Maternal immune activation during pregnancy is associated with more difficulties in socio-adaptive behaviors in autism spectrum disorder.

Autism spectrum disorder (ASD) are neurodevelopmental conditions characterised by deficits in social communication and interaction and repetitive behaviours. Maternal immune activation (MIA) during the mid-pregnancy is a known risk factor for ASD. Although reported in 15% of affected individuals, little is known about the specificity of their clinical profiles. Adaptive skills represent a holistic approach to a person's competencies and reflect specifically in ASD, their strengths and difficulties. In this study, we hypothesised that ASD individual with a history of MIA (MIA+) could be more severely socio-adaptively impaired than those without MIA during pregnancy (MIA-). To answer this question, we considered two independent cohorts of individuals with ASD (PARIS study and FACE ASD) screened for pregnancy history, and used supervised and unsupervised machine learning algorithms. We included 295 mother-child dyads with 14% of them with MIA+. We found that ASD-MIA+ individuals displayed more severe maladaptive behaviors, specifically in their socialization abilities. MIA+ directly influenced individual's socio-adaptive skills, independent of other covariates, including ASD severity. Interestingly, MIA+ affect persistently the socio-adaptive behavioral trajectories of individuals with ASD. The current study has a retrospective design with possible recall bias regarding the MIA event and, even if pooled from two cohorts, has a relatively small population. In addition, we were limited by the number of covariables available potentially impacted socio-adaptive behaviors. Larger prospective study with additional dimensions related to ASD is needed to confirm our results. Specific pathophysiological pathways may explain these clinical peculiarities of ASD- MIA+ individuals, and may open the way to new perspectives in deciphering the phenotypic complexity of ASD and for the development of specific immunomodulatory strategies.

Gender differences in psychosocial function and self-reported health status in late-diagnosed autistic adults: results from the FACE-ASD national cohort.

BACKGROUND: While adult outcome in autism spectrum disorder (ASD) is generally measured using socially valued roles, it could also be understood in terms of aspects related to health status - an approach that could inform on potential gender differences. METHODS: We investigated gender differences in two aspects of outcome related to health-status, i.e. general functioning and self-perceived health status, and co-occurring health conditions in a large multi-center sample of autistic adults. Three hundred and eighty-three participants were consecutively recruited from the FondaMental Advanced Centers of Expertise for ASD cohort (a French network of seven expert centers) between 2013 and 2020. Evaluation included a medical interview, standardized scales for autism diagnosis, clinical and functional outcomes, self-perceived health status and verbal ability. Psychosocial function was measured using the Global Assessment of Functioning scale. RESULTS: While autistic women in this study were more likely than men to have socially valued roles, female gender was associated with poorer physical and mental health (e.g. a 7-fold risk for having three or more co-occurring physical health conditions) and a poorer self-perceived health status. Psychosocial function was negatively associated with depression and impairment in social communication. Half of the sample had multiple co-occurring health conditions but more than 70% reported that their visit at the Expert Center was their first contact with mental health services. CONCLUSIONS: To improve objective and subjective aspects of health outcome, gender differences and a wide range of co-occurring health conditions should be taken into account when designing healthcare provision for autistic adults.

Comparing executive functions profiles in anorexia nervosa and autism spectrum disorder in adolescence.

OBJECTIVE: Executive functions (EFs) inefficiencies in anorexia nervosa (AN), especially in set-shifting and central coherence, suggest a link between AN and autism spectrum disorders (ASDs). This study aimed at comparing EF profiles in AN and ASD, and investigating clinical variables associated with the identified EF difficulties. METHOD: One hundred and sixty-two adolescents with AN or ASD completed self-report questionnaires assessing depression, anxiety and autism symptoms. Parents completed the behaviour rating of executive functions parent-form (BRIEF-P). Besides comparing EFs in AN and ASD, we also analysed clinical variables scoring below and above the mean age score across the all sample. We additionally examined the relationship between clinical variables and the BRIEF-P indexes in AN. RESULTS: Participants with ASD had greater EF difficulties than participants with AN on all BRIEF-P scales. In the whole sample, higher autistic features were related to poorer EF. In AN, lower body mass index and particularly higher autism-spectrum quotient (BRI: Beta = 0.55; p < 0.001 and GEC: Beta = 0.50; p < 0.001) were most strongly associated with poorer EF. CONCLUSION: Although participants with ASD showed greater difficulties, autistic traits were related to alter EFs in AN. Exploring further this dimension can undeniably allow better adaptive cognitive remediation programs.

Rare and de novo duplications containing TCF20 are associated with a neurodevelopmental disorder.

Transcriptor co-activator factor 20 gene (TCF20) encodes a nuclear chromatin-binding protein involved in regulation of gene expression. In human pathology, pathogenic variants or deletions in TCF20 were identified in patients with developmental delay, variable intellectual disability and behavioral impairment (OMIM: 618430). The shared core phenotype includes developmental delay, hypotonia, motor delay, autism spectrum disorders, neurobehavioral anomalies, neurological features such as ataxia, seizures, movement disorders, structural brain anomalies, craniofacial features and various congenital anomalies. Most pathogenic variants are loss-of-function variants. Duplication including TCF20 was suspected to cause a neurodevelopmental disorder (NDD) with mirror traits compared to patients with TCF20 deletions. In the present study, we report three patients from three unrelated families with NDD with a de novo duplication at 22q13.2 encompassing TCF20. We propose that the TCF20 duplication could be involved in a new 22q13.2 microduplication syndrome with high penetrance, enlarging the genotype-phenotype knowledge of TCF20-associated NDDs.

Vestibular Functioning in Children with Neurodevelopmental Disorders Using the Functional Head Impulse Test.

Several studies in children with neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASDs), reading impairment, or attention deficit/hyperactive disorder (ADHD) pointed toward a potential dysfunction of the vestibular system, specifically in its complex relationship with the cerebellum. The aim of the present study was to test the functional vestibulo-ocular reflex (VOR) responses in children with NDDs to measure functional performance of the vestibular system. The VOR is specifically involved in this stabilization of the image on the retina during rapid movements of the head. To perform this study, four groups of children with ASD, ADHD, reading impairment, and with neurotypical development (TD) were enrolled (n = 80). We performed the functional head impulse test (fHIT), which measured the percentage of correct responses by asking the child to identify an optotype briefly presented during passive head impulse in each direction of each semicircular canal plane. We observed significantly lower correct answers in children with NDDs compared with those with TD (p < 0.0001). Surprisingly, there was no significant difference between the three groups of children with NDDs. Our study fostered preliminary evidence suggesting altered efficiency of vestibular system in children with NDDs. VOR abnormalities estimated using the fHIT could be used as a proxy of NDD impairments in children, and represent a potential biomarker.

Short rehabilitation training program may improve postural control in children with autism spectrum disorders: preliminary evidences.

Autism Spectrum Disorders subjects (ASD) is characterized by postural control deficits. This study aimed to explore the effect of a short postural rehabilitation training program on postural capabilities in children with ASD. Two groups (G1 and G2) of twenty children with ASD of IQ-, sex- and age- matched (mean age 11.7 ± 2.4 years) were included in this study. Posture was recorded by using the Balance Quest from Framiral on unstable platform in three different viewing conditions. The rehabilitation program consisted in two distinct postural control training exercises. Postural recordings were performed twice at T1 and T2 for both groups of children. Between T1 and T2 a 6-minute postural training was performed by the G1 group only, while the G2 group had a 6-minute of rest. Children were allocated randomly to the G1 or G2 groups. At T1, postural instability was similar for both groups of ASD children (G1 and G2) desp+\ite viewing conditions. At T2, we observed an improvement of postural control related to a mixed effect of training rehabilitation but also of test-retest. Knowing the potential of new rehabilitation strategies, the impact of postural control deficit in ASD children needs to be reconsidered. Well design case-control studies are requested to ensure scientific validity of postural rehabilitation training program.

Oculomotor behavior in children with autism spectrum disorders.

To identify quantitative indicators of social communication dysfunctions, we explored the oculomotor performances in subjects with autism spectrum disorders. Discordant findings in the literature have been reported for oculomotor behavior in subjects with autism spectrum disorders. This study aimed to explore reflexive and voluntary saccadic performance in a group of 32 children with autism spectrum disorders (mean age: 12.1 ± 0.5 years) compared to 32 age-, sex-, and IQ-matched typically developing children (control group). We used different types of reflexive and voluntary saccades: gap, step, overlap, and anti-saccades. Eye movements were recorded using an eye tracker (Mobile EBT®) and we measured latency, percentage of anticipatory and express saccades, errors of anti-saccades and gain. Children with autism spectrum disorders reported similar latency values with respect to typically developing children for reflexive and voluntary saccades; in contrast, they made more express and anticipatory saccades overall, as shown in paradigm testing (gap, step, overlap, and anti-saccades). Our findings support previous evidence of the atypicality of the cortical network, which is involved in saccade triggering and attentional processes in children with autism spectrum disorders.

Predictive factors for persistent use and compliance of immediate-release methylphenidate: a 36-month naturalistic study.

AIM: The objective of this study was to evaluate predictors of long-term adherence to treatment with methylphenidate (MPH). METHODS: A total of 134 children (ages 4-16) with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) determined by specific protocols, including a semistructured parent interview, Conners' Teacher/Parent Rating Scales, cognitive and learning evaluation, and child self-reports for anxiety and depression, were assessed monthly for up to 36 months. At the end of the study (36 months), three outcomes were evaluated (continuing medication, medication withdrawn due to functional remission, and medication withdrawn for other reasons including poor compliance). Outcomes were first analyzed by mean of the chi-squared test, Mann-Whitney-U test, or t-test, and predictive models were subsequently generated using Cox proportional hazards model analysis. Age, ADHD subtype, co-morbidity, cognitive functioning, side effects, and family and social characteristics were considered as independent variables. RESULTS: Thirty-six months after starting MPH, 62 children (46%) were still on treatment, 32 (24%) had stopped MPH due to functional remission, and 40 (30%) had suspended MPH for other reasons. Within the last group, 20 suspended for poor compliance, 10 for decrease of efficacy, 5 for side effects, and 5 because they entered in an atomoxetine clinical trial. The presence of associated disorders, younger age, female gender, and not living with both parents were predictors for continuing medication until end of the study (36 months); absence of associated disorders and older age were predictors of discontinuation medication due to functional remission before the end of study, older age, and hyperactive subtype were predictors of discontinuing medication for other reasons. CONCLUSION: Clinical outcome of ADHD treatment is heterogeneous: Specific clinical and social predictive parameters for long-term MPH use and compliance can be identified. An accurate tailoring of clinical intervention to the individual child appears crucial for good outcome.