A common genetic variant in the Neurexin family member CNTNAP2 is related to language but not communication skills in youth with Autism Spectrum Disorder.

One of the candidate genes related to language variability in individuals with Autism Spectrum Disorder (ASD) is the contactin-associated protein-like 2 gene (CNTNAP2), a member of the Neurexin family. However, due to the different assessment tools used, it is unknown whether the polymorphisms of the CNTNAP2 gene are linked to structural language skills or more general communication abilities. A total of 302 youth aged 7 to 18 years participated in the present study: 131 verbal youth with ASD (62 female), 130 typically developing (TD) youth (64 female), and 41 unaffected siblings (US) of youth with ASD (25 female). Blood samples were collected to obtain genomic DNA and processed by the Rutgers University Cell and Data Repository or using standard protocols (Gentra Puregene Blood DNA extraction kit; Qiagen). Language and verbal communication skills were screened with the Clinical Evaluation of Language Fundamental-4 (CELF-4) and Vineland-II Communication domain, subsequently. The results showed that the polymorphism of CNTNAP2 (SNP rs2710102) was related to structural language abilities, such that participants carrying the A-allele had lower language skills in comparison to the G-allele homozygotes. No relationship was found between the polymorphism of CNTNAP2 and more general communication abilities. Although the study revealed genetic mechanisms that are associated with CELF-4 measures but not Vineland-II in youth with ASD, follow-up studies are needed that will include measures of language and communication that are less correlated to each other as well as will include a group of minimally and/or non-verbal individuals with ASD.

Disentangling negative and positive symptoms in schizophrenia and autism spectrum disorder.

Autism spectrum disorder (ASD) and schizophrenia (SZ) share traits, especially in social skills and negative symptoms, and to a lesser degree positive symptoms. Differential diagnosis can be challenging and discerning expressive and experiential negative symptoms may provide knowledge with potential diagnostic and functional relevance that can guide treatment. Two exploratory factor analyses (EFA) were conducted to reveal the underlying dimensions of negative and positive symptoms using the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Positive Symptoms & Negative Symptoms (SAPS/SANS) and the Autism Diagnostic Observation Schedule-Generic (ADOS-G). Three factors emerged from the negative symptom EFA (70.5 % variance): NF1) Expressive Negative; NF2) Experiential Negative; and NF3) Preoccupation, Absorption & Expressive Affective Flattening. Three positive factors emerged (68.6 % variance): PF1) Hallucinations-Delusions; PF2) Grandiosity; and PF3) Thought Disorder-ADOS positive Symptoms. SZ showed higher PF1 scores, and ASD had higher PF3 scores. No differences between groups were observed in the negative factors. Across groups, all negative factors were inversely associated with quality of life. Only NF1 and NF2 and PF1 were detrimentally related to social functioning. A discriminant function analysis using all factors classified correctly 84.4 % of participants, with PF1, NF1 followed by NF2 being the best predictors of diagnosis. Expressive negative followed by Experiential negative symptoms are of diagnostic value independent of and beyond SZ-related positive symptoms and are related with detrimental functioning. Findings confirm the need to distinctively target negative symptoms, and specific SZ-related and ASD-related positive symptoms, and especially the use of several assessment tools for diagnostic classification.

Time is of the essence: Age at autism diagnosis, sex assigned at birth, and psychopathology.

LAY ABSTRACT: Previous research has shown that girls/women are diagnosed later than boys/men with autism. Individuals who are diagnosed later in life, especially girls/women, have greater anxious and depressive symptoms. Previous research has been limited due to narrow inclusionary criteria for enrollment in studies. The present study uses two samples-one clinic-based, large "real-world" sample and another research-based sample with strict criteria for autism diagnosis-to understand the relationships between diagnostic age, sex assigned at birth, and symptoms of anxiety/depression. In both samples, those who were diagnosed later had greater anxious/depressive symptoms, and anxiety was not predicted by sex. In the clinic-based but not research-based sample, those assigned female at birth were diagnosed later than those assigned male at birth. In the clinic-based sample only, individuals assigned female at birth and who were later diagnosed experienced greater symptoms of anxiety/depression compared to those assigned male who benefited from earlier diagnostic timing. Within the research-based sample, those assigned female at birth had greater depressive symptoms than those assigned male. These findings highlight the importance of timely identification of autism, especially for girls/women who are often diagnosed later. Community-based samples are needed to better understand real-world sex-based and diagnostic age-based disparities in mental health.

The relationship between gamma-band neural oscillations and language skills in youth with Autism Spectrum Disorder and their first-degree relatives.

BACKGROUND: Most children with Autism Spectrum Disorder (ASD) have co-occurring language impairments and some of these autism-specific language difficulties are also present in their non-autistic first-degree relatives. One of the possible neural mechanisms associated with variability in language functioning is alterations in cortical gamma-band oscillations, hypothesized to be related to neural excitation and inhibition balance. METHODS: We used a high-density 128-channel electroencephalography (EEG) to register brain response to speech stimuli in a large sex-balanced sample of participants: 125 youth with ASD, 121 typically developing (TD) youth, and 40 unaffected siblings (US) of youth with ASD. Language skills were assessed with Clinical Evaluation of Language Fundamentals. RESULTS: First, during speech processing, we identified significantly elevated gamma power in ASD participants compared to TD controls. Second, across all youth, higher gamma power was associated with lower language skills. Finally, the US group demonstrated an intermediate profile in both language and gamma power, with nonverbal IQ mediating the relationship between gamma power and language skills. LIMITATIONS: We only focused on one of the possible neural contributors to variability in language functioning. Also, the US group consisted of a smaller number of participants in comparison to the ASD or TD groups. Finally, due to the timing issue in EEG system we have provided only non-phase-locked analysis. CONCLUSIONS: Autistic youth showed elevated gamma power, suggesting higher excitation in the brain in response to speech stimuli and elevated gamma power was related to lower language skills. The US group showed an intermediate pattern of gamma activity, suggesting that the broader autism phenotype extends to neural profiles.

Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder.

The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a new approach to calculating axonal conduction velocity termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1w/T2w ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. We finally provide evidence that these microstructural differences are associated with higher scores on the Social Communication Questionnaire (SCQ) a commonly used diagnostic tool to assess ASD. This study is the first to reveal that ASD involves MRI-measurable in vivo differences of myelin and axonal development with implications for neuronal and behavioral function. We also introduce a novel formulation for calculating aggregate conduction velocity, that is highly sensitive to these changes. We conclude that ASD may be characterized by otherwise intact structural connectivity but that functional connectivity may be attenuated by network properties affecting neural transmission speed. This effect may explain the putative reliance on local connectivity in contrast to more distal connectivity observed in ASD.

Gender, assigned sex at birth, and gender diversity: Windows into diagnostic timing disparities in autism.

LAY ABSTRACT: Later autism diagnosis is associated with risk for mental health problems. Understanding factors related to later autism diagnosis may help reduce mental health risks for autistic people. One characteristic associated with later autism diagnosis is female sex. However, studies often do not distinguish sex assigned at birth and gender identity. Gender diversity may be more common in autistic relative to neurotypical people, and autism is more common in gender-diverse populations. We studied age at autism diagnosis by sex assigned at birth, gender identity, and gender diversity (gender-diverse vs cisgender) status, separately. We studied three separate autistic samples, each of which differed in how they were diagnosed and how they were recruited. The samples included 193 persons (8.0-18.0 years) from a research-recruited academic medical center sample; 1,550 people (1.3-25.4 years) from a clinic-based sample; and 244 people (18.2-30.0 years) from a community-enriched sample. We found significant differences in the clinic-based and community-enriched samples. People assigned female sex at birth were diagnosed with autism significantly later than people assigned male at birth. People of female gender were diagnosed significantly later than people of male gender. Gender-diverse people were diagnosed significantly later than cisgender people. Sex assigned at birth, gender identity, and gender diversity may each show unique relationships with age of autism diagnosis. Differences in how autistic people are diagnosed and recruited are important to consider in studies that examine sex assigned at birth or gender identity. More research into autism diagnosis in adulthood is needed.

Conduction Velocity, G-ratio, and Extracellular Water as Microstructural Characteristics of Autism Spectrum Disorder.

The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a novel metric termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1w/T2w ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. We finally provide evidence that these microstructural differences are associated with higher scores on the Social Communication Questionnaire (SCQ) a commonly used diagnostic tool to assess ASD. This study is the first to reveal that ASD involves MRI-measurable in vivo differences of myelin and axonal development with implications for neuronal and behavioral function. We also introduce a novel neuroimaging metric, aggregate conduction velocity, that is highly sensitive to these changes. We conclude that ASD may be characterized by otherwise intact structural connectivity but that functional connectivity may be attenuated by network properties affecting neural transmission speed. This effect may explain the putative reliance on local connectivity in contrast to more distal connectivity observed in ASD.

Pubertal maturation and timing effects on resting state electroencephalography in autistic and comparison youth.

Autistic and comparison individuals differ in resting-state electroencephalography (EEG), such that sex and age explain variability within and between groups. Pubertal maturation and timing may further explain variation, as previous work has suggested alterations in pubertal timing in autistic youth. In a sample from two studies of 181 autistic and 94 comparison youth (8 years to 17 years and 11 months), mixed-effects linear regressions were conducted to assess differences in EEG (midline power for theta, alpha, and beta frequency bands). Alpha power was analyzed as a mediator in the relation between pubertal maturation and timing with autistic traits in the autistic groups to understand the role of puberty in brain-based changes that contribute to functional outcomes. Individuals advanced in puberty exhibited decreased power in all bands. Those who experienced puberty relatively early showed decreased power in theta and beta bands, controlling for age, sex, and diagnosis. Autistic individuals further along in pubertal development exhibited lower social skills. Alpha mediated the relation between puberty and repetitive behaviors. Pubertal maturation and timing appear to play unique roles in the development of cognitive processes for autistic and comparison youth and should be considered in research on developmental variation in resting-state EEG.

Epigenetic modification of the oxytocin receptor gene is associated with child-parent neural synchrony during competition.

Interpersonal neural synchrony (INS) occurs when neural electrical activity temporally aligns between individuals during social interactions. It has been used as a metric for interpersonal closeness, often during naturalistic child-parent interactions. This study evaluated whether other biological correlates of social processing predicted the prevalence of INS during child-parent interactions, and whether their observed cooperativity modulated this association. Child-parent dyads (n = 27) performed a visuospatial tower-building task in cooperative and competitive conditions. Neural activity was recorded using mobile electroencephalogram (EEG) headsets, and experimenters coded video-recordings post-hoc for behavioral attunement. DNA methylation of the oxytocin receptor gene (OXTRm) was measured, an epigenetic modification associated with reduced oxytocin activity and socioemotional functioning. Greater INS during competition was associated with lower child OXTRm, while greater behavioral attunement during competition and cooperation was associated with higher parent OXTRm. These differential relationships suggest that interpersonal dynamics as measured by INS may be similarly reflected by other biological markers of social functioning, irrespective of observed behavior. Children's self-perceived communication skill also showed opposite associations with parent and child OXTRm, suggesting complex relationships between children's and their parents' social functioning. Our findings have implications for ongoing developmental research, supporting the utility of biological metrics in characterizing interpersonal relationships.

Frontal EEG alpha asymmetry in youth with autism: Sex differences and social-emotional correlates.

In youth broadly, EEG frontal alpha asymmetry (FAA) associates with affective style and vulnerability to psychopathology, with relatively stronger right activity predicting risk for internalizing and externalizing behaviors. In autistic youth, FAA has been related to ASD diagnostic features and to internalizing symptoms. Among our large, rigorously characterized, sex-balanced participant group, we attempted to replicate findings suggestive of altered FAA in youth with an ASD diagnosis, examining group differences and impact of sex assigned at birth. Second, we examined relations between FAA and behavioral variables (ASD features, internalizing, and externalizing) within autistic youth, examining effects by sex. Third, we explored whether the relation between FAA, autism features, and mental health was informed by maternal depression history. In our sample, FAA did not differ by diagnosis, age, or sex. However, youth with ASD had lower total frontal alpha power than youth without ASD. For autistic females, FAA and bilateral frontal alpha power correlated with social communication features, but not with internalizing or externalizing symptoms. For autistic males, EEG markers correlated with social communication features, and with externalizing behaviors. Exploratory analyses by sex revealed further associations between youth FAA, behavioral indices, and maternal depression history. In summary, findings suggest that individual differences in FAA may correspond to social-emotional and mental health behaviors, with different patterns of association for females and males with ASD. Longitudinal consideration of individual differences across levels of analysis (e.g., biomarkers, family factors, and environmental influences) will be essential to parsing out models of risk and resilience among autistic youth.

Modeling idiopathic autism in forebrain organoids reveals an imbalance of excitatory cortical neuron subtypes during early neurogenesis.

Idiopathic autism spectrum disorder (ASD) is highly heterogeneous, and it remains unclear how convergent biological processes in affected individuals may give rise to symptoms. Here, using cortical organoids and single-cell transcriptomics, we modeled alterations in the forebrain development between boys with idiopathic ASD and their unaffected fathers in 13 families. Transcriptomic changes suggest that ASD pathogenesis in macrocephalic and normocephalic probands involves an opposite disruption of the balance between excitatory neurons of the dorsal cortical plate and other lineages such as early-generated neurons from the putative preplate. The imbalance stemmed from divergent expression of transcription factors driving cell fate during early cortical development. While we did not find genomic variants in probands that explained the observed transcriptomic alterations, a significant overlap between altered transcripts and reported ASD risk genes affected by rare variants suggests a degree of gene convergence between rare forms of ASD and the developmental transcriptome in idiopathic ASD.

Intrinsic neural timescales in autism spectrum disorder and schizophrenia. A replication and direct comparison study.

Intrinsic neural timescales (INT) reflect the duration for which brain areas store information. A posterior-anterior hierarchy of increasingly longer INT has been revealed in both typically developed individuals (TD), as well as persons diagnosed with autism spectrum disorder (ASD) and schizophrenia (SZ), though INT are, overall, shorter in both patient groups. In the present study, we aimed to replicate previously reported group differences by comparing INT of TD to ASD and SZ. We partially replicated the previously reported result, showing reduced INT in the left lateral occipital gyrus and the right post-central gyrus in SZ compared to TD. We also directly compared the INT of the two patient groups and found that these same two areas show significantly reduced INT in SZ compared to ASD. Previously reported correlations between INT and symptom severity were not replicated in the current project. Our findings serve to circumscribe the brain areas that can potentially play a determinant role in observed sensory peculiarities in ASD and SZ.

Centering the Inner Experience of Autism: Development of the Self-Assessment of Autistic Traits.

Current tools for identifying autism are critiqued for their lack of specificity and sensitivity, especially in autistic people who are older, have higher verbal ability or significant compensatory skills, and are not cisgender boys. This may reflect the following: the historical focus of autism research on White (cisgender) male, upper and middle class children; limited interest in the inner, lived experience of autism; and the predominance of a deficit-based model of autism. We report here on the first attempt of which we are aware to develop a clinical self-report measure of autistic traits as described by autistic people. We believe this is an advance in methodology because prior work in the development of autistic trait/diagnostic measures has prioritized the perspectives of nonautistic clinicians and scientists. The measure was developed under the leadership of two autistic researchers and constructed by leveraging descriptions of autism by autistic people to generate items designed to encompass the range of the autistic experience, using strength-based, accessible language. The team utilized iterative feedback from a panel of autistic experts to refine and enhance the measure, called the Self Assessment of Autistic Traits (SAAT). It is intended for people 16 years or older and uses a format that is designed to increase its accessibility and acceptability for autistic respondents. Future work will report on the preliminary psychometrics of the SAAT, with a long-term goal of advancing our understanding of the inner autistic experience and enhancing the clinical and scientific assessment of autism.

Why is this topic important?: Some people, especially older people, and those who can "mask" their autism, are missed by the current autism assessment tools. This can keep them from getting supports or getting connected to autistic communities. This can harm their well-being and independence. The tools we currently have to assess autism are important, but they were not developed with people who represent the full range of genders, ages, abilities, and cultural identities that characterize autism. Furthermore, current tools emphasize behaviors that other people observe, for example, making eye contact, and do not fully explore the lived or inner experience of autism. What is the purpose of this article?: This article describes the first attempt we know of to begin developing a self-report measure of autistic traits as described by autistic people. What did the authors do?: The authors started by reading what autistic people had to say about autism. They used those readings to come up with initial ideas about autistic experience. Then they used those ideas to write questions for a questionnaire about autistic traits. They asked autistic experts to review the questionnaire and made changes based on what they said. How did the authors work together?: This project was led by two autistic researchers who worked with a team of nonautistic researchers experienced in different research methods. A panel of autistic experts, including both autistic scientist and community leaders, also provided important input. Some of those methods were community-based research, Delphi panels, cognitive interviewing, and measure development. The research team made decisions together. The autistic researchers made the final decisions if there was disagreement. What did they produce?: They produced a preliminary version of the Self Assessment of Autistic Traits (SAAT). The SAAT is a questionnaire that asks if a person has common autistic experiences and traits. It has 58 items that are written with the aim of being respectful and using accessible language. The questionnaire is designed to work with common autistic thinking styles. How will this help autistic adults now or in the future?: The long-term goal is to create a reliable and valid self-report questionnaire that people 16 years old and older can complete to measure their autistic traits. We believe that this could be an important tool for advancing our understanding of the inner autistic experience of autism. This could improve how we assess autistic adults and how we research and think about autism.

The autism spectrum among transgender youth: default mode functional connectivity.

The common intersection of autism and transgender identities has been described in clinical and community contexts. This study investigates autism-related neurophenotypes among transgender youth. Forty-five transgender youth, evenly balanced across non-autistic, slightly subclinically autistic, and full-criteria autistic subgroupings, completed resting-state functional magnetic resonance imaging to examine functional connectivity. Results confirmed hypothesized default mode network (DMN) hub hyperconnectivity with visual and motor networks in autism, partially replicating previous studies comparing cisgender autistic and non-autistic adolescents. The slightly subclinically autistic group differed from both non-autistic and full-criteria autistic groups in DMN hub connectivity to ventral attention and sensorimotor networks, falling between non-autistic and full-criteria autistic groups. Autism traits showed a similar pattern to autism-related group analytics, and also related to hyperconnectivity between DMN hub and dorsal attention network. Internalizing, gender dysphoria, and gender minority-related stigma did not show connectivity differences. Connectivity differences within DMN followed previously reported patterns by designated sex at birth (i.e. female birth designation showing greater within-DMN connectivity). Overall, findings suggest behavioral diagnostics and autism traits in transgender youth correspond to observable differences in DMN hub connectivity. Further, this study reveals novel neurophenotypic characteristics associated with slightly subthreshold autism, highlighting the importance of research attention to this group.

The Gender Self-Report: A multidimensional gender characterization tool for gender-diverse and cisgender youth and adults.

Gender identity is a core component of human experience, critical to account for in broad health, development, psychosocial research, and clinical practice. Yet, the psychometric characterization of gender has been impeded due to challenges in modeling the myriad gender self-descriptors, statistical power limitations related to multigroup analyses, and equity-related concerns regarding the accessibility of complex gender terminology. Therefore, this initiative employed an iterative multi-community-driven process to develop the Gender Self-Report (GSR), a multidimensional gender characterization tool, accessible to youth and adults, nonautistic and autistic people, and gender-diverse and cisgender individuals. In Study 1, the GSR was administered to 1,654 individuals, sampled through seven diversified recruitments to be representative across age (10-77 years), gender and sexuality diversity (∼33% each gender diverse, cisgender sexual minority, cisgender heterosexual), and autism status (> 33% autistic). A random half-split subsample was subjected to exploratory factor analytics, followed by confirmatory analytics in the full sample. Two stable factors emerged: Nonbinary Gender Diversity and Female-Male Continuum (FMC). FMC was transformed to Binary Gender Diversity based on designated sex at birth to reduce collinearity with designated sex at birth. Differential item functioning by age and autism status was employed to reduce item-response bias. Factors were internally reliable. Study 2 demonstrated the construct, convergent, and ecological validity of GSR factors. Of the 30 hypothesized validation comparisons, 26 were confirmed. The GSR provides a community-developed gender advocacy tool with 30 self-report items that avoid complex gender-related "insider" language and characterize diverse populations across continuous multidimensional binary and nonbinary gender traits. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Linear discriminant analysis of phenotypic data for classifying autism spectrum disorder by diagnosis and sex.

Autism Spectrum Disorder (ASD) is a developmental condition characterized by social and communication differences. Recent research suggests ASD affects 1-in-44 children in the United States. ASD is diagnosed more commonly in males, though it is unclear whether this diagnostic disparity is a result of a biological predisposition or limitations in diagnostic tools, or both. One hypothesis centers on the 'female protective effect,' which is the theory that females are biologically more resistant to the autism phenotype than males. In this examination, phenotypic data were acquired and combined from four leading research institutions and subjected to multivariate linear discriminant analysis. A linear discriminant model was trained on the training set and then deployed on the test set to predict group membership. Multivariate analyses of variance were performed to confirm the significance of the overall analysis, and individual analyses of variance were performed to confirm the significance of each of the resulting linear discriminant axes. Two discriminant dimensions were identified between the groups: a dimension separating groups by the diagnosis of ASD (LD1: 87% of variance explained); and a dimension reflective of a diagnosis-by-sex interaction (LD2: 11% of variance explained). The strongest discriminant coefficients for the first discriminant axis divided the sample in domains with known differences between ASD and comparison groups, such as social difficulties and restricted repetitive behavior. The discriminant coefficients for the second discriminant axis reveal a more nuanced disparity between boys with ASD and girls with ASD, including executive functioning and high-order behavioral domains as the dominant discriminators. These results indicate that phenotypic differences between males and females with and without ASD are identifiable using parent report measures, which could be utilized to provide additional specificity to the diagnosis of ASD in female patients, potentially leading to more targeted clinical strategies and therapeutic interventions. The study helps to isolate a phenotypic basis for future empirical work on the female protective effect using neuroimaging, EEG, and genomic methodologies.

Increased perceived stress is negatively associated with activities of daily living and subjective quality of life in younger, middle, and older autistic adults.

Few studies have examined self-reported perceived stress in autistic adults. Existing studies have included relatively small, predominantly male samples and have not included older autistic adults. Using a large autistic sample (N = 713), enriched for individuals designated female at birth (59.3%), and spanning younger, middle, and older adulthood, we examined perceived stress and its associations with independence in activities of daily living and subjective quality of life (QoL). Perceived stress for autistic adults designated male or female at birth was compared to their same birth-sex counterparts in a general population sample. In addition, within the autistic sample, effects of sex designated at birth, age, and their interaction were examined. Regression modeling examined associations between perceived stress and independence in activities of daily living and domains of subjective QoL in autistic adults, after controlling for age, sex designated at birth, and household income. Autistic adults reported significantly greater perceived stress than a general population comparison sample. Relative to autistic adults designated male at birth, those designated female at birth demonstrated significantly elevated perceived stress. Perceived stress contributed significantly to all regression models, with greater perceived stress associated with less independence in activities of daily living, and poorer subjective QoL across all domains-Physical, Psychological, Social, Environment, and Autism-related QoL. Findings are contextualized within the literature documenting that autistic individuals experience elevated underemployment and unemployment, heightened rates of adverse life events, and increased exposure to minority stress. LAY SUMMARY: This study looked at self-reported perceived stress in a large sample of autistic adults. Autistic adults reported more perceived stress than non-autistic adults. Autistic individuals designated female at birth reported higher stress than autistic individuals designated male at birth. In autistic adults, greater perceived stress is related to less independence in activities of daily living and poorer subjective quality of life.

Amygdala-prefrontal connectivity in children with maladaptive aggression is modulated by social impairment.

Aggressive behavior is common across childhood-onset psychiatric disorders and is associated with impairments in social cognition and communication. The present study examined whether amygdala connectivity and reactivity during face emotion processing in children with maladaptive aggression are moderated by social impairment. This cross-sectional study included a well-characterized transdiagnostic sample of 101 children of age 8-16 years old with clinically significant levels of aggressive behavior and 32 typically developing children without aggressive behavior. Children completed a face emotion perception task of fearful and calm faces during functional magnetic resonance imaging. Aggressive behavior and social functioning were measured by standardized parent ratings. Relative to controls, children with aggressive behavior showed reduced connectivity between the amygdala and the dorsolateral prefrontal cortex (PFC) during implicit emotion processing. In children with aggressive behavior, the association between reduced amygdala-ventrolateral PFC connectivity and greater severity of aggression was moderated by greater social impairment. Amygdala reactivity to fearful faces was also associated with severity of aggressive behavior for children without social deficits but not for children with social deficits. Social impairments entail difficulties in interpreting social cues and enacting socially appropriate responses to frustration or provocation, which increase the propensity for an aggressive response via diminished connectivity between the amygdala and the ventral PFC.

Right Anterior Theta Hypersynchrony as a Quantitative Measure Associated with Autistic Traits and K-Cl Cotransporter KCC2 Polymorphism.

Our aim was to use theta coherence as a quantitative trait to investigate the relation of the polymorphisms in NKCC1 (rs3087889) and KCC2 (rs9074) channel protein genes to autistic traits (AQ) in neurotypicals. Coherence values for candidate connection regions were calculated from eyes-closed resting EEGs in two independent groups. Hypersynchrony within the right anterior region was related to AQ in both groups (p < 0.05), and variability in this hypersynchrony was related to the rs9074 polymorphism in the total group (p < 0.05). In conclusion, theta hypersynchrony within the right anterior region during eyes-closed rest can be considered a quantitative measure for autistic traits. Replicating our findings in two independent populations with different backgrounds strengthens the validity of the current study.