Social Responsiveness Scale Research Articles

Abnormal spontaneous brain activity in females with autism spectrum disorders.

To date, most studies on autism spectrum disorder (ASD) have focused on sample sets that were primarily or entirely composed of males; brain spontaneous activity changes in females remain unclear. The purpose of this study was to explore changes in the brain spontaneous neural activity in females with ASD. In this study, resting-state functional magnetic resonance images (rs-fMRI) of 41 females with ASD and 41 typically developing (TD) controls were obtained from the ABDIE database. The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) of the two groups were calculated to detect the regional brain activity. A two independent sample t-test was used to analyze differences between the ASD and TD groups and a p-value <0.05 was considered statistically significant after false discovery rate (FDR) correction. Pearson correlation analysis was conducted between social responsiveness scale (SRS) scores and the local activity of significantly different brain regions. Compared with the typically developing (TD) group, the values of ALFF and ReHo were significantly increased in the left superior temporal gyrus (STG), while the values of ReHo were significantly decreased in the left superior frontal gyrus (SFG), left middle occipital gyrus (MOG), bilateral superior parietal lobule (SPL), and bilateral precuneus in the females with ASD group. Correlation analysis showed that the ReHo of the right precuneus was positively correlated to the total SRS, social communication, and autistic mannerisms. Spontaneous activity changes in females with ASD involved multiple brain regions and were related to clinical characteristics. Our results may provide some help for further exploring the neurobiological mechanism of females with ASD.

Sex differences in placenta-derived markers and later autistic traits in children

Autism is more prevalent in males and males on average score higher on measures of autistic traits. Placental function is affected significantly by the sex of the fetus. It is unclear if sex differences in placental function are associated with sex differences in the occurrence of autistic traits postnatally. To assess this, concentrations of angiogenesis-related markers, placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) were assessed in maternal plasma of expectant women in the late 1st (mean= 13.5 [SD = 2.0] weeks gestation) and 2nd trimesters (mean=20.6 [SD = 1.2] weeks gestation), as part of the Generation R Study, Rotterdam, the Netherlands. Subsequent assessment of autistic traits in the offspring at age 6 was performed with the 18-item version of the Social Responsiveness Scale (SRS). Associations of placental protein concentrations with autistic traits were tested in sex-stratified and cohort-wide regression models. Cases with pregnancy complications or a later autism diagnosis (n = 64) were also assessed for differences in placenta-derived markers. sFlt-1 levels were significantly lower in males in both trimesters but showed no association with autistic traits. PlGF was significantly lower in male pregnancies in the 1st trimester, and significantly higher in the 2nd trimester, compared to female pregnancies. Higher PlGF levels in the 2nd trimester and the rate of PlGF increase were both associated with the occurrence of higher autistic traits (PlGF-2nd: n = 3469,b = 0.24 [SE = 0.11], p = 0.03) in both unadjusted and adjusted linear regression models that controlled for age, sex, placental weight and maternal characteristics. Mediation analyses showed that higher autistic traits in males compared to females were partly explained by higher PlGF or a faster rate of PlGF increase in the second trimester (PlGF-2nd: n = 3469, ACME: b = 0.005, [SE = 0.002], p = 0.004). In conclusion, higher PlGF levels in the 2nd trimester and a higher rate of PlGF increase are associated with both being male, and with a higher number of autistic traits in the general population.

Cariprazine in Pediatric Patients with Autism Spectrum Disorder: Results of a Pharmacokinetic, Safety and Tolerability Study.

Objective: Cariprazine is a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist approved to treat adults with schizophrenia and manic/mixed or depressive episodes associated with bipolar I disorder. This study, which is the first to evaluate cariprazine in pediatric patients with autism spectrum disorder (ASD) (including children 5-9 years of age) using an oral solution formulation, evaluated the safety, tolerability, pharmacokinetics (PK), and exploratory efficacy of cariprazine and its two major active metabolites, desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR). Methods: This clinical pharmacology, open-label, multiple-dose study enrolled 25 pediatric patients from 5 to 17 years of age, who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for ASD. All patients began treatment with cariprazine 0.5 mg once daily (QD) and underwent a titration over 7 days to maintenance doses of 1.5 or 3 mg QD for patients 13-17 years of age at Screening, 0.75 or 1.5 mg QD for patients 10-12 years of age at Screening, and 0.5 or 1.5 mg QD for patients 5-9 years of age at Screening. After 6 weeks total of dosing, there was a 6-week follow-up period. Study assessments included adverse events (AEs), safety parameters, noncompartmental PK parameters, and exploratory efficacy assessments, including the Aberrant Behavior Checklist-Irritability Subscale (ABC-I), Clinical Global Impressions (CGI-S), Caregiver Global Impressions (CgGI-S), Children's Yale-Brown Obsessive Compulsiveness Scale Modified for ASD (CYBOCS-ASD), Social Responsiveness Scale (SRS), and Vineland Adaptive Behavior Scale (VABS-III). Results: All AEs were mild or moderate in severity. Most frequent treatment-emergent adverse events (TEAEs) were increased weight, increased alanine aminotransferase, increased appetite, dizziness, agitation, and nasal congestion. Increases in weight were not considered clinically meaningful. Two subjects reported extrapyramidal symptom-related TEAEs that resolved without leading to discontinuation. Dose-normalized exposures of all analytes were modestly higher in pediatric patients from 5 to 9 years of age when compared to older patients. Consistent with previous studies, at steady state, the rank of exposure in plasma was DDCAR > cariprazine > DCAR. There was numerical improvement on all exploratory endpoints (ABC-I, CGI-S, CgGI-S, CYBOCS-ASD, SRS, and VABS-III). Conclusions: PK of cariprazine and its metabolites were characterized in pediatric patients with ASD at doses up to 3 mg QD (13-17 years) and 1.5 mg QD (5-12 years). Caripazine treatment was generally well tolerated and results from this study will inform the selection of appropriate pediatric doses for subsequent studies.

Metaverse-based social skills training programme for children with autism spectrum disorder to improve social interaction ability: an open-label, single-centre, randomised controlled pilot trial.

Autism spectrum disorder (ASD) is characterised by abnormalities in social interactions and restricted and repetitive behaviors. Children with high-functioning ASD (HFASD), lack social communication skills, do not interact with others, and lack peer relationships. We aimed to develop, and evaluate the feasibility of, a metaverse-based programme to enhance the social skills of children with HFASD. This open-label, single-centre, pilot parallel randomised controlled trial (RCT) was conducted on boys aged 7-12 years with HFASD. Children were recruited from a treatment centre for children with HFASD in Korea or by self-referral through online community webpages for the parents of children with HFASD. Participants were randomly assigned (1:1) by a blinded researcher to receive either four weeks of a metaverse-based social skills training programme or a control group. Randomisation was stratified by age (children aged 7-9 and 10-12 years) using permuted blocks (block size 4). The metaverse-based social skills training programme was delivered via the metaverse platforms (Roblox) and Zoom. Children in the intervention group completed the metaverse-based social skills training programme at home for four weeks. The intervention consisted of four sessions, one session per week, for 60min each. The control group did not receive any interventions. The primary outcome measure was the median change in the Social Responsiveness Scale-2 (SRS-2) scores from pre-to post-intervention. SRS-2 is an assessment tool used to confirm the effectiveness of social interactions. Higher scores indicate lower social functioning. The trial is registered with CRIS Registration Number; KCT0006859. Between February 14, 2022, and March 31, 2022, 20 participants were enrolled. Overall, 15 children (median [Interquartile range (IQR)] age, intervention group: 9.0 [8.0-10.0]; control group: 8.5 [8.0-10.0]) participated in the programme. The intervention group included nine participants (60%), and the control group included six participants (40%). The SRS-2 total scores for the intervention group decreased from baseline 96.0 (IQR: 74.0-112.0) to post-intervention 85.0 (IQR: 84.0-103.0). The group median difference in SRS-2 scores between the intervention and control groups was 11.5 (95% CI: 8.5-14.0), with a further reduction in the intervention group. Similar trends were seen for social cognition (group median difference, 95% CI: 2.0, 1.0-4.0), social communication (group median difference, 95% CI: 2.0, 1.0-4.0), and autistic mannerism (group median difference, 95% CI: 4.0, 1.0-5.0). There were no adverse events related to study participation. The findings of this feasibility study suggest that children with HFASD can potentially be familiarised, through metaverse-based programmes, with real-life social situations to improve sociality and reduce emotional and behavioural problems. Such interventions could be delivered at home and possibly be extended to target groups that have difficulty in interacting with peers offline. The Institute of Information & Communications Technology Planning & Evaluation grant, via the Ministry of Science and ICT of the South Korean Government.

The Association Between Prenatal Infection and Adolescent Behavior: Investigating Multiple Prenatal, Perinatal, and Childhood Second Hits

Exposure to infections during pregnancy may be a potential risk factor for later psychopathology, but large-scale epidemiological studies investigating associations between prenatal infection and long-term offspring behavioral problems in the general population are scarce. In our study, we aimed to investigate the following: (1) the association between prenatal infection and adolescent behavior, (2) putative underlying pathways (mediation), and (3) "second hits" interacting with prenatal infection to increase the risk of adolescent behavior problems (moderation). Our study was embedded in a prospective Dutch pregnancy cohort (Generation R; n= 2,213 mother-child dyads). We constructed a comprehensive prenatal infection score comprising common infections for each trimester of pregnancy. At age 13 to 16 years, we assessed total, internalizing, and externalizing problems, and autistic traits using the Child Behavioral Checklist and the Social Responsiveness Scale, respectively. We investigated maternal lifestyle and nutrition, perinatal factors (placental health and delivery outcomes), and child health (lifestyle, traumatic events, infections) as mediators and moderators. We observed associations of prenatal infection with adolescent total behavioral, internalizing, and externalizing problems. The association between prenatal infection and internalizing problems was moderated by higher levels of maternal psychopathology, alcohol and tobacco use, and a higher number of traumatic childhood events. We found no association between prenatal infection and autistic traits. Yet, children exposed to prenatal infections and maternal substance use, and/or traumatic childhood events, had a higher risk of autistic traits in adolescence. Prenatal infection may be a risk factor for later psychiatric problems as well as a disease primer making individuals susceptible to other hits later in life. Prenatal maternal infection and adverse neurodevelopment: a structural equation modelling approach to downstream environmental hits; https://osf.io/cp85a; cp85a. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex and gender balance in the recruitment of human participants.

The Effect of Attention on Auditory Processing in Adults on the Autism Spectrum.

This study examined the effect of attention on auditory processing in autistic individuals. Electroencephalography data were recorded during two attention conditions (passive and active) from 24 autistic adults and 24 neurotypical controls, ages 17-30 years. The passive condition involved only listening to the clicks and the active condition involved a button press following single clicks in a modified paired-click paradigm. Participants completed the Adolescent/Adult Sensory Profile and the Social Responsiveness Scale 2. The autistic group showed delayed N1 latencies and reduced evoked and phase-locked gamma power compared to neurotypical peers across both clicks and conditions. Longer N1 latencies and reduced gamma synchronization predicted greater social and sensory symptoms. Directing attention to auditory stimuli may be associated with more typical neural auditory processing in autism.

Association between maternal labour epidural analgesia and autistic traits in offspring

Study objectiveStudies investigating associations between maternal epidural analgesia (MEA) and autism spectrum disorder (ASD) in the offspring are conflicting and lack prospective neurobehavioral follow-up assessments for autistic traits. We aim to prospectively investigate associations between MEA and autistic traits in the offspring. DesignProspective neurobehavioral observational cohort study. SettingSingaporean tertiary healthcare institutions. PatientsParticipants recruited were singleton non-IVF children, >36 weeks gestation, delivered via normal vaginal delivery by mothers >18 years of age, delivered in Singapore from June 2009–September 2010 and followed up over 7 years. InterventionsExposure to maternal epidural analgesia during delivery. MeasurementsThe primary outcome is an abnormal Social Responsiveness Scale (SRS) T score at 7 years (≥60 points). Secondary outcomes include the diagnosis of ASD and abnormal scores for autistic traits assessed via a neurobehavioral battery comprising: CBCL (child behavioural checklist), Q-CHAT (Quantitative Checklist for Autism in Toddlers), and Bayley-III. Multivariable analyses adjusting for maternal and offspring characteristics were performed. Main results704 out of 769 mother-child dyads recruited fulfilled the criteria for analysis. 365/704 mothers received MEA.The incidence of an abnormal SRS score at 7 years in offspring exposed to MEA was 19.9%, and 26.1% in non-exposed offspring (p = 0.154). Multivariable analysis did not demonstrate a significant association between MEA and abnormal SRS scores at 7 years (O.R.0.726, 95% C·I. 0.394–1.34, p = 0.305). After adjustment for maternal and fetal demographics, exposure to MEA was not significantly associated with an abnormal screen in all other tests for autistic traits.The clinical incidence of ASD was 1.76% in children without exposure to MEA, and 2.32% in children with MEA exposure (p = 0.506). ConclusionsMEA is not significantly associated with the development of ASD and autistic traits in offspring, assessed over 7 years. Results should be taken into perspective given our wide confidence intervals and small cohort size.

The possible role of sodium leakage channel localization factor-1 in the pathophysiology and severity of autism spectrum disorders

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social, stereotypical, and repetitive behaviors. Neural dysregulation was proposed as an etiological factor in ASD. The sodium leakage channel (NCA), regulated by NLF-1 (NCA localization factor-1), has a major role in maintaining the physiological excitatory function of neurons. We aimed to examine the level of NLF-1 in ASD children and correlate it with the severity of the disease. We examined the plasma levels of NLF-1 in 80 ASD and neurotypical children using ELISA. The diagnosis and severity of ASD were based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), Childhood Autism Rating Score, Social Responsiveness Scale, and Short Sensory Profile. Then, we compared the levels of NLF-1 with the severity of the disease and behavioral and sensory symptoms. Our results showed a significant decrease in the plasma levels of NLF-1 in ASD children compared to neurotypical children (p < 0.001). Additionally, NLF-1 was significantly correlated with the severity of the behavioral symptoms of ASD (p < 0.05). The low levels of NLF-1 in ASD children potentially affect the severity of their behavioral symptoms by reducing neuron excitability through NCA. These novel findings open a new venue for pharmacological and possible genetic research involving NCA in ASD children.

Clinical characteristics of comorbid tic disorders in autism spectrum disorder: exploratory analysis

BackgroundThe frequency, clinical characteristics, and associated symptoms of comorbid tic disorders in individuals with autism spectrum disorder (ASD) remain unclear.MethodsWe included subsets of individuals from a larger genetic study who were diagnosed with ASD (n = 679; age: 4–18 years) and completed the Yale Global Tic Severity Scale (YGTSS) questionnaire. Based on the YGTSS score, the individuals were divided into two groups: ASD only (n = 554) and ASD with tics (n = 125). Individuals were assessed using the verbal and non-verbal intelligence quotient (IQ), Vineland Adaptive Behavior Scale (VABS-2), Social Responsiveness Scale-2 (SRS-2), Child Behavior Checklists (CBCL), and Yale-Brown Obsessive–Compulsive Scale (YBOCS), followed by between-group comparisons. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 26.ResultsTic symptoms were observed in 125 (18.4%) participants; among them, most participants presented both motor and vocal tics (n = 40, 40.0%). The ASD with tics group had a significantly higher average age and full-scale IQ score than the ASD only group. After adjusting for age, the ASD with tics group had significantly higher scores in the SRS-2, CBCL, and YBOCS subdomains than the ASD only group. Furthermore, all variables except the non-verbal IQ and VABS-2 scores were positively correlated with the YGTSS total score. Finally, the proportion of tic symptoms was significantly higher among individuals with a higher IQ score (≥ 70).ConclusionsThe IQ score was positively correlated with the proportion of tic symptoms among individuals with ASD. Moreover, the severity of the core and comorbid symptoms of ASD was associated with the occurrence and severity of tic disorders. Our findings suggest the need for appropriate clinical interventions for individuals with ASD.Trial registration This study retrospectively registered participants

Effectiveness of an Educational Filmmaking Project in Promoting the Psychological Well-Being of Adolescents with Emotive/Behavioural Problems.

Evidence suggests that adolescents respond positively to simple, early interventions, including psychosocial support and educational interventions, even when offered in non-clinical settings. Cinematherapy can help manage life challenges, develop new skills, increase awareness, and offer new ways of thinking about specific problems. This pilot trial was conducted in Italy, aiming to investigate the effects of a six-week filmmaking course on the psychological well-being of adolescents (N = 52) with emotional/behavioural problems and neurodevelopmental disorders. At the end of the project, most participants showed improvements mostly in social skills, such as social cognition (p = 0.049), communication (p = 0.009), and motivation (p = 0.03), detected using the SRS Social Responsiveness Scale. In addition, social awareness (p = 0.001) increased in all patients. Statistically significant differences resulted in four sub-scales of Youth Self-Report Scale: withdrawn/depressed (p = 0.007), social problems (p = 0.003), thought problems (p < 0.001), and rule-breaking behaviour (p = 0.03); these results showed a decrease in emotional and behavioural problems. This study is an innovative therapeutic and educational approach based on the filmmaking art. This research can offer an empirical basis for the effectiveness of alternative therapeutic tools in child and adolescent psychiatric disorders. At the same time, it can be replicated in broader contexts (e.g., school and communities) to promote children's psychological well-being.

The Relationship Between Attention, Sensory Processing, and Social Responsiveness Among Adults on the Autism Spectrum.

This study evaluated attention, sensory processing, and social responsiveness and the relationship between these constructs among autistic and neurotypical adults. Participants included 24 autistic adults (17-30years) and 24 neurotypical peers who completed the Test of Everyday Attention, Adolescent/Adult Sensory Profile (AASP), and the Social Responsiveness Scale-2. Autistic individuals showed greater attention, sensory processing, and social responsiveness challenges compared to neurotypical peers. Using mediation models, we showed that the relationship between attention and social responsiveness was mediated by sensory processing, specifically the low registration and sensation-seeking AASP quadrants. The relationship between attention, sensory processing, and social responsiveness suggests that adults with greater attention issues may have greater sensory and social challenges. Specifically, having poor attention may lead to poor sensory processing skills which compound poor social responsiveness. Understanding the relationships between these domains is critical for developing effective interventions and support for autistic adults.

Air pollution exposure and social responsiveness in childhood: The cincinnati combined childhood cohorts.

Autism Spectrum Disorder (ASD) affects about 1 in 44 children and environmental exposures may contribute to disease onset. Air pollution has been associated with adverse neurobehavioral outcomes, yet little research has examined its association with autistic-like behaviors. Therefore, our objective was to examine the association between exposure to air pollution, including NO2 and PM2.5, during pregnancy and the first year of life to ASD-like behaviors during childhood. Participants (n=435) enrolled in the Cincinnati Childhood Allergy and Air Pollution Study and the Health Outcomes and Measures of the Environment Study were included in the analysis. Daily exposures to NO2 and PM2.5 at the residential addresses of participants were estimated using validated spatiotemporal models and averaged to obtain prenatal and first year exposure estimates. ASD-like behaviors were assessed via the Social Responsiveness Scale (SRS) questionnaire at age 12. Linear regression models adjusting for confounders were applied to estimate the association between pollutants and SRS scores. After adjusting for covariates, the association between NO2 and PM2.5 and SRS scores remained positive but were no longer statistically significant. Prenatal and first year exposure to NO2 were associated with total SRS T-scores with an estimated 0.4 point increase (95% CI: -0.7, 1.6) per 5.2ppb increase in NO2 exposure and 0.7 point (95% CI: -0.3, 1.6) per 4.2ppb increase in NO2 exposure, respectively. For PM2.5, a 2.6μg/m3 increase in prenatal exposure was associated with a 0.1 point increase (95% CI: -1.1, 1.4) in SRS Total T-scores and a 1.3μg/m3 increase first year of life was associated with a 1 point increase (95% CI: -0.2, 2.3). In summary, exposure to NO2 and PM2.5 during pregnancy and the first year of life were not significantly associated with higher autistic-like behaviors measured with SRS scores after adjustment of covariates. Additional research is warranted given prior studies suggesting air pollution contributes to ASD.

A study of the genetic architecture of social responsiveness in families with parental schizophrenia or bipolar disorder and population-based controls

Twin-studies of social responsiveness have reported moderate to high heritabilities, but studies using parent–child data are lacking. Additionally, social impairments have been suggested as a vulnerability marker for schizophrenia and bipolar disorder, but the heritability of social responsiveness in this context is unknown. This study is part of the Danish High Risk and Resilience Study – VIA, comprising families with one parent with schizophrenia (n = 202) or bipolar disorder (n = 120) and population-based controls (PBC, n = 200). Social responsiveness was assessed with The Social Responsiveness Scale, Second Edition (SRS-2). Heritability was estimated from variance components, and a polygenic risk score (PRS) for autism spectrum disorder (ASD) was calculated to assess the genetic relationship between ASD and SRS-2. SRS-2 heritability was moderate to high and significantly different from zero in all groups when the children were rated by the primary caregiver. With teacher ratings, the heritability was lower and only significant in the full cohort and PBC. We found no significant association between SRS-2 and PRS for ASD. Our study confirms that social responsiveness is heritable, but that heritability estimates are affected by the child-respondent relation and familial risk of mental illness. This has implications for clinical practice and research using SRS-2 and provides insight on the familial transmission of mental illness.

Effects of Vitamin D Supplementation on Children with Autism Spectrum Disorder: A Systematic Review and Meta-analysis.

The effect of vitamin D supplementation on individuals with autism spectrum disorder (ASD) is inconclusive. We aimed to conduct a meta-analysis of the available randomized controlled trials (RCTs) to explore whether vitamin D supplementation can improve core symptoms and coexisting conditions in children with ASD. Data were obtained by searching the PubMed, Embase, Web of Science, CINAHL and Cochrane Library databases up to February 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using a random-effects model, mean differences with 95% confidence intervals (CIs) were calculated through a meta-analysis. There were eight RCTs with 266 children with ASD in the present review, among which six RCTs were included in the meta-analysis. Children who received vitamin D supplementation showed a significant improvement in stereotypical behavior scores (pooled mean difference (MD): -1.39; 95% CI: -2.7, -0.07; P = 0.04) with low heterogeneity (I2 = 34%), and there was a trend toward decreased total scores on the Social Responsiveness Scale (SRS) and Childhood Autism Rating Scale (CARS, P = 0.05); however, there were no other significant differences in the core symptoms of ASD and coexisting conditions between groups as measured by the Aberrant Behavior Checklist (ABC). Vitamin D supplementation appears to improve stereotypical behaviors but does not improve other core symptoms and coexisting conditions. Further randomized controlled trials with large sample sizes and individualized doses are needed.

Discrepancy between Clinician-rated and Self-reported Depression Severity is Associated with Adverse Childhood Experience, Autistic-like Traits, and Coping Styles in Mood Disorders

This study aimed to determine if the discrepancy between depression severity rated by clinicians and that reported by patients depends on key behavioral/psychological features in patients with mood disorders. Participants included 100 patients with mood disorders. First, we examined correlations and regressions between scores on the Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI). Second, we divided the participants into those who provided 1) greater ratings for the BDI compared with the HAMD (BDI relative- overrating, BO) group, 2) comparable ratings for the BDI and HAMD (BDI relatively concordant, BC) group, or 3) less ratings for the BDI (BDI relative-underrating, BU) group. Adverse childhood experiences, autistic-like traits, and coping styles were evaluated with a six-item short version of the Childhood Trauma Questionnaire (CTQ-6), the Social Responsiveness Scale for Adults (SRS-A), and the Ways of Coping Checklist (WCCL), respectively. A significant correlation was found between HAMD and BDI scores. Total and emotional abuse subscale scores from the CTQ-6, and the self-blame subscale scores from the WCCL were significantly higher for the BO group compared with the BU group. The BO group also elicited significantly higher SRS-A total scores than did the other groups. These findings suggest that patients with adverse emotional experiences, autistic-like traits, and self-blame coping styles perceive greater distress than that evaluated objectively by clinicians. The results indicate the need for inclusion of subjective assessments to effectively evaluate depressive symptoms in patients deemed to have these psycho- behavioral concerns.

Neuropsychological profile of children with Autism Spectrum Disorder and children with Developmental Language Disorder and its relationship with social communication

Objective The objective of this study was to probe neuropsychological mechanisms of social communication in children with Autism Spectrum Disorders (ASD) and children with Developmental Language Disorders (DLD). Due to overlap of symptoms that include social dysfunction, diagnostic boundaries between these two developmental disorders remain unclear. This study hypothesizes that these two groups of children differ in the characteristics and in the underlying mechanisms of their social issues. Method This study examines a wide range of neuropsychological domains in search of a relationship with social communication. A total of 75 children with ASD and 26 children with DLD are included. A cross-battery assessment of neuropsychological functions is conducted, and social communication is evaluated using the Social Responsiveness Scale (SRS). Results The neuropsychological profile for the ASD group differs from the DLD group, with the former demonstrating higher scores on Visual Processing and Comprehension, whereas the DLD group scores higher on Fluid Reasoning, Visual Processing and Processing Speed. Correlation analysis reveals that the association between neuropsychological domains and social communication differs between the groups. Discussion Children with ASD and DLD clearly have distinctive neuropsychological profiles—their strengths and weaknesses are not equivalent. Such results motivate broad assessment of neuropsychological functions, as this assists in differentiating ASD from DLD for theragnostic purposes.

What are quantitative traits and how can they be used in autism research?

Quantitative traits are measurable characteristics distributed along a continuous scale thought to relate to underlying biology. There is growing interest in the use of quantitative traits in behavioral and psychiatric research, particularly in research on conditions diagnosed based on reports of behaviors, including autism. This brief commentary describes quantitative traits, including defining what they are, how we can measure them, and key considerations for their use in autism research. Examples of measures include behavioral report scales like the Social Responsiveness Scale and Broader Autism Phenotype Questionnaire, as well as biological measurements, like certain neuroimaging metrics; such measures can capture quantitative traits or constructs like the broader autism phenotype, social communication, and social cognition. Quantitative trait measures align with the Research Domain Criteria (RDoC) approach and can be used in autism research to help gain a better understanding of causal pathways and biological processes. They can also be used to aid identification ofgenetic and environmental factors involved in such pathways, and thereby lead to an understanding of influences on traits across the entire population. Finally, in some cases, they may be used to gauge treatment response, and assist screening and clinical characterization of phenotype. In addition, practical benefits of quantitative trait measures include improved statistical power relative to categorical classifications and (for some measures) efficiency. Ultimately, research across autism fields may benefit from incorporating quantitative trait measures as a complement to categorical diagnosis to advance understanding of autism and neurodevelopment.

Understanding the relationship between cerebellar structure and social abilities

BackgroundThe cerebellum contains more than 50% of all neurons in the brain and is involved in a broad range of cognitive functions, including social communication and social cognition. Inconsistent atypicalities in the cerebellum have been reported in individuals with autism compared to controls suggesting the limits of categorical case control comparisons. Alternatively, investigating how clinical dimensions are related to neuroanatomical features, in line with the Research Domain Criteria approach, might be more relevant. We hypothesized that the volume of the “cognitive” lobules of the cerebellum would be associated with social difficulties.MethodsWe analyzed structural MRI data from a large pediatric and transdiagnostic sample (Healthy Brain Network). We performed cerebellar parcellation with a well-validated automated segmentation pipeline (CERES). We studied how social communication abilities—assessed with the social component of the Social Responsiveness Scale (SRS)—were associated with the cerebellar structure, using linear mixed models and canonical correlation analysis.ResultsIn 850 children and teenagers (mean age 10.8 ± 3 years; range 5–18 years), we found a significant association between the cerebellum, IQ and social communication performance in our canonical correlation model.LimitationsCerebellar parcellation relies on anatomical boundaries, which does not overlap with functional anatomy. The SRS was originally designed to identify social impairments associated with autism spectrum disorders.ConclusionOur results unravel a complex relationship between cerebellar structure, social performance and IQ and provide support for the involvement of the cerebellum in social and cognitive processes.

Influence of Auditory Integrative Training on Casein Kinase 2 and Its Impact on Behavioral and Social Interaction in Children with Autism Spectrum Disorder

Considerable disturbances in post-translational protein phosphorylation have recently been discovered in multiple neurological disorders. Casein kinase-2 (CK2) is a tetrameric Ser/Thr protein kinase that phosphorylates a large number of substrates and contributes in several cellular physiological and pathological processes. CK2 is highly expressed in the mammalian brain and catalyzes the phosphorylation of a large number of substrates that are crucial in neuronal or glial homeostasis and inflammatory signaling processes across synapses. In this study, we investigated the impact of auditory integration therapy (AIT) for the treatment of sensory processing abnormalities in autism on plasma CK2 levels. A total of 25 ASD children, aged between 5 and 12 years, were enrolled and participated in the present research study. AIT was performed for two weeks, for a period of 30 min, twice a day, with a 3 h interval between sessions. Before and after AIT, the Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Short Sensory Profile (SSP) scores were calculated, and plasma CK2 levels were assayed using an ELISA test. The CARS and SRS indices of autism severity improved as a result of AIT, which could be related to the decreased level of plasma CK2. However, the mean value of the SSP scores was not significantly increased after AIT. The relationship between CK2 downregulation and glutamate excitotoxicity, neuro-inflammation, and leaky gut, as etiological mechanisms in ASD, was proposed and discussed. Further research, conducted on a larger scale and with a longer study duration, are required to assess whether the cognitive improvement in ASD children after AIT is related to the downregulation of CK2.

Neurodevelopmental dimensional assessment of young children at high genomic risk of neuropsychiatric conditions.

Individuals with 22q11.2 deletion are at considerably increased risk of neurodevelopmental and psychiatric conditions. There have been very few studies investigating how this risk manifests in early childhood and what factors may underlie developmental variability. Insights into this can elucidate transdiagnostic markers of risk that may underlie later development of neuropsychiatric outcomes. Thirty two children with 22q11.2 Deletion Syndrome (22q11.2DS) (mean age=4.1 [SD=1.2] years) and 12 sibling controls (mean age=4.1 [SD=1.5] years) underwent in-depth dimensional phenotyping across several developmental domains selected as being potential early indicators of neurodevelopmental and psychiatric liability. Comparisons were conducted of the dimensional developmental phenotype of 22q11.2DS and sibling controls. For autistic traits, both parents and children were phenotyped using the Social Responsiveness Scale. Young children with 22q11.2DS exhibited large impairments (Hedge's g≥0.8) across a range of developmental domains relative to sibling controls, as well as high rates of transdiagnostic neurodevelopmental and psychiatric traits. Cluster analysis revealed a subgroup of children with 22q11.2DS (n=16; 53%) in whom neurodevelopmental and psychiatric liability was particularly increased and who differed from other children with 22q11.2DS and non-carrier siblings. Exploratory analyses revealed that early motor and sleep impairments indexed liability for neurodevelopmental and psychiatric outcomes. Maternal autism trait scores were predictive of autism traits in children with 22q11.2DS (intraclass correlation coefficients=0.47, p=0.046, n=31). Although psychiatric conditions typically emerge later in adolescence and adulthood in 22q11.2DS, our exploratory study was able to identify a range of early risk indicators. Furthermore, findings indicate the presence of a subgroup who appeared to have increased neurodevelopmental and psychiatric liability. Our findings highlight the scope for future studies of early risk mechanisms and early intervention within this high genetic risk patient group.