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Increased risks associated with Coronavirus disease 2019 (COVID-19) among individuals with autism spectrum disorder (ASD) combined with previous reports of heightened vaccine hesitancy among parents of children with ASD indicate the need for a better understanding of attitudes and behaviors related to COVID-19 vaccines among the ASD community. This study is the first to our knowledge to use a mixed-methods approach to understand attitudes toward COVID-19 vaccines among parents of children with ASD and autistic adults. Participants were 135 members of the ASD community residing in the state of Arizona (99 parents of children with ASD and 36 autistic adults) who responded to the third (Spring 2021) and fourth (Summer 2021) time points of a larger longitudinal online survey. Quantitative findings indicated that autistic adults had slightly more favorable attitudes toward COVID-19 vaccines than parents, and attitudes in both subsamples became more positive over time. However, both parents and autistic adults reported COVID-19 vaccine uptake that was consistent with or better than the general population at both time points. Thematic analysis of responses to open-ended questions identified five themes that characterized factors that contributed to participants' decisions about COVID-19 vaccinations, including: (1) Desiring a Return to Normalcy, (2) Protection of Self and Others, (3) Previous Experience with COVID-19 (4) Science and Medical Professionals,and (5) Skepticism Regarding Safety, Effectiveness, and Need. Current findings combined with emerging literature paint a relatively optimistic picture about COVID-19 vaccine acceptance in the ASD community., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The male preponderance in autism spectrum disorder (ASD) led to the hypothesis that aspects of female biology are protective against ASD. Females with ASD (ASD-F) report more compensatory behaviors (i.e. "camouflaging") to overcome ASD-related social differences, which may be a mechanism of protection. No studies have examined sex-related brain pathways supporting camouflaging in ASD-F, despite its potential to inform mechanisms underlying the ASD sex bias. We used functional connectivity (FC) to investigate "sex-atypical" and "sex-typical" FC patterns linked to camouflaging in adults with ASD and examined multimodal coherence of findings via structural connectometry. Exploratory associations with cognitive/emotional functioning examined the adaptive nature of FC patterns. We found (i) "sex-atypical" FC patterns linked to camouflaging in the hypothalamus and precuneus and (ii) "sex-typical" patterns in the right anterior cingulate and anterior parahippocampus. Higher hypothalamic FC with a limbic reward cluster also correlated with better cognitive control/emotion recognition. Structural connectometry validated FC results with consistent brain pathways/effect patterns implicated in ASD-F. In summary, "male-typical" and "female-typical" brain connectivity patterns support camouflaging in ASD-F in circuits implicated in reward, emotion, and memory retrieval. "Sex-atypical" results are consistent with fetal steroidogenic/neuroinflammatory hypotheses. However, female genetics/biology may contribute to "female-typical" patterns implicated in camouflaging., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: The unprecedented challenges introduced by the Coronavirus disease 2019 (COVID-19) pandemic may be amplified for children with autism spectrum disorder (ASD) and their families., Aims: The current study aimed to describe the experiences of children with ASD and their families during the pandemic and to identify the needs of this community during emergency situations., Methods and Procedures: Participants were 122 parents of 122 children and adolescents (aged 3-18 years; one parent per family participated) with ASD living in Arizona, USA who participated in the first time point (July/August 2020) of a larger longitudinal survey study. A qualitative approach based in grounded theory methodology was used to analyze six open-ended survey questions., Outcomes and Results: The resulting conceptual model included a core category, Longing for Stability, and four main categories: Public Health Measures Yielding New Challenges and Unexpected Gains, Experiencing Abrupt Changes across Developmental Domains, Changing Family Dynamics, and Protective Factors., Conclusions: Findings add to limited research examining whether, and how, emergency events uniquely impact the ASD community, identifying potential methods by which services can be proactively adapted to best support the needs of children with ASD., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study examined the feasibility and acceptability of a telehealth diagnostic model deployed at an autism center in the southwestern United States to safely provide autism spectrum disorder (ASD) diagnostic evaluations to children, adolescents, and adults during the COVID-19 pandemic. Participants included all clients for whom a telehealth diagnostic evaluation was scheduled at the diagnostic clinic (n = 121) over a 6-month period. Of 121 scheduled clients, 102 (84%) completed the telehealth evaluation. A diagnostic determination was made for 91% of clients (93 out of 102) using only telehealth procedures. Nine participants (two females; ages 3 to 11 years) required an in-person evaluation. Responses from psychologist and parent acceptability surveys indicated the model was acceptable for most clients. Psychologist ratings suggested that telehealth modalities used in the current study may be less acceptable for evaluating school-aged children with subtle presentations compared to children in the early developmental period, adolescents, and adults. Parents of females reported higher acceptability than parents of males. Findings contribute to the small but growing literature on feasibility and acceptability of telehealth evaluations for ASD and have implications for improving access to care during and after the COVID-19 pandemic. LAY SUMMARY: This study described telehealth methods for evaluating children, adolescents, and adults for autism spectrum disorder. Telehealth methods were generally acceptable to psychologists conducting the evaluations and parents of diagnostic clients. Psychologists reported the methods to be less acceptable for school-aged children and parents of males found the methods less acceptable than parents of females. The telehealth methods described may help to increase access to diagnostic professionals and reduce wait times for evaluations during and after the COVID-19 pandemic., (© 2021 International Society for Autism Research and Wiley Periodicals LLC.)

Lay Abstract: Adaptive functioning describes the age-appropriate skills necessary for independent living. Research suggests that autistic children, adolescents, and adults who do not have an intellectual disability demonstrate adaptive functioning challenges relative to their intellectual ability. Thus, even though many of these individuals have the intellectual capacity to excel in mainstream educational and vocational settings, their adaptive functioning challenges may serve as an obstacle to independence. The research on adaptive functioning in autistic adults is focused on statistical analysis of standardized assessments (e.g. parent-report on multiple choice questionnaires). Qualitative research that examines the narratives of young adults and their parents is needed to better understand adaptive functioning in young adults and their resulting service needs. This study combined statistical analysis of standardized assessments with qualitative analysis of interview responses from autistic young adults without intellectual disability and their parents. Findings replicated previous reports of adaptive functioning challenges and identified influences on adaptive functioning development, consequences of independence, and service needs. Taken together, findings indicate the need for interventions and services that facilitate adaptive functioning development in autistic adolescents and young adults and provide insight into potential intervention targets and strategies.

The authors carried out a factor analysis of the Yale-Brown Obsessive-Compulsive Scale checklist at the category level in order to reduce the number of variables in this domain and ultimately identify possible endophenotypes; 181 children with autism were enrolled. The authors estimated a tetrachoric correlation matrix among the dichotomous symptom categories and then used exploratory and confirmatory factor analyses to identify a clinically meaningful factor structure for this correlation matrix. Their analysis supported a four-factor solution: obsessions, higher-order repetitive behaviors, lower-order repetitive behaviors, and hoarding. These findings are another step in the effort to identify genetically and biologically distinct groups within this population.

This study was conducted to examine the relationship between whole blood serotonin level and behavioral symptoms in 78 subjects with autism. No significant associations were found between serotonin level and the primary behavioral outcome measures. However, a significant inverse relationship between serotonin level and self-injury was demonstrated., (2009 Elsevier Ltd. All rights reserved.)

The male-to-female (M:F) ratio for autism spectrum disorders (ASD), typically about 4:1, appears to decrease with increasing paternal age, but this relationship has not been systematically tested. With 393 ASD cases from families with two or more ASD cases, we categorized paternal age into five age groups (<30, 30-34, 35-39, 40-44, 45+) and found that the M:F ratio was significantly decreased with increasing paternal age groups and remained so after also adjusting for maternal age. No significant relationship between maternal age group and the M:F ratio was observed. This study suggests that the M:F ratio is reduced with increasing paternal age consistent with de novo genetic or genomic anomalies arising more frequently as men age and then conceive children.

Background: Clinical heterogeneity of autism likely hinders efforts to find genes associated with this complex psychiatric disorder. Some studies have produced promising results by restricting the sample according to the expression of specific familial factors or components of autism. Previous factor analyses of the restricted, repetitive behaviors and interest (RRBI) domain of autism have consistently identified a two-factor model that explains a moderate amount of variance. The identification of additional factors may explain more variance in the RRBI domain and provide an additional component of autism that may help in the identification of underlying genetic association., Methods: We conducted factor analyses of RRBI symptoms with a sample that included verbal subjects meeting full criteria for autism aged 5 to 22 years (n = 245). Among affected sibling pairs (n = 126) we examined the familial aggregation of the identified factors. We also examined the associations of the factors with autism-related personality traits in fathers and mothers (n = 50)., Results: The previously identified two-factor model - insistence on sameness (IS) and repetitive stereotypic motor behaviors (RSMB) - was replicated in our sample. Next, a second factor analysis that included the item for verbal rituals resulted in a four-factor model - IS, 'simple' RSMB, 'complex' RSMB, and a fourth factor including symptoms associated with intense preoccupations (IP). Of these four, both IS and IP were significantly familial among affected siblings, but only IP was significantly correlated with the broader autism phenotype traits of rigidity and aloofness in fathers., Conclusions: The results support previous evidence for the IS factor, its familiality, and the identification of IP as an additional strong candidate trait for genetic studies of autism.

Evidence for a genetic association between autism and two single nucleotide polymorphisms (SNPs), rs2056202 and rs2292813, in the mitochondrial aspartate/glutamate carrier (SLC25A12) gene led us to ask whether any of the four previously identified familial traits in autism spectrum disorders (ASD) varied by these SNPs. In 355 ASD cases from 170 sibships we examined levels of the four traits in these SNPs using ANCOVA models. The primary models selected unrelated affected cases and used age and sex as covariates. An ancillary set of models used all affected siblings and included "sibship" as a random effects independent variable. We found significantly lower levels of routines and rituals associated with the presence of the less frequent A allele in rs2056206. No other significant differences were observed. The rs2056202 polymorphism may be associated with levels of routines and rituals in autism and related disorders., (Copyright 2007 Wiley-Liss, Inc.)

Mutations in the PTEN gene are associated with a broad spectrum of disorders, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Lhermitte-Duclos disease. In addition, PTEN mutations have been described in a few patients with autism spectrum disorders (ASDs) and macrocephaly. In this study, we screened the PTEN gene for mutations and deletions in 88 patients with ASDs and macrocephaly (defined as >or=2 SD above the mean). Mutation analysis was performed by direct sequencing of all exons and flanking regions, as well as the promoter region. Dosage analysis of PTEN was carried out using multiplex ligation-dependent probe amplification (MLPA). No partial or whole gene deletions were observed. We identified a de novo missense mutation (D326N) in a highly conserved amino acid in a 5-year-old boy with autism, mental retardation, language delay, extreme macrocephaly (+9.6 SD) and polydactyly of both feet. Polydactyly has previously been described in two patients with Lhermitte-Duclos disease and CS and is thus likely to be a rare sign of PTEN mutations. Our findings suggest that PTEN mutations are a relatively infrequent cause of ASDs with macrocephaly. Screening of PTEN mutations is warranted in patients with autism and pronounced macrocephaly, even in the absence of other features of PTEN-related tumor syndromes., ((c) 2007 Wiley-Liss, Inc.)

The TPH1 and TPH2 genes encode the rate-limiting enzymes that control serotonin biosynthesis, and serotonin is clearly altered in autism. In the current study, eight SNPs in the TPH1 gene region and eight SNPs within the TPH2 gene were examined by family-based association tests in a large cohort of 352 families with autism and in clinically defined subsets of these families with either severe obsessive-compulsive behaviors (sOCB) or self-stimulatory behaviors (SSB). We found no evidence for association between autism and single SNPs or haplotypes of the TPH1 and TPH2 genes in the cohort of all families or in the sOCB and SSB subsets. In particular, we failed to replicate the association between autism and variants of the TPH2 gene, rs4341581 (TRANSMIT P = 1; PDT P = 0.323; FBAT P = 0.446) and rs11179000 (TRANSMIT P = 0.174; PDT P = 0.293; FBAT P = 0.374). Furthermore, no evidence for linkage was observed between autism and SNPs in the TPH1 and TPH2 genes (although linkage at the TPH2 locus was observed in the SSB subset). Thus, it appears unlikely that the TPH1 and TPH2 genes play a significant role in the susceptibility to autism or to autism endophenotypes including sOCB and SSB., ((c) 2006 Wiley-Liss, Inc.)

Objectives: An autism susceptibility locus (AUTS1, MIM#608636) has been identified in chromosome 7q31. NrCAM is a candidate gene for AUTS1 because it is expressed in the brain and encodes a receptor involved in nervous system development. Polymorphisms in NrCAM have been reported to be associated with autism susceptibility and with substance abuse, implicating NrCAM in reward circuitry. Self-stimulatory, perseverative behavior in autism might be due to defects in reward circuitry. In addition, models of drug addiction have also borrowed from models of obsessive-compulsive behavior designed to reduce anxiety. Thus, our goals were to replicate previous associations of NrCAM with autism, making use of a large cohort, and to clarify whether NrCAM was associated with a specific endophenotype of autism in the repetitive behaviors and stereotyped interests domains., Methods: We genotyped six NrCAM single nucleotide polymorphisms in 352 families and we tested for association between these polymorphisms and autism in the entire cohort and in two subsets, one with severe obsessive-compulsive behaviors and one with pronounced self-stimulatory behaviors., Results: We found no association between single nucleotide polymorphisms of NrCAM and autism in our large cohort, or in the severe obsessive-compulsive behavior and self-stimulatory behavior subsets. However, we observed a significant overtransmission (21 transmitted vs 6 nontransmitted, chi2=12.054, P=0.0005) of the haplotype G-G-A-G-C-A of rs722519-rs1269622-rs405945-rs6958498-rs401433-rs439587 in the severe obsessive-compulsive behavior subset, likely driven by the G-C haplotype of rs6958498-rs401433, which itself showed significant overtransmission (31 transmitted vs 13 nontransmitted, chi2=8.844, P=0.003)., Conclusions: Overtransmission of particular haplotypes of NrCAM, that may relate to the expression level of NrCAM in the brain, appeared to be associated with autism in the severe obsessive-compulsive behavior subset.

Background: The serotonin transporter (5-HTT) has long been considered likely to play a role in autism. Hyperserotonemia has been consistently found in a proportion of autistic patients, and the use of selective serotonin reuptake inhibitors (SSRIs) can have a positive effect in treating some symptoms of autism. Specific variants of the 5-HTT gene, SLC6A4, especially the insertion-deletion 5-HTTLPR promoter locus, have been found to modulate its expression and transporter function., Methods: We examined the transmission of the short or long allele of 5-HTTLPR locus to affected individuals, using a large cohort of 352 families. In addition, we screened five single nucleotide polymorphisms (SNPs) in the 5' region of SLC6A4 previously reported to be positively associated with autism, as well as 4 additional SNPs also in the 5' region., Results: No association of the 5-HTTLPR locus with autism was found. Furthermore, no evidence for association of any of the nine SNPs covering the SLC6A4 gene, or any of their haplotypes, was observed in our study. Using obsessive-compulsive behaviors (OCB), severe OCBs or rigid-compulsive subsets of our cohort gave the same negative results., Conclusions: SLC6A4 variants do not appear to be significantly involved in the liability to autism.

Autism is characterized by a triad of symptom domains (impaired social interaction, communication deficits, and repetitive behaviors) that vary significantly in their clinical presentation across the population. Within families with more than one affected member, however, discrepant findings exist with regard to symptom variability. Reduced intrafamily variance is of particular importance because it supports an underlying model of genetic heterogeneity in the transmission of autism, and the identification of familial clinical subtypes can be used to select more homogeneous samples for linkage analysis in the future. This study examines whether there are specific features of autism that show decreased variance within 16 families with monozygotic siblings concordant for autism. Evidence for familiality was defined as significantly decreased variance of symptom levels within monozygotic siblingships as compared to between siblingships. Using regression analysis, we demonstrated significant aggregation of symptoms within monozygotic siblingships for two of the three main symptom domains in autism: impairments in communication and social interaction showed significant familiality. Within the repetitive behavior domain, only the categories of circumscribed interests and preoccupation with part-objects showed reduced variance within siblingships. In addition, with the exception of a negative association between the social and behavior domains, partial correlation coefficients did not reveal significant associations between the levels of different symptom domains within families, suggesting that the levels of clinical features seen in autism may be a result of mainly independent genetic traits. Because of presumed genetic heterogeneity and the wide clinical variation seen in autism and other pervasive developmental disorders, selecting probands according to specific features known to show reduced variance within families may provide more homogeneous samples for genetic analysis and strengthen the power to detect the specific genes involved in autism., (Copyright 2004 Wiley-Liss, Inc.)

Objective: Autism/autistic disorder (MIM number 209850) is a complex, largely genetic psychiatric disorder. The authors recently mapped a susceptibility locus for autism to chromosome region 2q24-q33 (MIM number 606053). In the present study, genes across the 2q24-q33 interval were analyzed to identify an autism susceptibility gene in this region., Method: Mutation screening of positional candidate genes was performed in two stages. The first stage involved identifying, in unrelated subjects showing linkage to 2q24-q33, genetic variants in exons and flanking sequence within candidate genes and comparing the frequency of the variants between autistic and unrelated nonautistic subjects. Two single nucleotide polymorphisms (SNPs) that showed evidence for divergent distribution between autistic and nonautistic subjects were identified, both within SLC25A12, a gene encoding the mitochondrial aspartate/glutamate carrier (AGC1). In the second stage, the two SNPs in SLC25A12 were further genotyped in 411 autistic families, and linkage and association tests were carried out in the 197 informative families., Results: Linkage and association were observed between autistic disorder and the two SNPs, rs2056202 and rs2292813, found in SLC25A12. Using either a single affected subject per family or all affected subjects, evidence for excess transmission was found by the Transmission Disequilibrium Test for rs2056202, rs2292813, and a two-locus G*G haplotype. Similar results were observed using TRANSMIT for the analyses. Evidence for linkage was supported by linkage analysis with the two SNPs, with a maximal multipoint nonparametric linkage score of 1.57 and a maximal multipoint heterogeneity lod score of 2.11. Genotype relative risk could be estimated to be between 2.4 and 4.8 for persons homozygous at these loci., Conclusions: A strong association of autism with SNPs within the SLC25A12 gene was demonstrated. Further studies are needed to confirm this association and to decipher any potential etiological role of AGC1 in autism.

Parents of autistic probands with high and low rates of repetitive behaviors were compared for rates of obsessive-compulsive traits and disorder. The rate of repetitive behaviors was assessed using the Autism Diagnostic Interview-Revised (ADI-R) in 176 autistic probands from 57 multiplex families. Obsessive-compulsive disorder (OCD) in parents was determined by direct interview using a parental history questionnaire, with screening for obsessive-compulsive traits using the Yale-Brown Obsessive-Compulsive Scale checklist. Children who had high total scores on the repetitive behavior domain of the ADI-R were significantly more likely to have one or both parents with obsessive-compulsive traits or disorder compared with children who had low total scores on this domain. Children with high scores on D1/D2 of the ADI-R (narrow restricted interests and rituals) were significantly more likely to have one or both parents with OCD, especially fathers, than those with low D1/D2. The occurrence of obsessive-compulsive traits or disorder in parents of autistic children in multiplex families is significantly more likely if autistic children have a high occurrence of repetitive behaviors. Dichotomizing autistic probands by severity and type of repetitive behaviors (circumscribed interests and compulsive rituals) may yield more homogenous groups, which could be helpful in genetic linkage studies.

Heterogeneity in autism impairs efforts to localize and identify the genes underlying this disorder. As autism comprises severe but variable deficits and traits in three symptom domains (social interaction, communication, and repetitive behaviors) and shows variability in the presence and emergence of useful phrase speech, different genetic factors may be associated with each. The affected cases (n=457) in multiply affected siblingships (n=212), including a proband with autism and one or more siblings with either autism or marked deficits in autism symptom domains, were assessed using the Autism Diagnostic Interview, Revised. Symptom domain scores and language features were examined to determine their similarity within siblingships. The variance within siblingships was reduced for the repetitive behavior domain and for delays in and the presence of useful phrase speech. These features and the nonverbal communication subdomain provided evidence of familiality when we considered only the diagnosis of autism to define multiply affected siblingships (cases: n=289; siblingships: n=136). In addition, the same familial features identified also appeared familial for those with autism-related conditions. Finally, the level of severity of almost all of the familial features varied within multiplex siblingships independently. The features identified as familial replicate the combined set suggested in earlier, smaller studies. Furthermore, the familiality of these features extend to related conditions of milder severity than autism and appear to be independent. Making distinctions among families by the severity of these features may be useful for identifying more genetically homogeneous subgroups in studies targeted at genes for specific autism-related symptom domains., (Copyright 2001 Wiley-Liss, Inc.)

Abstract: The PON1 gene, previously found associated with autism spectrum disorders (ASDs), encodes a serum protein responsible for the detoxification of organophosphates (OPs) and able to exert several enzymatic activities. PON1 arylesterase, but not diazoxonase activity, was significantly decreased in 174 ASD patients compared to 175 first-degree relatives and 144 controls (P =2.65×10− 16). First degree relatives displayed intermediate activities, closer to patient than to control levels. Differences between patients, first-degree relatives and controls were especially evident among 164 Italians compared to 329 Caucasian-Americans, because arylesterase activity was significantly higher in Italian controls, compared to Caucasian-American controls (P =2.84×10− 16). Arylesterase activity and PON protein concentrations were not significantly correlated, supporting a functional inhibition of arylesterase activity in ASD patients over quantitative changes in protein amounts. Serum arylesterase activity, in combination with PON1 genotypes at two single nucleotide polymorphisms (SNPs) known to influence protein amounts (rs705379: C-108T) and substrate specificity (rs662: Q192R), was able to discriminate ASD patients from controls with elevated sensitivity and specificity, depending on genotype and ethnic group. Serum arylesterase activity and genotyping at these two SNPs could thus represent an informative biochemical/genetic test, able to aid clinicians in estimating autism risk in ethnic groups with higher baseline arylesterase activity levels. [ABSTRACT FROM AUTHOR]