1. Avolio E, Olivito I, Rosina E, Romano L, Angelone T, De Bartolo A, Scimeca M, Bellizzi D, D’Aquila P, Passarino G, Alò R, Facciolo RM, Bagni C, De Lorenzo A, Canonaco M. Modifications of Behavior and Inflammation in Mice Following Transplant with Fecal Microbiota from Children with Autism. Neuroscience;2022 (Aug 21);498:174-189.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder displaying the modification of complex human behaviors, characterized by social interaction impairments, stereotypical/repetitive activities and emotional dysregulation. In this study, fecal microbiota transplant (FMT) via gavage from autistic children donors to mice, led to the colonization of ASD-like microbiota and autistic behaviors compared to the offspring of pregnant females exposed to valproic acid (VPA). Such variations seemed to be tightly associated with increased populations of Tenericutes plus a notable reduction (p < 0.001) of Actinobacteria and Candidatus S. in the gastrointestinal region of FMT mice as compared to controls. Indeed altered behaviors of FMT mice was reported when evaluated in the different maze tests (light dark, novel object, three chamber tests, novel cage test). Contextually, FMT accounted for elevated expression levels of the pro-inflammatory factors IL-1β, IL-6, COX-1 and TNF-α in both brain and small intestine. Villous atrophy and inflammatory infiltration (Caspase 3 and Ki67) were increased in the small intestine of FMT and VPA mice compared to controls. Moreover, the observed FMT-dependent alterations were linked to a decrease in the methylation status. Overall, findings of the present study corroborate a key role of gut microbiota in ASD. However, further investigations are required before any possible manipulation of gut bacteria with appropriate diets or probiotics can be conducted in ASD individuals.

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2. Blair N, Feingold J, Qian F, Weber-Gasparoni K. Comorbidities in Children with Autism Spectrum Disorder Undergoing Oral Rehabilitation Under General Anesthesia. J Dent Child (Chic);2022 (May 15);89(2):88-94.

Purpose:To investigate the oral health needs and comorbidities among patients with autism spectrum disorder (ASD) undergoing oral rehabilitation under general anesthesia (GA) at a university hospital.
Methods: Records of patients with ASD who underwent oral rehabilitation under GA between January 2016 and May 2019 were reviewed to identify comorbid conditions and oral health needs. Statistical analysis consisted of descriptive and bivariate analyses (alpha = 0.05).
Results:A total of 160 patients from three to 18 years of age fulfilled the inclusion criteria. Seventy-eight percent were male and 69 percent had public insurance. Be- havioral issues, such as anxiety, aggression and nonverbal status, were observed more frequently than reported in the ASD literature. Dental caries, poor oral hygiene and gingivitis were the most common dental conditions observed. Radiographs, sealants, stainless steel crowns and extractions were the most common treatments rendered. Bivariate analysis revealed that subjects who had eight to 15 comorbidities were likely to be older.
Conclusions: Patients with ASD have many dental needs and may have comorbid medical conditions that directly affect the safe delivery of GA and dental treatments. As patients with ASD age, the number of comorbidities increases.

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3. Gillett G, Leeves L, Patel A, Prisecaru A, Spain D, Happé F. The prevalence of autism spectrum disorder traits and diagnosis in adults and young people with personality disorders: A systematic review. Aust N Z J Psychiatry;2022 (Aug 19):48674221114603.

OBJECTIVES: Autism spectrum disorders and personality disorders are spectrum conditions with shared clinical features. Despite similarities, previous attempts to synthesise literature on co-existing prevalence and shared traits have employed a unidirectional focus, assessing personality characteristics of individuals with an autism spectrum disorder diagnosis. Here, we assess the prevalence of autism spectrum disorder diagnosis and/or traits among persons diagnosed with a personality disorder. METHODS: We systematically reviewed the English-language literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, according to a pre-registered protocol (PROSPERO: CRD 42021264106). Peer-reviewed quantitative studies reporting the prevalence of autism spectrum disorder diagnosis or traits in persons with an established personality disorder diagnosis were included. Studies were critically appraised using the Appraisal tool for Cross-Sectional Studies. RESULTS: Fifteen studies were identified, including 72,902 participants (median: 48, interquartile range: 30-77). Diagnoses included borderline, schizotypal and obsessive-compulsive personality disorders, and cohorts with unspecified personality disorder diagnoses. There was significant heterogeneity in diagnostic methodology and assessment tools used. We identified preliminary evidence of an increased prevalence of co-existing autism spectrum disorder diagnosis and traits among those diagnosed with a personality disorder, although significant limitations of the literature were identified. CONCLUSION: Our research suggests clinicians should consider conducting a careful developmental assessment when assessing service-users with possible or confirmed personality disorder. Future research directions may include larger studies featuring clinical control groups, an exploration of shared and differentiating behavioural-cognitive features of the two conditions, and investigation into potentially shared aetiological factors. Research investigating demographic factors that may contribute to potential diagnostic overshadowing would also be welcomed.

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4. Granato G, Borghi AM, Mattera A, Baldassarre G. A computational model of inner speech supporting flexible goal-directed behaviour in Autism. Sci Rep;2022 (Aug 20);12(1):14198.

Experimental and computational studies propose that inner speech boosts categorisation skills and executive functions, making human behaviour more focused and flexible. In addition, many clinical studies highlight a relationship between poor inner-speech and an executive impairment in autism spectrum condition (ASC), but contrasting findings are reported. Here we directly investigate the latter issue through a previously implemented and validated computational model of the Wisconsin Cards Sorting Tests. In particular, the model was applied to explore potential individual differences in cognitive flexibility and inner speech contribution in autistic and neurotypical participants. Our model predicts that the use of inner-speech could increase along the life-span of neurotypical participants but would be reduced in autistic ones. Although we found more attentional failures (i.e., wrong behavioural rule switches) in autistic children/teenagers and more perseverative behaviours in autistic young/older adults, only autistic children and older adults exhibited a lower performance (i.e., fewer consecutive correct rule switches) than matched control groups. Overall, our results corroborate the idea that the reduced use of inner speech could represent a disadvantage for autistic children and autistic older adults. Moreover, the results suggest that cognitive-behavioural therapies should focus on developing inner speech skills in autistic children as this could provide cognitive support throughout their whole life span.

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5. Iezzi D, Curti L, Ranieri G, Gerace E, Costa A, Ilari A, La Rocca A, Luceri C, D’Ambrosio M, Silvestri L, Scardigli M, Mannaioni G, Masi A. Acute rapamycin rescues the hyperexcitable phenotype of accumbal medium spiny neurons in the valproic acid rat model of autism spectrum disorder. Pharmacol Res;2022 (Sep);183:106401.

We previously demonstrated that prenatal exposure to valproic acid (VPA), an environmental model of autism spectrum disorder (ASD), leads to a hyperexcitable phenotype associated with downregulation of inward-rectifying potassium currents in nucleus accumbens (NAc) medium spiny neurons (MSNs) of adolescent rats. Aberrant mTOR pathway function has been associated with autistic-like phenotypes in multiple animal models, including gestational exposure to VPA. The purpose of this work was to probe the involvement of the mTOR pathway in VPA-induced alterations of striatal excitability. Adolescent male Wistar rats prenatally exposed to VPA were treated acutely with the mTOR inhibitor rapamycin and used for behavioral tests, ex vivo brain slice electrophysiology, single-neuron morphometric analysis, synaptic protein quantification and gene expression analysis in the NAc. We report that postnatal rapamycin ameliorates the social deficit and reverts the abnormal excitability, but not the inward-rectifying potassium current defect, of accumbal MSNs. Synaptic transmission and neuronal morphology were largely unaffected by prenatal VPA exposure or postnatal rapamycin treatment. Transcriptome analysis revealed extensive deregulation of genes implied in neurodevelopmental disorders and ionic mechanisms exerted by prenatal VPA, which was partially reverted by postnatal rapamycin. The results of this work support the existence of antagonistic interaction between mTOR and VPA-induced pathways on social behavior, neurophysiological phenotype and gene expression profile, thus prompting further investigation of the mTOR pathway in the quest for specific therapeutic targets in ASD.

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6. Li Y, Sun C, Guo Y, Qiu S, Liu Y, Zhong W, Wang H, Cheng Y. DIP2C polymorphisms are implicated in susceptibility and clinical phenotypes of autism spectrum disorder. Psychiatry Res;2022 (Oct);316:114792.

BACKGROUND: Disco-interacting protein 2 C (DIP2C) has recently been reported as a new susceptibility gene for autism spectrum disorder (ASD) in a genome-wide association study. METHODS: We evaluated associations between single nucleotide polymorphisms (SNPs) of DIP2C and ASD susceptibility in a case-control study (715 ASD cases and 728 controls) from Chinese Han. RESULTS: We identified a significant association between SNPs (rs3740304, rs2288681, rs7088729, rs4242757, rs10795060, and rs10904083) and ASD susceptibility. Of note, rs3740304, rs2288681, and rs7088729 are positively associated with ASD under inheritance models; moreover, haplotypes with any two marker SNPs (rs3740304 [G], rs2288681 [C], rs7088729 [T], rs4242757 [C], rs10795060 [G], and rs10904083 [A]) are also significantly associated with ASD. Additionally, rs10795060 and rs10904083 are associated with « visual reaction » phenotypes of ASD. CONCLUSIONS: DIP2C polymorphisms sort out the susceptibility and clinical phenotypes of autism spectrum disorder.

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7. Rosen V, Blank E, Lampert E, Dominick K, Will M, Erickson C, Pedapati E, Lamy M, Shaffer R. Brief Report: Telehealth Satisfaction Among Caregivers of Pediatric and Adult Psychology and Psychiatry Patients with Intellectual and Developmental Disability in the Wake of Covid-19. J Autism Dev Disord;2022 (Aug 20):1-13.

Telehealth has been shown to be both acceptable and effective in many areas of healthcare, yet it was not widely adopted prior to the SARS-CoV-2 (COVID-19) pandemic. Additionally, previous evaluations of telehealth for autism spectrum condition (ASC) and intellectual and developmental disability (IDD) populations are limited in both number and scope. Here, we investigated satisfaction amongst Psychology and Psychiatry patient caregivers at Cincinnati Children’s Hospital Medical Center (CCHMC) after the onset of the COVID-19 pandemic. Results (640 responses) showed high rates of satisfaction across departments, appointment types, and diagnoses, with 92% indicating overall satisfaction with their appointment. There were, however, notable decreases in satisfaction among Group Therapy respondents, and those whose diagnosis was classified as Other.

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8. Sato H, Fujita M, Tsuchiya A, Hatta T, Mori K, Nakazawa E, Takimoto Y, Akabayashi A. Disclosing a diagnosis of autism spectrum disorder without intellectual disability to pediatric patients in Japan in early diagnostic stages and associated factors: a cross-sectional study. Biopsychosoc Med;2022 (Aug 20);16(1):18.

With a recent increase in the prevalence of autism spectrum disorder (ASD), an important issue has emerged in clinical practice regarding when and how patients themselves should be given explanations following a diagnosis of ASD. The clinical guidelines of the UK National Institute for Health and Care Excellence state that children diagnosed with ASD should receive an explanation about what ASD is and how it affects their development and functioning-« if appropriate ». However, the guidelines do not provide any specifics regarding what constitutes « appropriate » situations METHODS: We conducted an anonymous self-administered postal questionnaire survey targeting all members of the Japanese Society for Child and Adolescent Psychiatry (n=1,995). The analysis included only physicians who had newly diagnosed pediatric patients with ASD in the past year. We imposed a limit of one year because diagnoses further back than that are difficult to recall; in other words, this would enhance the recall bias RESULTS: The recovery rate was 30.8%, and the rate of diagnosis disclosure to patients themselves without intellectual disability was 15.3%. We asked 361 physicians who responded that « deciding on a case-by-case basis » was the ideal way to disclose an ASD diagnosis about 20 items prioritized by physicians at the time of diagnosis disclosure and extracted three factors through exploratory factor analysis. Multiple logistic regression analysis was performed with physician attributes, awareness of ASD as a disorder or personality, and the three extracted factors as explanatory variables; diagnosis disclosure was the dependent variable. The patient age group and only one of the three factors (i.e., « factor related to readiness to accept diagnosis ») showed a significant association with disclosure of the diagnosis to the individual. Items included in the « factor related to readiness to accept diagnosis » were as follows: the degree of parental understanding, relationship of the patient with their parents/physician, agreement in opinion between parents, parental consent, « sufficient » patient understanding, symptom stabilization, and a guarantee of sufficient time required to explain the diagnosis to the patient CONCLUSION: In clinical settings, disclosing an ASD diagnosis with the consideration of patient/parent readiness toward accepting the diagnosis could help to guide physicians in determining an ideal timing for disclosure. Future studies are needed to establish detailed and concrete guidelines regarding disclosure of an ASD diagnosis to patients.

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9. Turnage D, Conner N. Quality of life of parents of children with Autism Spectrum Disorder: An integrative literature review. J Spec Pediatr Nurs;2022 (Aug 20):e12391.

PURPOSE: This paper presents an integrated literature review of the quality of life (QOL) in parents of individuals with Autism Spectrum Disorder (ASD). The rate of ASD is increasing. Parents of children with ASD have higher levels of stress and burden, which may lead to lower QOL. DESIGN AND METHODS: A comprehensive, electronic search was performed to retrieve 15 relevant articles, including 5565 participants. An integrative review was performed to appraise and synthesize findings. RESULTS: QOL was found to be lower in parents of children with ASD in physical, psychological, and social health and in spirituality, as compared with adults who were not parents of children with ASD. The strongest risk factor for parental QOL was the severity of the diagnosis of ASD. Protective factors for parental QOL were parent education level and levels of severity of ASD in the child. PRACTICE IMPLICATIONS: Nurses can support families impacted by ASD, particularly severe ASD, through tailored resources to support early diagnosis and intervention, through the support of policies affecting low-income families, and through increased awareness of severe ASD and its’ impact on the child and the family.

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10. Wang CG, Feng C, Zhou ZR, Cao WY, He DJ, Jiang ZL, Lin F. Imbalanced Gamma-band Functional Brain Networks of Autism Spectrum Disorders. Neuroscience;2022 (Aug 21);498:19-30.

Resting gamma-band brain networks are known as an inhibitory component in functional brain networks. Although autism spectrum disorder (ASD) is considered as with imbalanced brain networks, the inhibitory component remains not fully explored. The study reported 10 children with ASD and 10 typically-developing (TD) controls. The power spectral density analysis of the gamma-band signal in the cerebral cortex was performed at the source level. The normalized phase transfer entropy values (nPTEs) were calculated to construct brain connectivity. Gamma-band activity of the ASD group was lower than the TD children. The significantly inhibited brain regions were mainly distributed in the bilateral frontal and temporal lobes. Connectivity analysis showed alterations in the connections from key nodes of the social brain network. The behavior assessments in the ASD group revealed a significantly positive correlation between the total score of Childhood Autism Rating Scale and the regional nPTEs of the right transverse temporal gyrus. Our results provide strong evidence that the gamma-band brain networks of ASD children have a lower level of brain activities and different distribution of information flows. Clinical meanings of such imbalances of both activity and connectivity were also worthy of further explorations.

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11. Williams NJ, Hugh ML, Cooney DJ, Worley JA, Locke J. Testing a Theory of Implementation Leadership and Climate Across Autism Evidence-Based Interventions of Varying Complexity. Behav Ther;2022 (Sep);53(5):900-912.

Prominent theories within the field of implementation science contend that organizational leaders can improve providers’ fidelity to evidence-based practices (EBPs) by using focused implementation leadership behaviors that create an organizational climate for EBP implementation. However, this work has been criticized for overreliance on nonspecific, self-report fidelity measures and poor articulation of the boundary conditions that may attenuate leadership and climate’s influence. This study tests the predictions of EBP implementation leadership and climate theory on observed fidelity to three school-based EBPs for autism that vary in complexity: pivotal response training (PRT), discrete trial training (DTT), and visual schedules (VS). Educators in kindergarten to third-grade autism support classrooms in 65 schools assessed their principals’ EBP implementation leadership and school EBP implementation climate prior to the school year. Mid-school year, trained observers rated educator fidelity to all three interventions. Expert raters confirmed PRT was significantly more complex than DTT or VS using the Intervention Complexity Assessment Tool for Systematic Reviews. Linear regression analyses at the school level indicated principals’ increased frequency of EBP implementation leadership predicted a higher school EBP implementation climate, which in turn predicted higher educator fidelity to PRT-however, there was no evidence of a relationship between implementation climate and fidelity to DTT or VS. Comparing principals whose EBP implementation leadership was ±1 SD from the mean, there was a significant indirect association of EBP implementation leadership with PRT fidelity through EBP implementation climate (d = 0.49, 95% CI [0.04, 0.93]). Strategies that target EBP implementation leadership and climate may support fidelity to complex behavioral interventions.

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