits, and problems with language. Specifically, a precise characterization of the speech, language, and communication (dis)abilities of people with this condition is still pending. METHOD: We used standardized tests and samples of naturalistic speech to provide a longitudinal profile of the speech, language, and communication problems of a boy with Chromosome 16p11.2 deletion syndrome and without ID or ASD. RESULTS: The proband shows impaired expressive abilities as well as problems with receptive language, dysprosody, and ASD-like communication deficits, such as impaired interactive skills, perseverative verbal behavior, overabundance of tangential responses, and lack of metapragmatic awareness and communicative use of gaze, meeting the criteria for social pragmatic communication disorder. CONCLUSIONS: Our results support the view that language and communication impairment should be regarded as one core symptom of Chromosome 16p11.2 deletion syndrome, even without a diagnosis of ASD or ID. Clinical implications of our results, with a focus on therapeutic interventions for children with 16p11.2 deletion syndrome and no ASD or ID, are also discussed. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21561714.

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15. Kim SY, Song DY, Bottema-Beutel K, Gillespie-Lynch K, Cage E. A systematic review and meta-analysis of associations between primarily non-autistic people’s characteristics and attitudes toward autistic people. Autism research : official journal of the International Society for Autism Research. 2022.

This systematic review includes a narrative synthesis and meta-analysis of research on the associations between primarily non-autistic people’s characteristics and their attitudes toward autistic people. Of 47 studies included in the narrative synthesis, White undergraduate students were surveyed most frequently. Demographic characteristics were the factors most frequently tested for associations with attitudes, followed by contact-related factors (i.e., quantity and quality), knowledge about autism, trait and personality factors, and other factors that did not fit into a single category. Internal consistency was not reported for some instruments assessing raters’ characteristics; some instruments had alpha levels lower than 0.70, and many characteristics of raters were measured using one-item measures. Moreover, theoretical motivations for investigating the raters’ characteristics were rarely provided. A total of 36 studies were included in the meta-analysis, which showed that attitudes toward autistic people were significantly associated with participants’ gender, knowledge about autism, and quality and quantity of their previous contact with autistic people, but not with their age or autistic traits. These findings indicate a need for more studies that focus on context-related characteristics (e.g., institutional variables such as support/commitment to inclusion), use reliable instruments to measure non-autistic people’s characteristics, and situate their investigation in a theoretical framework.

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16. Li Q, Shi Y, Li X, Yang Y, Zhang X, Xu L, Ma Z, Wang J, Fan L, Wu L. Proteomic-Based Approach Reveals the Involvement of Apolipoprotein A-I in Related Phenotypes of Autism Spectrum Disorder in the BTBR Mouse Model. International journal of molecular sciences. 2022; 23(23).

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Abnormal lipid metabolism has been suggested to contribute to its pathogenesis. Further exploration of its underlying biochemical mechanisms is needed. In a search for reliable biomarkers for the pathophysiology of ASD, hippocampal tissues from the ASD model BTBR T+ Itpr3tf/J (BTBR) mice and C57BL/6J mice were analyzed, using four-dimensional (4D) label-free proteomic analysis and bioinformatics analysis. Differentially expressed proteins were significantly enriched in lipid metabolic pathways. Among them, apolipoprotein A-I (ApoA-I) is a hub protein and its expression was significantly higher in the BTBR mice. The investigation of protein levels (using Western blotting) also confirmed this observation. Furthermore, expressions of SphK2 and S1P in the ApoA-I pathway both increased. Using the SphK inhibitor (SKI-II), ASD core phenotype and phenotype-related protein levels of P-CREB, P-CaMKII, and GAD1 were improved, as shown via behavioral and molecular biology experiments. Moreover, by using SKI-II, we found proteins related to the development and function of neuron synapses, including ERK, caspase-3, Bax, Bcl-2, CDK5 and KCNQ2 in BTBR mice, whose levels were restored to protein levels comparable to those in the controls. Elucidating the possible mechanism of ApoA-I in ASD-associated phenotypes will provide new ideas for studies on the etiology of ASD.

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17. Lin PC, Liang CS, Tsai CK, Tsai SJ, Chen TJ, Bai YM, Chen MH. Associations of a family history of lupus with the risks of lupus and major psychiatric disorders in first-degree relatives. QJM : monthly journal of the Association of Physicians. 2022; 115(12): 813-21.

BACKGROUND: Genetic factors link psychiatric disorders, particularly major depressive disorder (MDD), bipolar disorder, and obsessive-compulsive disorder (OCD), with systemic lupus erythematosus (SLE). Additionally, maternal SLE is a risk factor for long-term developmental problems, particularly learning disabilities, attention disorders, autism spectrum disorder (ASD) and speech disorders, in children. AIM: We aimed to determine whether first-degree relatives (FDRs) of patients with SLE have increased risks of SLE and major psychiatric disorders. DESIGN AND METHODS: Using the Taiwan National Health Insurance Research Database, we recruited 40 462 FDRs of patients with SLE as well as 161 848 matched controls. The risks of major psychiatric disorders, including schizophrenia, bipolar disorder, OCD, MDD, ASD and attention-deficit/hyperactivity disorder (ADHD), were assessed. RESULTS: The FDRs of patients with SLE had higher risks of SLE (reported as the adjusted relative risk and 95% confidence interval: 14.54; 12.19-17.34), MDD (1.23; 1.12-1.34), ADHD (1.60; 1.55-1.65), OCD (1.41; 1.14-1.74) and bipolar disorder (1.18; 1.01-1.38) compared with controls. Specifically, male FDRs of patients with SLE had higher risks of SLE and bipolar disorder, whereas female FDRs of patients with SLE had higher risks of MDD and OCD. Differences in the familial relationship (i.e. parents, children, siblings and twins) were consistently associated with higher risks of these disorders compared with controls. CONCLUSIONS: The FDRs of patients with SLE had higher risks of SLE, MDD, ADHD, OCD and bipolar disorder than the controls.

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18. Luo T, Chen SS, Ruan Y, Chen HY, Chen YM, Li YM, Zhou W. Downregulation of DDIT4 ameliorates abnormal behaviors in autism by inhibiting ferroptosis via the PI3K/Akt pathway. Biochemical and biophysical research communications. 2022; 641: 168-76.

Autism spectrum disorder (ASD) is a complex disease with unclear etiology. Studies have shown that ferroptosis is also related to ASD progression, but the specific mechanism is still unclear. Valproic acid (VPA) induced neuronal ferroptosis in vitro. Mechanistic studies showed that both VPA and ferroptosis inducers promoted the expression of DDIT4 in neurons, thereby inhibiting the activation of the PI3K/Akt pathway. DDIT4 increased the accumulation of ROS, MDA and Fe(2+), inhibited neuronal viability and downregulated GPX4 expression by inactivating the PI3K/Akt pathway. Ferroptosis inhibitors reversed the anti-survival effect of DDIT4, indicating that DDIT4 enhances ferroptosis through the PI3K/Akt pathway, thereby inhibiting neuronal viability. Further in vivo experiments found that autistic mice had high levels of ROS, MDA and Fe(2+), increased DDIT4 expression, and downregulated expression levels of GPX4, p-PI3K and p-Akt; after downregulation of DDIT4 expression, the accumulation of ROS, MDA and Fe(2+) was significantly reduced, while the expression levels of GPX4, p-PI3K and p-Akt were upregulated, indicating that DDIT4 knockdown reduces ferroptosis in autistic mice. In addition, DDIT4 downregulation, PI3K/Akt pathway activation, and ferroptosis inhibitors all improved social behavior deficits, repetitive stereotyped and compulsive behaviors, anxiety and exploratory behaviors in autistic mice, but PI3K/Akt pathway inhibitors significantly blocked the rescue of abnormal behaviors by DDIT4 downregulation in autistic mice. Therefore, downregulation of DDIT4 expression ameliorates abnormal behaviors in autism by inhibiting ferroptosis via the PI3K/Akt pathway, indicating that DDIT4, the PI3K/Akt pathway and ferroptosis have key roles in autism.

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19. McCarthy JM, Chaplin E. Adults with Intellectual Disability and Autism Spectrum Disorder: What Is the Evidence around the Use of Polypharmacy. International journal of environmental research and public health. 2022; 19(23).

A review on the mental health needs of adults with intellectual disability (ID) and autism spectrum disorder (ASD) published just over 10 years ago found a limited evidence base for pharmacological intervention in this group. The aim of this paper was therefore to review the evidence in the subsequent 10 years, with a focus on polypharmacy use in adults who have both ID and ASD. A critical literature review of key papers published from 2009 to 2021 was undertaken on adults with both ID and ASD and related to psychopharmacology, polypharmacy, antipsychotics, antidepressants, mood stabilisers and anxiolytics interventions in improving symptoms. After excluding articles for lack of relevance, a review with a focus on the use of polypharmacy was carried out on the retrieved results. Four papers were identified as relevant to adults with both ID and ASD. Three main themes were identified in the review, including the application of pharmacogenetics, the influence of national policy on prescribing practices and safety concerns in a population with multiple health comorbidities. The past decade has produced a small increase in the evidence base on psychopharmacology use in adults with ID and ASD. However, more evidence on the effectiveness and impact of long-term polypharmacy use is required.

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20. Pires G, Cruz A, Jesus D, Yasemin M, Nunes UJ, Sousa T, Castelo-Branco M. A new error-monitoring brain-computer interface based on reinforcement learning for people with autism spectrum disorders. Journal of neural engineering. 2022; 19(6).

Objective.Brain-computer interfaces (BCIs) are emerging as promising cognitive training tools in neurodevelopmental disorders, as they combine the advantages of traditional computerized interventions with real-time tailored feedback. We propose a gamified BCI based on non-volitional neurofeedback for cognitive training, aiming at reaching a neurorehabilitation tool for application in autism spectrum disorders (ASDs).Approach.The BCI consists of an emotional facial expression paradigm controlled by an intelligent agent that makes correct and wrong actions, while the user observes and judges the agent’s actions. The agent learns through reinforcement learning (RL) an optimal strategy if the participant generates error-related potentials (ErrPs) upon incorrect agent actions. We hypothesize that this training approach will allow not only the agent to learn but also the BCI user, by participating through implicit error scrutiny in the process of learning through operant conditioning, making it of particular interest for disorders where error monitoring processes are altered/compromised such as in ASD. In this paper, the main goal is to validate the whole methodological BCI approach and assess whether it is feasible enough to move on to clinical experiments. A control group of ten neurotypical participants and one participant with ASD tested the proposed BCI approach.Main results.We achieved an online balanced-accuracy in ErrPs detection of 81.6% and 77.1%, respectively for two different game modes. Additionally, all participants achieved an optimal RL strategy for the agent at least in one of the test sessions.Significance.The ErrP classification results and the possibility of successfully achieving an optimal learning strategy, show the feasibility of the proposed methodology, which allows to move towards clinical experimentation with ASD participants to assess the effectiveness of the approach as hypothesized.

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21. Singer A, Lutz A, Escher J, Halladay A. A full semantic toolbox is essential for autism research and practice to thrive. Autism research : official journal of the International Society for Autism Research. 2022.

Individuals diagnosed with autism spectrum disorder (ASD) present with a highly diverse set of challenges, disabilities, impairments and strengths. Recently, it has been suggested that researchers and practitioners avoid using certain words to describe the difficulties and impairments experienced by individuals with ASD to reduce stigma. The proposed limitations on terminology were developed by only a subset of the autism community, and the recommendations are already causing negative consequences that may be harmful to future scientific and clinical endeavors and, ultimately, to people with ASD. No one should have the power to censor language to exclude the observable realities of autism. Scientists and clinicians must be able to use any scientifically accurate terms necessary to describe the wide range of autistic people they study and support, without fear of censure or retribution.

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22. Vodakova E, Chatziioannou D, Jesina O, Kudlacek M. The Effect of Halliwick Method on Aquatic Skills of Children with Autism Spectrum Disorder. International journal of environmental research and public health. 2022; 19(23).

BACKGROUND: Swimming and the skills associated with participation in the aquatic environment tend to be an integral part of the movement literacy complex. Non-participation then affects the safety of movement in the aquatic environment and may also be the reason for the limitation of movement, psychological, and social development compared to peers. METHODS: This study is a single-subject research study. The aim of this study is to evaluate the effect of a seven-week intervention program of the Halliwick method in the development of aquatic skills, gross motor skills, and mental skills relevant for aquatic competence for children with autism spectrum disorder. Seven children with autism spectrum disorder participated in swimming classes for a two-week baseline period and a seven-week intervention program of the Halliwick method, one time per week. To measure the effect in the field of aquatic skills, we used the Alyn Water Orientation Test 1. To determine the level of gross motor skills, we used the Gross Motor Function Measure test. RESULTS: There was an improvement in aquatic skills and gross motor skills in seven participants; two of them did not improve in mental adjustment oriented to the breathing control sections in the water.

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23. Wang J, Liu Y, Huang HY, Wu JT, Wang WJ. [Influence of acupuncture on the clinical manifestations and gastrointestinal symptoms of children with autism spectrum disorder]. Zhongguo zhen jiu = Chinese acupuncture & moxibustion. 2022; 42(12): 1373-6.

OBJECTIVE: To observe the effect of acupuncture therapy based on « gut-brain axis » on clinical manifestations and gastrointestinal symptoms of children with autism spectrum disorder (ASD). METHODS: A total of 66 children with ASD were randomly divided into an observation group and a control group, 33 cases in each group. The control group was treated by routine rehabilitation training. On the basis of the control group, the observation group was treated with acupuncture based on « gut-brain axis », and the acupoints were Touwei (ST 8), Shenting (GV 24), Sishencong (EX-HN 1), Tianshu (ST 25), Zhongwan (CV 12), Zusanli (ST 36), etc. Both treatments were given once every other day, 3 times a week, 4 weeks as a course of treatment, consecutively for 3 courses. The scores of autism behavior checklist (ABC), TCM symptoms of gastrointestinal disease and childhood autism rating scale (CARS) were compared between the two groups before and after treatment, and the clinical efficacy was evaluated. RESULTS: After treatment, the scores of ABC, CARS and TCM symptoms of gastrointestinal disease in the two groups were lower than before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). The total effective rate of the observation group was 90.9% (30/33), which was higher than 81.8% (27/33) in the control group (P<0.05). CONCLUSION: On the basis of routine rehabilitation training, acupuncture therapy based on "gut-brain axis" is effective in treating ASD, which can relieve the clinical manifestations and gastrointestinal symptoms.

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24. Yang L, Lu S, Yang Z, Yao J, Zhou P, Zhao M. Generation of an induced pluripotent stem cell line (IPCASi001-A) from an autism spectrum disorder individual without intellectual disability. Stem cell research. 2022; 66: 102994.

Autism spectrum disorder (ASD) is a highly inheritable neurodevelopmental disorder that causes diverse deficits in social communication and restricted repetitive sensorimotor behaviors. Here, we studied a human-induced pluripotent cell line from an autistic patient with impaired social function and a normal intelligence quotient (IQ > 70). The cell line was validated by its morphology, gene expression, and potential to differentiate into three germ layers. This model can be used to explore the pathophysiological and molecular mechanisms in patients with ASD, compared those of with patients with normal cognitive abilities.

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25. Zhong T, Liu H, Li Y, Qi J. Correlates of Physical Activity of Children and Adolescents with Autism Spectrum Disorder in Low- and Middle-Income Countries: A Systematic Review of Cross-Sectional Studies. International journal of environmental research and public health. 2022; 19(23).

Children and adolescents with autism spectrum disorder (ASD) are at a high risk for a lack of physical activity (PA). The aim of this study is to review the evidence on the correlates of PA in children and adolescents with ASD in low- and middle-income countries. We searched Psychology and Behavioral Sciences Collection (PBSC), Scopus, PsycINFO, Web of Science (WOS), MEDLINE, Education Resources Information Center (ERIC), Education Source (ES), and Academic Search Premier (ASP) databases for relevant studies until April 2022, inclusive, to examine the factors associated with the studies of PA in children and adolescents with ASD aged 5 to 17 years in low- and middle-income countries. A total of 15 articles are included in the present review. Three researchers assessed the methodological quality and extracted relevant data of the included reviews. The correlates were synthesized and further assessed semi-quantitatively. Results of this review show that gender (boys) and more PA opportunities were positively associated with the PA of children and adolescents with ASD, while age and body mass index (BMI) were negatively related to their PA levels in low- and middle-income countries. The day of week was found to be inconsistently associated with PA in children and adolescents with ASD. The findings suggest that research on the correlates of PA in adolescents with ASD in low- and middle-income countries is limited. However, there are clear correlates for which future interventions could be based (age, gender, BMI, and PA opportunity) to promote PA participation in children and adolescents with ASD in low- and middle-income countries.

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