1. Abubakar A, Gona JK, Kipkemoi P, Rimba K, Amukambwa D, Newton C. Perspectives of key stakeholders on educational experiences of children with autism spectrum disorders at the Kenyan Coast. African journal of disability. 2022; 11: 847.

BACKGROUND: Little is known about the educational experiences of children diagnosed with autism spectrum disorders (ASDs) in the Kenyan Coastal context. OBJECTIVES: We examined the diagnostic and placement procedures used in education on the Kenyan coastal region. In addition, we investigated the education-related challenges faced by children with ASD. METHODS: We conducted focus group discussions and in-depth interviews with 21 participants, including teachers, clinicians and educational administrators. Data were analysed using an inductive thematic framework on qualitative data analysis software, NVIVO 10. RESULTS: The findings from this study indicate that there were no systematic approaches to diagnosing children as having ASD. Teachers reported experiencing many challenges, including a lack of specialised training, inadequate resources and difficulty in managing children with different functional abilities in one class. CONCLUSION: There is an urgent need for contextually relevant evidence-based identification, placement and management services to be put in place to meet the educational needs of children with ASD.

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2. Badgett NM, Sadikova E, Menezes M, Mazurek MO. Emergency Department Utilization Among Youth with Autism Spectrum Disorder: Exploring the Role of Preventive Care, Medical Home, and Mental Health Access. Journal of autism and developmental disorders. 2022.

The 2016-2018 National Surveys of Children’s Health dataset was used to identify associations among preventive care, unmet health care needs, medical home access, and emergency department (ED) use among children and adolescents with autism spectrum disorder (ASD). Results indicated that youth with ASD had higher odds of using ED services if they had unmet mental health care needs (OR = 1.58, CI: 1.04-2.39) and lower odds of using ED services if they had access to a medical home (OR = 0.79, CI: 0.63-0.98). Findings suggest the importance of access to coordinated, comprehensive, and patient-centered care to address health care needs and prevent ED utilization among children and adolescents with ASD.

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3. Bied A, Njuguna S, Satodiya R. Autism in a Child With X-linked Agammaglobulinemia. Cureus. 2022; 14(2): e21951.

A growing evidence base has implicated immune dysfunction in the etiology of some cases of autism spectrum disorder. The precise relationship between immune disorders and autism spectrum disorder remains unclear. Herein we report a 14-year-old-male with agammaglobulinemia, who was diagnosed with autism spectrum disorder, and who has received exogenous immunoglobulins regularly for most of his life. This case study supports current theories implicating antibody deficiencies in some individuals with an autism spectrum disorder. Our case will add to the growing literature of understanding the connection between immune deficiencies in the pathogenesis of autism.

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4. Chen Y, Yan J, Jiang M, Zhang T, Zhao Z, Zhao W, Zheng J, Yao D, Zhang R, Kendrick KM, Jiang X. Adversarial Learning Based Node-Edge Graph Attention Networks for Autism Spectrum Disorder Identification. IEEE transactions on neural networks and learning systems. 2022; Pp.

Graph neural networks (GNNs) have received increasing interest in the medical imaging field given their powerful graph embedding ability to characterize the non-Euclidean structure of brain networks based on magnetic resonance imaging (MRI) data. However, previous studies are largely node-centralized and ignore edge features for graph classification tasks, resulting in moderate performance of graph classification accuracy. Moreover, the generalizability of GNN model is still far from satisfactory in brain disorder [e.g., autism spectrum disorder (ASD)] identification due to considerable individual differences in symptoms among patients as well as data heterogeneity among different sites. In order to address the above limitations, this study proposes a novel adversarial learning-based node-edge graph attention network (AL-NEGAT) for ASD identification based on multimodal MRI data. First, both node and edge features are modeled based on structural and functional MRI data to leverage complementary brain information and preserved in the constructed weighted adjacent matrix for individuals through the attention mechanism in the proposed NEGAT. Second, two AL methods are employed to improve the generalizability of NEGAT. Finally, a gradient-based saliency map strategy is utilized for model interpretation to identify important brain regions and connections contributing to the classification. Experimental results based on the public Autism Brain Imaging Data Exchange I (ABIDE I) data demonstrate that the proposed framework achieves a classification accuracy of 74.7% between ASD and typical developing (TD) groups based on 1007 subjects across 17 different sites and outperforms the state-of-the-art methods, indicating satisfying classification ability and generalizability of the proposed AL-NEGAT model. Our work provides a powerful tool for brain disorder identification.

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5. Chen YJ, Duku E, Georgiades S. Rethinking Autism Intervention Science: A Dynamic Perspective. Frontiers in psychiatry. 2022; 13: 827406.

Recent advances in longitudinal methodologies for observational studies have contributed to a better understanding of Autism as a neurodevelopmental condition characterized by within-person and between-person variability over time across behavioral domains. However, this finer-grained approach to the study of developmental variability has yet to be applied to Autism intervention science. The widely adopted experimental designs in the field-randomized control trials and quasi-experimental designs-hold value for inferring treatment effects; at the same time, they are limited in elucidating what works for whom, why, and when, given the idiosyncrasies of neurodevelopmental disorders where predictors and outcomes are often dynamic in nature. This perspective paper aims to serve as a primer for Autism intervention scientists to rethink the way we approach predictors of treatment response and treatment-related change using a dynamic lens. We discuss several empirical gaps, and potential methodological challenges and opportunities pertaining to: (1) capturing finer-grained treatment effects in specific behavioral domains as indexed by micro-level within-person changes during and beyond intervention; and (2) examining and modeling dynamic prediction of treatment response. Addressing these issues can contribute to enhanced study designs and methodologies that generate evidence to inform the development of more personalized interventions and stepped care approaches for individuals on the heterogeneous spectrum of Autism with changing needs across development.

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6. Cooper K, Mandy W, Russell A, Butler C. Healthcare clinician perspectives on the intersection of autism and gender dysphoria. Autism : the international journal of research and practice. 2022: 13623613221080315.

Autistic people are more likely to have a gender identity which does not match their sex assigned at birth. Some people experience distress about their sex and gender not matching, which is called gender dysphoria. Such individuals may wish to attend a gender clinic to access healthcare support for gender dysphoria. Currently, there is limited evidence to help clinicians best support autistic people who need healthcare for gender dysphoria. We wanted to find out what healthcare clinicians think about working with autistic patients with gender dysphoria. We interviewed 16 clinicians who work in healthcare services with adults and young people who are autistic and experience gender dysphoria. We recorded the interviews and carefully analysed the content to find key themes. We found that clinicians worked with patients to try and better understand their experiences of gender dysphoria. Clinicians identified features of autism that they believed were related to gender identity and dysphoria including different thinking styles, social differences, and sensory sensitivities. Clinicians noticed that autistic people spoke about their gender in different ways to non-autistic people. Clinicians tried to adapt their practice to better meet the needs of their autistic patients. These adaptations tended to focus on differences in the assessment process, for example, offering longer or shorter appointments and changing their communication style. We conclude that clinicians were offering an individualised approach to autistic patients experiencing gender dysphoria. However, these clinicians were particularly interested in working with autistic people, and so may not be representative of the wider clinician population. Clinicians working in this area should receive training on autism adaptations and the intersection of autism and gender dysphoria.

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7. Finch TL, Mackintosh J, Petrou A, McConachie H, Le Couteur A, Garland D, Parr JR. « We couldn’t think in the box if we tried. We can’t even find the damn box »: A qualitative study of the lived experiences of autistic adults and relatives of autistic adults. PloS one. 2022; 17(3): e0264932.

Autistic children grow to become autistic adults, and autism is increasingly diagnosed in adulthood and later life. This qualitative study aimed to understand experiences of autism throughout adulthood. A national cohort study of autistic adults and relatives of autistic adults (ASC-UK), enabled purposive recruitment of a diverse sample. Semi-structured interviews were conducted with 29 autistic adults (aged 20-71 years), mostly diagnosed in adulthood, and 16 relatives (aged 31-81 years) of autistic adults diagnosed across both childhood and adulthood (including some with learning disability). Interview topics included health, relationships, education, employment, quality of life and everyday experiences. Thematic analysis of the accounts of the autistic adults identified six key themes relating to their experiences: (1) diagnosis as validating yet limiting; (2) supportive and non-supportive social agents; (3) the « invisibility » of the needs of autistic adults; (4) health in the context of autism; (5) staying ‘outside’ the circle; and (6) multiple lives with autism. Data from relatives about autistic adult experiences gave additional perspectives on these themes. Experiences reported in other studies-of ‘difference’ from others, challenges of social engagement, and learning to ‘conform’ to society’s expectations-were evident and relevant to male and female autistic adults, across all age groups, and unrelated to stage of life when diagnosed. Some expressed disappointment with their lives, but others were proud of their achievements. Education and employment, whilst challenging for many, were also rewarding for some. Health care and social services were often experienced as inaccessible, inappropriate, or lacking understanding of the individual’s needs. We conclude that greater public understanding of autism as experienced in adulthood is needed. Key priorities are improving the availability of ‘appropriate’ health and social care services for autistic adults and families, and providing practical support to enable enhanced participation in life.

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8. Guma E, Bordeleau M, González Ibáñez F, Picard K, Snook E, Desrosiers-Grégoire G, Spring S, Lerch JP, Nieman BJ, Devenyi GA, Tremblay ME, Chakravarty MM. Differential effects of early or late exposure to prenatal maternal immune activation on mouse embryonic neurodevelopment. Proceedings of the National Academy of Sciences of the United States of America. 2022; 119(12): e2114545119.

SignificancePrenatal exposure to maternal infection increases the risk of developing mental health disorders, such as schizophrenia and autism spectrum disorder. Exposure to maternal immune activation has been associated with a number of neuroanatomical deficits in adolescent and adult offspring, with differing effects based on the gestational timing of infection. However, little is known about how the embryo brain is affected. We show, using whole-brain MRI, that maternal immune activation significantly affects brain anatomy. When the exposure occurs early in pregnancy, volume reductions are mainly observed, while the opposite is true for exposure later in pregnancy. Furthermore, we identify alterations to the density of certain classes of neurons and glia, which have been associated with stress and inflammation in the brain.

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9. He X, Xie J, Zhang J, Wang X, Jia X, Yin H, Qiu Z, Yang Z, Chen J, Ji Z, Yu W, Chen M, Xu W, Gao H. Acid-Responsive Dual-Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum Disorder. Advanced science (Weinheim, Baden-Wurttemberg, Germany). 2022: e2104286.

The treatment of autism spectrum disorder (ASD) is one of the most difficult challenges in neurodevelopmental diseases, because of the unclear pathogenesis research and low brain-lesion targeting efficiency. Besides, maternal immune activation has been reported as the most mature and widely used model of ASD and aspirin-triggered lipoxin A4 is a potent anti-inflammatory mediator being involved in the resolution of neuroinflammation in ASD. Therefore, an aspirin encapsulated cascade drug delivery system (Asp@TMNPs) is established, which can successively target the blood-brain barrier (BBB) and microglial cells and response to the acid microenvironment in lysosome. As a result, the mitochondrial oxidative stress, DNA damage, and inflammation of microglial cells are prominently alleviated. After the treatment of Asp@TMNPs, the social interaction, stereotype behavior, and anxious condition of ASD mice are notably improved and the activation of microglial cells is inhibited. Overall, this system successively penetrates the BBB and targets microglial cells, therefore, it significantly enhances the intracephalic drug accumulation and improves anti-neuroinflammatory efficacy of aspirin, providing a promising strategy for ASD treatment.

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10. Kong Y, Li QB, Yuan ZH, Jiang XF, Zhang GQ, Cheng N, Dang N. Multimodal Neuroimaging in Rett Syndrome With MECP2 Mutation. Frontiers in neurology. 2022; 13: 838206.

Rett syndrome (RTT) is a rare neurodevelopmental disorder characterized by severe cognitive, social, and physical impairments resulting from de novo mutations in the X-chromosomal methyl-CpG binding protein gene 2 (MECP2). While there is still no cure for RTT, exploring up-to date neurofunctional diagnostic markers, discovering new potential therapeutic targets, and searching for novel drug efficacy evaluation indicators are fundamental. Multiple neuroimaging studies on brain structure and function have been carried out in RTT-linked gene mutation carriers to unravel disease-specific imaging features and explore genotype-phenotype associations. Here, we reviewed the neuroimaging literature on this disorder. MRI morphologic studies have shown global atrophy of gray matter (GM) and white matter (WM) and regional variations in brain maturation. Diffusion tensor imaging (DTI) studies have demonstrated reduced fractional anisotropy (FA) in left peripheral WM areas, left major WM tracts, and cingulum bilaterally, and WM microstructural/network topology changes have been further found to be correlated with behavioral abnormalities in RTT. Cerebral blood perfusion imaging studies using single-photon emission CT (SPECT) or PET have evidenced a decreased global cerebral blood flow (CBF), particularly in prefrontal and temporoparietal areas, while magnetic resonance spectroscopy (MRS) and PET studies have contributed to unraveling metabolic alterations in patients with RTT. The results obtained from the available reports confirm that multimodal neuroimaging can provide new insights into a complex interplay between genes, neurotransmitter pathway abnormalities, disease-related behaviors, and clinical severity. However, common limitations related to the available studies include small sample sizes and hypothesis-based and region-specific approaches. We, therefore, conclude that this field is still in its early development phase and that multimodal/multisequence studies with improved post-processing technologies as well as combined PET-MRI approaches are urgently needed to further explore RTT brain alterations.

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11. Luo Z, Qi Q, Wang K, Zhou J, Chen S, Wang L. Current status of and challenges posed by autism spectrum disorders in China: Prevalence, legal issues, and public awareness. Bioscience trends. 2022.

Over the past 30 years or so, the body of research on autism spectrum disorders (ASD) in China has grown steadily. With the tireless efforts of government agencies and private organizations, the legitimate rights and interests of children with ASD have been initially guaranteed through a series of education and rehabilitation reforms, yet there are still many challenges to overcome. Many quality studies on the prevalence of ASD have been conducted in recent years, but China has lacked official census data until now. Moreover, there is a general lack of awareness of ASD even among the groups that directly interact with individuals with ASD, namely parents/caregivers, teachers, and doctors. Despite that fact, ASD should be brought to the attention of professionals and policymakers so that they can take appropriate measures, which include i) early comprehensive screening and diagnosis of ASD, ii) improvement of the corresponding policies and regulatory system, and iii) promotion of public awareness of ASD.

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12. Mamah D, Mutiso V, Gitonga I, Tele A, Ndetei DM. A population-based survey of autistic traits in Kenyan adolescents and young adults. The South African journal of psychiatry : SAJP : the journal of the Society of Psychiatrists of South Africa. 2022; 28: 1694.

BACKGROUND: To date, there have been no large-scale population studies of autistic traits (AUT) conducted in Africa. AIM: The study aimed to estimate the prevalence and characteristics of autism spectrum disorders in a large sample of Kenyan adolescents and young adults. SETTING: Tertiary academic institutions (87%) and directly from the community (13%). METHODS: Our study surveyed 8918 youths (aged 15-25 years) using the autism spectrum quotient (AQ). Based on AQ scores, we derived groups with low (L-AUT), borderline (B-AUT), and high (H-AUT) autistic traits. Relationships of AUT with demographic factors, psychosis, affectivity and stress were investigated. RESULTS: Internal consistency of the AQ in the population was excellent (Cronbach’s α = 0.91). Across all participants, 0.63% were estimated as having H-AUT, while 14.9% had B-AUT. Amongst community youth, prevalence of H-AUT was 0.98%. Compared to those with low and borderline traits, H-AUT participants were more likely to be males, to have lower personal and parental educational attainment, and to be of a lower socioeconomic status. The H-AUT group also had higher psychotic and affective symptoms as well as higher psychosocial stress than other groups. CONCLUSION: The prevalence of H-AUT amongst Kenyan youth is comparable to Autism spectrum disorder (ASD) rates in many countries. Autistic traits in Kenya are associated with worse social and clinical profiles. Further research on autism across Africa is needed to investigate cross-cultural heterogeneity of this disorder, and to guide healthcare policy.

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13. Olivé G, Slušná D, Vaquero L, Muchart-López J, Rodríguez-Fornells A, Hinzen W. Structural connectivity in ventral language pathways characterizes non-verbal autism. Brain structure & function. 2022.

Language capacities in autism spectrum disorders (ASD) range from normal scores on standardized language tests to absence of functional language in a substantial minority of 30% of individuals with ASD. Due to practical difficulties of scanning at this severe end of the spectrum, insights from MRI are scarce. Here we used manual deterministic tractography to investigate, for the first time, the integrity of the core white matter tracts defining the language connectivity network in non-verbal ASD (nvASD): the three segments of the arcuate (AF), the inferior fronto-occipital (IFOF), the inferior longitudinal (ILF) and the uncinate (UF) fasciculi, and the frontal aslant tract (FAT). A multiple case series of nine individuals with nvASD were compared to matched individuals with verbal ASD (vASD) and typical development (TD). Bonferroni-corrected repeated measure ANOVAs were performed separately for each tract-Hemisphere (2:Left/Right) × Group (3:TD/vASD/nvASD). Main results revealed (i) a main effect of group consisting in a reduction in fractional anisotropy (FA) in the IFOF in nvASD relative to TD; (ii) a main effect of group revealing lower values of radial diffusivity (RD) in the long segment of the AF in nvASD compared to vASD group; and (iii) a reduced volume in the left hemisphere of the UF when compared to the right, in the vASD group only. These results do not replicate volumetric differences of the dorsal language route previously observed in nvASD, and instead point to a disruption of the ventral language pathway, in line with semantic deficits observed behaviourally in this group.

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14. Papadopoulos N, Sciberras E, Hiscock H, Williams K, McGillivray J, Mihalopoulos C, Engel L, Fuller-Tyszkiewicz M, Bellows ST, Marks D, Howlin P, Rinehart N. Sleeping Sound Autism Spectrum Disorder (ASD): a randomised controlled trial of a brief behavioural sleep intervention in primary school-aged autistic children. Journal of child psychology and psychiatry, and allied disciplines. 2022.

BACKGROUND: Behavioural sleep problems are common in children with autism spectrum disorder (ASD); however, evidence for the efficacy of behavioural sleep interventions is limited. This study examined the efficacy of a brief behavioural sleep intervention in autistic children. It was hypothesised that the intervention would reduce overall child sleep problems (primary outcome), in addition to improvements in children’s social, emotional, cognitive, academic functioning, and quality of life, and parent/caregivers’ stress, quality of life, and mental health (secondary outcomes). METHODS: A randomised controlled trial was conducted with participants randomised via a computer-generated sequence to the sleeping sound intervention (n = 123) or treatment as usual (n = 122) group. Participants comprised 245 children with an ASD diagnosis. Inclusion criteria were as follows: confirmation of DSM IV or DSM-5 diagnosis of ASD, participants aged between 5 and 13 years and parent/caregiver report of moderate-severe sleep problems. Exclusion criteria were as follows: parent/caregiver intellectual disability or lacking sufficient English to complete questionnaires; and child participant with co-occurring medical conditions known to impact sleep. The intervention group received the sleeping sound intervention (2 × 50-min face-to-face sessions plus follow-up phone call) by a trained clinician. RESULTS: Change in children’s sleep problems was measured by the Children’s Sleep Habits Questionnaire (CSHQ) at 3 months post randomisation. Parents/caregivers of children in the intervention group reported a reduction in child sleep problems at 3 months post randomisation (effect size: E.S -0.7). There were also small effects in a number of child (internalising symptoms, emotional behavioural disturbance and quality of life) and parent/caregiver (mental health, parenting stress and quality of life) outcomes; however, these did not remain significant when controlling for multiple comparisons. CONCLUSIONS: The sleeping sound ASD intervention is an efficacious and practical way to reduce sleep problems for autistic children. This brief behavioural intervention has the potential to be embedded easily into the Australian healthcare system.

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15. Proteau-Lemieux M, Knoth IS, Agbogba K, Côté V, Barlahan Biag HM, Thurman AJ, Martin CO, Bélanger AM, Rosenfelt C, Tassone F, Abbeduto LJ, Jacquemont S, Hagerman R, Bolduc F, Hessl D, Schneider A, Lippé S. Corrigendum: EEG Signal Complexity Is Reduced During Resting-State in Fragile X Syndrome. Frontiers in psychiatry. 2022; 13: 867000.

[This corrects the article DOI: 10.3389/fpsyt.2021.716707.].

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16. Raj R, Owen D, Kannan L, Syeda U. Polypharmacy in a Patient With Intellectual and Developmental Disabilities. Cureus. 2022; 14(2): e22019.

Prader-Willi syndrome (PWS) is an uncommon condition and its clinical manifestation in adulthood includes central obesity, hypogonadism, osteoporosis, cardiovascular disease, diabetes mellitus, and sleep apnea. These patients often have mild to moderate intellectual disability and are dependent upon their caregiver for healthcare needs. Hence, they may be at increased risk of polypharmacy-related complications, if there is poor communication between healthcare providers and caregivers. We present a case of a 26-year-old adult with PWS and mild to moderate intellectual disability, who was found to have acute kidney injury resulting from drug interaction between multiple nephrotoxic medications. Our case report highlights the importance of continuity of care with primary care providers, especially in patients with intellectual and developmental disabilities (IDD).

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17. Schiavi S, La Rosa P, Petrillo S, Carbone E, D’Amico J, Piemonte F, Trezza V. N-Acetylcysteine Mitigates Social Dysfunction in a Rat Model of Autism Normalizing Glutathione Imbalance and the Altered Expression of Genes Related to Synaptic Function in Specific Brain Areas. Frontiers in psychiatry. 2022; 13: 851679.

Prenatal exposure to valproic acid (VPA) is a risk factor for autism spectrum disorder (ASD) in humans and it induces autistic-like behaviors in rodents. Imbalances between GABAergic and glutamatergic neurotransmission and increased oxidative stress together with altered glutathione (GSH) metabolism have been hypothesized to play a role in both VPA-induced embriotoxicity and in human ASD. N-acetylcysteine (NAC) is an antioxidant precursor of glutathione and a modulator of glutamatergic neurotransmission that has been tested in ASD, although the clinical studies currently available provided controversial results. Here, we explored the effects of repeated NAC (150 mg/kg) administration on core autistic-like features and altered brain GSH metabolism in the VPA (500 mg/kg) rat model of ASD. Furthermore, we measured the mRNA expression of genes encoding for scaffolding and transcription regulation proteins, as well as the subunits of NMDA and AMPA receptors and metabotropic glutamate receptors mGLUR1 and mGLUR5 in brain areas that are relevant to ASD. NAC administration ameliorated the social deficit displayed by VPA-exposed rats in the three-chamber test, but not their stereotypic behavior in the hole board test. Furthermore, NAC normalized the altered GSH levels displayed by these animals in the hippocampus and nucleus accumbens, and it partially rescued the altered expression of post-synaptic terminal network genes found in VPA-exposed rats, such as NR2a, MGLUR5, GLUR1, and GLUR2 in nucleus accumbens, and CAMK2, NR1, and GLUR2 in cerebellum. These data indicate that NAC treatment selectively mitigates the social dysfunction displayed by VPA-exposed rats normalizing GSH imbalance and reestablishing the expression of genes related to synaptic function in a brain region-specific manner. Taken together, these data contribute to clarify the behavioral impact of NAC in ASD and the molecular mechanisms that underlie its effects.

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18. Silverman JL, Thurm A, Ethridge SB, Soller MM, Petkova SP, Abel T, Bauman MD, Brodkin ES, Harony-Nicolas H, Wöhr M, Halladay A. Reconsidering animal models used to study autism spectrum disorder: Current state and optimizing future. Genes, brain, and behavior. 2022: e12803.

Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and intellectual disability (ID), are pervasive, often lifelong disorders, lacking evidence-based interventions for core symptoms. With no established biological markers, diagnoses are defined by behavioral criteria. Thus, preclinical in vivo animal models of NDDs must be optimally utilized. For this reason, experts in the field of behavioral neuroscience convened a workshop with the goals of reviewing current behavioral studies, reports, and assessments in rodent models. Goals included: (a) identifying the maximal utility and limitations of behavior in animal models with construct validity; (b) providing recommendations for phenotyping animal models; and (c) guidelines on how in vivo models should be used and reported reliably and rigorously while acknowledging their limitations. We concluded by recommending minimal criteria for reporting in manuscripts going forward. The workshop elucidated a consensus of potential solutions to several problems, including revisiting claims made about animal model links to ASD (and related conditions). Specific conclusions included: mice (or other rodent or preclinical models) are models of the neurodevelopmental insult, not specifically any disorder (e.g., ASD); a model that perfectly recapitulates a disorder such as ASD is untenable; and greater attention needs be given to validation of behavioral testing methods, data analysis, and critical interpretation.

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19. Tang S, Liu X, Ran Q, Nie L, Wu L, Pan Z, He L. Application of Three-Dimensional Pseudocontinuous Arterial Spin Labeling Perfusion Imaging in the Brains of Children With Autism. Frontiers in neurology. 2022; 13: 851430.

OBJECTIVE: To explore the application of three-dimensional pseudocontinuous arterial spin labeling (3D-PCASL) perfusion imaging in the brains of children with autism and to understand the characteristics of cerebral blood perfusion in children with autism. METHODS: A total of 320 children with autism (160 men and 160 women) aged between 2 and 18 years and 320 age- and sex-matched healthy children participated in the study. All children were scanned by 3.0 T magnetic resonance axial T1 fluid-attenuated inversion recovery (FLAIR), T2 FLAIR, 3D-T1, and 3D-PCASL sequences. After postprocessing, cerebral blood flow (CBF) values in each brain region of children with autism and healthy children at the same age were compared and analyzed. Furthermore, CBF characteristics in each brain region of autistic children at various ages were determined. RESULTS: The CBF values of the frontal lobe, hippocampus, temporal lobe, and caudate nucleus of children with autism are lower than those of healthy children (P < 0.05). Additionally, as the ages of children with autism increase, the number of brain regions with decreased CBF values gradually increases. A receiver operating characteristic (ROC) analysis results show that the CBF values of the frontal lobe, hippocampus, temporal lobe, and caudate nucleus can distinguish children with autism [area under the ROC curve (AUC) > 0.05, P < 0.05]. CONCLUSION: The 3D-PCASL shows lower brain CBF values in children with autism. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier: ChiCTR2000034356.

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20. Uljarević M, Bott NT, Libove RA, Phillips JM, Parker KJ, Hardan AY. Characterizing Emotion Recognition and Theory of Mind Performance Profiles in Unaffected Siblings of Autistic Children. Frontiers in psychology. 2021; 12: 736324.

Emotion recognition skills and the ability to understand the mental states of others are crucial for normal social functioning. Conversely, delays and impairments in these processes can have a profound impact on capability to engage in, maintain, and effectively regulate social interactions. Therefore, this study aimed to compare the performance of 42 autistic children (Mage = 8.25 years, SD = 2.22), 45 unaffected siblings (Mage = 8.65 years, SD = 2.40), and 41 typically developing (TD) controls (Mage = 8.56 years, SD = 2.35) on the Affect Recognition (AR) and Theory of Mind (TOM) subtests of the Developmental Neuropsychological Assessment Battery. There were no significant differences between siblings and TD controls. Autistic children showed significantly poorer performance on AR when compared to TD controls and on TOM when compared to both TD controls and unaffected siblings. An additional comparison of ASD, unaffected sibling and TD control subsamples, matched on full-scale IQ, revealed no group differences for either AR or TOM. AR and TOM processes have received less research attention in siblings of autistic children and remain less well characterized. Therefore, despite limitations, findings reported here contribute to our growing understanding of AR and TOM abilities in siblings of autistic children and highlight important future research directions.

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21. Vellingiri B, Aishwarya SY, Benita Jancy S, Sriram Abhishek G, Winster Suresh Babu H, Vijayakumar P, Narayanasamy A, Mariappan S, Sangeetha R, Valsala Gopalakrishnan A, Parthasarathi R, Iyer M. An anxious relationship between Autism Spectrum Disorder and Gut Microbiota: A tangled chemistry?. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2022; 99: 169-89.

Autism spectrum disorder (ASD) is a serious multifactorial neurodevelopmental disorder often accompanied by strained social communication, repetitive behaviour, immune dysregulation, and gastrointestinal (GI) issues. Recent studies have recorded a link between dysbiosis in the gut microbiota (gm) and the primary stages of ASD. A bidirectional connection (also called microbiota-gut-brain-axis) exchanges information between the gut bacteria and central nervous system. When the homeostasis of the microenvironment of the gut is dysregulated, it causes oxidative stress, affecting neuronal cells and neurotransmitters, thereby causing neurodevelopmental disorders. Studies have confirmed a difference in the constitution of gut bacteria among ASD cases and their controls. Numerous studies on animal models of ASD have shown altered gm and its association with abnormal metabolite profile and altered behaviour phenotype. This process happens due to an abnormal metabolite production in gm, leading to changes in the immune system, especially in ASD. Hence, this review aims to question the current knowledge on gm dysbiosis and its related GI discomforts and ASD behavioural symptoms and shed light on the possible therapeutic approaches available to deal with this situation. Thereby, though it is understood that more research might be needed to prove an association or causal relationship between gm and ASD, therapy with the microbiome may also be considered as an effective strategy to combat this issue.

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22. Wang K, Qi Q, Luo Z, Zhou J, Chen S, Wang L. Autism spectrum disorder: Status of primary care in China. Bioscience trends. 2022.

Primary care serves as the cornerstone to ensure positive health outcomes for diseases. Autism spectrum disorder (ASD) has attracted more attention as a lifelong neurodevelopmental disorder with a prevalence that is increasing yearly. Although the demand for primary care for ASD is rapidly expanding, there are many challenges that need to be faced. Here, the current status of primary care for ASD in China is described. i) Identification of and care for ASD includes pre-diagnosis, diagnosis and evaluation, and treatment; the complexity of the disease and the lack of public understanding increase delays in diagnosis and treatment. ii) Most instruments, which are indispensable for diagnosing and evaluating ASD, are of foreign origin. iii) Treatments for ASD are based on mainstream Western interventions with complementary approaches. iv) The scale of rehabilitation and educational institutions has gradually grown and their expertise has gradually increased but rehabilitation costs are relatively high.

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23. Welch V, Wy TJ, Ligezka A, Hassett LC, Croarkin PE, Athreya AP, Romanowicz M. Use of Mobile and Wearable Artificial Intelligence in Child and Adolescent Psychiatry: Scoping Review. Journal of medical Internet research. 2022; 24(3): e33560.

BACKGROUND: Mental health disorders are a leading cause of medical disabilities across an individual’s lifespan. This burden is particularly substantial in children and adolescents because of challenges in diagnosis and the lack of precision medicine approaches. However, the widespread adoption of wearable devices (eg, smart watches) that are conducive for artificial intelligence applications to remotely diagnose and manage psychiatric disorders in children and adolescents is promising. OBJECTIVE: This study aims to conduct a scoping review to study, characterize, and identify areas of innovations with wearable devices that can augment current in-person physician assessments to individualize diagnosis and management of psychiatric disorders in child and adolescent psychiatry. METHODS: This scoping review used information from the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of several databases from 2011 to June 25, 2021, limited to the English language and excluding animal studies, was conducted. The databases included Ovid MEDLINE and Epub ahead of print, in-process and other nonindexed citations, and daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; Web of Science; and Scopus. RESULTS: The initial search yielded 344 articles, from which 19 (5.5%) articles were left on the final source list for this scoping review. Articles were divided into three main groups as follows: studies with the main focus on autism spectrum disorder, attention-deficit/hyperactivity disorder, and internalizing disorders such as anxiety disorders. Most of the studies used either cardio-fitness chest straps with electrocardiogram sensors or wrist-worn biosensors, such as watches by Fitbit. Both allowed passive data collection of the physiological signals. CONCLUSIONS: Our scoping review found a large heterogeneity of methods and findings in artificial intelligence studies in child psychiatry. Overall, the largest gap identified in this scoping review is the lack of randomized controlled trials, as most studies available were pilot studies and feasibility trials.

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24. Wickberg F, Lenhard F, Aspvall K, Serlachius E, Andrén P, Johansson F, Silverberg-Mörse M, Mataix-Cols D. Feasibility of internet-delivered cognitive-behavior therapy for obsessive-compulsive disorder in youth with autism spectrum disorder: A clinical benchmark study. Internet interventions. 2022; 28: 100520.

Obsessive-compulsive disorder (OCD) is a treatable condition that often requires specialist care, particularly when comorbid with autism spectrum disorder (ASD). However, specialist clinics are few and typically located in large medical centers. To increase availability of evidence-based treatment for OCD in individuals with ASD, we adapted an internet-delivered cognitive behavior therapy (ICBT) protocol to suit the needs of these individuals and conducted a feasibility study (N = 22). The primary outcome was the clinician-rated Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), administered at pre- and post-treatment as well as 3 months after treatment. ICBT was deemed acceptable and was associated with clinically significant improvements in CY-BOCS scores, corresponding to a large within-group effect size (Cohen’s d = 1.33). Similarly, significant improvements were observed in most of the secondary parent- and self-rated measures. Approximately 60% of the participants were classed as treatment responders and 50% were in remission from their OCD at the 3-month follow-up. To provide a meaningful benchmark, we also analyzed data from a specialist clinic that regularly treats individuals with comorbid OCD and ASD (N = 52). These analyses indicated that specialized in-person CBT produced significantly larger effects (d = 2.69) while being markedly more resource demanding, compared to ICBT. To conclude, ICBT can be successfully adapted to treat OCD in youth with ASD and may be a viable alternative for those who do not have direct access to highly specialized treatment. Further improvements of the treatment protocol based on participant and therapist feedback are warranted, as is a formal test of its efficacy and cost-effectiveness in a randomized controlled trial.

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25. Winder-Patel B, Tudor ME, Kerns CM, Davis K, Nordahl CW, Amaral DG, Solomon M. Often Undiagnosed but Treatable: Case Vignettes and Clinical Considerations for Assessing Anxiety Disorders in Youth with Autism Spectrum Disorder and Intellectual Disability. Evidence-based practice in child and adolescent mental health. 2022; 7(1): 24-40.

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26. Yang N, Hurd PL, Crespi BJ. Why iPlay: The Relationships of Autistic and Schizotypal Traits With Patterns of Video Game Use. Frontiers in psychology. 2022; 13: 767446.

Video games are popular and ubiquitous aspects of human culture, but their relationships to psychological and neurophysiological traits have yet to be analyzed in social-evolutionary frameworks. We examined the relationships of video game usage, motivations, and preferences with autistic and schizotypal traits and two aspects of neurophysiology, reaction time and targeting time. Participants completed the Autism Quotient, Schizotypal Personality Questionnaire, a Video Game Usage Questionnaire, and two neurophysiological tasks. We tested in particular the hypotheses, motivated by theory and previous work, that: (1) participants with higher autism scores would play video games more, and participants with higher schizotypy scores would play video games less; and (2) autism and positive schizotypy would be associated with opposite patterns of video game use, preferences and motivations. Females, but not males, with higher autism scores played more video games, and exhibited evidence of relatively male-typical video game genre preferences and motivations. By contrast, positive schizotypy was associated with reduced video game use in both genders, for several measures of game use frequency. In line with previous findings, males played video game more than females did overall, preferred action video games, and exhibited faster reaction and targeting times. Females preferred Puzzle and Social Simulation games. Faster reaction and targeting times were associated with gaming motives related to skill development and building behavior. These findings show that gaming use and patterns reflect aspects of psychology, and gender, related to social cognition and imagination, as well as aspects of neurophysiology. More generally, the results suggest that video game use is notably affected by levels of autistic and schizotypal traits, and that video games may provide an evolutionarily novel medium for imaginative play in which immersive play experiences can be decoupled from social interaction.

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27. Zisapel N. Assessing the potential for drug interactions and long term safety of melatonin for the treatment of insomnia in children with autism spectrum disorder. Expert review of clinical pharmacology. 2022; 15(2): 175-85.

INTRODUCTION: Melatonin preparations are emerging first-line pharmacotherapy for insomnia in children and adolescents with autism spectrum disorder (ASD), but quality, formulation, consistency, dosing, and limited long-term safety data are of concern. The recent approval of pediatric-appropriate prolonged-release melatonin (Ped-PRM) addresses these aspects. AREAS COVERED: A systematic search of PubMed and web of science for prospective, randomized, and controlled trials (RCTs) of melatonin preparations vs placebo in children and adolescents with ASD and the European public assessment report on Ped-PRM was conducted. EXPERT OPINION: Melatonin is rapidly absorbed and undergoes first pass hepatic metabolism by cytochrome CYP1A2; over 80% is excreted in the urine as 6-sulfatoxymelatonin (inactive). Immediate-release melatonin (IRM) is short-acting (3-4 h), whereas PRM provides therapeutic levels throughout the night. Drugs interacting with CYP1A2 are likely to slow-down melatonin metabolism. High variability in bioavailability among subjects calls for dose optimization. Melatonin was essentially safe for short-term use (up to 3 months). Long-term data available for Ped-PRM demonstrate fatigue (6.3%), somnolence (6.3%), and mood swings (4.2%) with no evidence of effects on height, BMI, or pubertal development, tolerance or withdrawal effects following long-term use of this product. Studies on long-term safety of IRM and oversight of melatonin supplement manufacture are warranted.

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