1. Arunachalam Chandran V, Pliatsikas C, Neufeld J, O’Connell G, Haffey A, DeLuca V, Chakrabarti B. Brain structural correlates of autistic traits across the diagnostic divide: A grey matter and white matter microstructure study. NeuroImage Clinical. 2021; 32: 102897.

Autism Spectrum Disorders (ASD) are a set of neurodevelopmental conditions characterised by difficulties in social interaction and communication as well as stereotyped and restricted patterns of interest. Autistic traits exist in a continuum across the general population, whilst the extreme end of this distribution is diagnosed as clinical ASD. While many studies have investigated brain structure in autism using a case-control design, few have used a dimensional approach. To add to this growing body of literature, we investigated the structural brain correlates of autistic traits in a mixed sample of adult participants (25 ASD and 66 neurotypicals; age: 18-60 years). We examined the relationship between regional brain volumes (using voxel-based morphometry and surface-based morphometry) and white matter microstructure properties (using Diffusion Tensor Imaging) and autistic traits (using Autism Spectrum Quotient). Our findings show grey matter differences in regions including the orbitofrontal cortex and lingual gyrus, and suggestive evidence for white matter microstructure differences in tracts including the superior longitudinal fasciculus being related to higher autistic traits. These grey matter and white matter microstructure findings from our study are consistent with previous reports and support the brain structural differences in ASD. These findings provide further support for shared aetiology for autistic traits across the diagnostic divide.

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2. Bar C, Breuillard D, Kuchenbuch M, Jennesson M, Le Guyader G, Isnard H, Rolland A, Doummar D, Fluss J, Afenjar A, Berquin P, De Saint Martin A, Dupont S, Goldenberg A, Lederer D, Lesca G, Maurey H, Meyer P, Mignot C, Nica A, Odent S, Poisson A, Scalais E, Sekhara T, Vrielynck P, Barcia G, Nabbout R. Adaptive behavior and psychiatric comorbidities in KCNB1 encephalopathy. Epilepsy & behavior : E&B. 2022; 126: 108471.

AIM: KCNB1 encephalopathy encompasses a broad phenotypic spectrum associating intellectual disability, behavioral disturbances, and epilepsies of various severity. Using standardized parental questionnaires, we aimed to capture the heterogeneity of the adaptive and behavioral features in a series of patients with KCNB1 pathogenic variants. METHODS: We included 25 patients with a KCNB1 encephalopathy, aged from 3.2 to 34.1 years (median = 10 years). Adaptive functioning was assessed in all patients using the French version of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) questionnaire. We screened global behavior with the Childhood Behavioral Check-List (CBCL, Achenbach) and autism spectrum disorder (ASD) with the Social Communication Questionnaire (SCQ). We used a cluster analysis to identify subgroups of adaptive profiles. RESULTS: VABS-II questionnaire showed pathological adaptive behavior in all participants with a severity of adaptive deficiency ranging from mild in 8/20 to severe in 7/20. Eight out of 16 were at risk of Attention Problems at the CBCL and 13/18 were at risk of autism spectrum disorder (ASD). The adaptive behavior composite score significantly decreased with age (Spearman’s Rho=-0.72, p<0.001) but not the equivalent ages, suggesting stagnation and slowing but no regression over time. The clustering analysis identified two subgroups of patients, one showing more severe adaptive behavior. The severity of the epilepsy phenotype predicted the severity of the behavioral profile with a sensitivity of 70% and a specificity of 90.9%. CONCLUSION: This study confirms the deleterious consequences of early-onset epilepsy in addition to the impact of the gene dysfunction in patients with KCNB1 encephalopathy. ASD and attention disorders are frequent. Parental questionnaires should be considered as useful tools for early screening and care adaptation.

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3. Bilge S, Ekici B. CBD-enriched cannabis for autism spectrum disorder: an experience of a single center in Turkey and reviews of the literature. Journal of cannabis research. 2021; 3(1): 53.

INTRODUCTION: Autism spectrum disorder is a neurodevelopmental disorder characterized by deficits in communication, social interaction, restricted interest, and repetitive behaviors. Although more cases are being diagnosed, no drugs are approved to treat the core symptoms or cognitive and behavioral problems associated with autism. Therefore, there is an urgent need to develop an effective and safe treatment. OBJECTIVE: In this study, we aim to share our 2-year experience with CBD-enriched cannabis treatment in autism and review the latest studies. MATERIALS AND METHODS: The study included 33 (27 males, six females) children diagnosed with autism spectrum disorder who were followed up between January 2018 and August 2020. The mean age was 7.7 ± 5.5 years. The average daily dosage of cannabidiol (CBD) was 0.7 mg/kg/day (0.3-2 mg/kg/day). The median duration of treatment was 6.5 months (3-28 months). The preparations used in this study contained full-spectrum CBD and trace elements tetrahydrocannabinol (THC) of less than 3%. RESULTS: The outcomes were evaluated before and after treatment based on clinical interviews. At each follow-up visit, parents were asked to evaluate the effectiveness of the CBD-enriched cannabis treatment. According to the parents’ reports, no change in daily life activity was reported in 6 (19.35%) patients. The main improvements of the treatment were as follows: a decrease in behavioral problems was reported in 10 patients (32.2%), an increase in expressive language was reported in 7 patients (22.5%), improved cognition was reported in 4 patients (12,9%), an increase in social interaction was reported in 3 patients (9.6%), and a decrease in stereotypes was reported in 1 patient (3.2%). The parents reported improvement in cognition among patients who adhered to CBD-enriched cannabis treatment for over two years. The antipsychotic drug could be stopped only in one patient who showed mild ASD symptoms. No change could be made in other drug use and doses. Additionally, this study includes an extensive review of the literature regarding CBD treatment in autism spectrum disorder. According to recent studies, the average dose of CBD was 3.8±2.6 mg/kg/day. The ratio of CBD to THC in the used preparations was 20:1. The most significant improvements were seen in the behavioral problems reported in 20-70% of the patients. CONCLUSION: Using lower doses of CBD and trace THC seems to be promising in managing behavioral problems associated with autism. In addition, this treatment could be effective in managing the core symptoms and cognitive functions. No significant side effects were seen at the low doses of CBD-enriched cannabis when compared to other studies.

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4. Boyd BA, Stahmer AC, Odom SL, Wallisch A, Matheis M. It’s time to close the research to practice gap in autism: The need for implementation science. Autism : the international journal of research and practice. 2022; 26(3): 569-74.

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5. Cui J, Park J, Ju X, Lee Y, Hong B, Ahn J, Kim YH, Ko Y, Yoon SH, Lim C, Lee SY, Huh SO, Heo JY, Chung W. General Anesthesia During Neurodevelopment Reduces Autistic Behavior in Adult BTBR Mice, a Murine Model of Autism. Frontiers in cellular neuroscience. 2021; 15: 772047.

Preclinical studies suggest that repeated exposure to anesthetics during a critical period of neurodevelopment induces long-term changes in synaptic transmission, plasticity, and behavior. Such changes are of great concern, as similar changes have also been identified in animal models of neurodevelopmental disorders (NDDs) such as autism. Because of overlapping synaptic changes, it is also possible that anesthetic exposures have a more significant effect in individuals diagnosed with NDDs. Thus, we evaluated the effects of early, multiple anesthetic exposures in BTBR mice, an inbred strain that displays autistic behavior. We discovered that three cycles of sevoflurane anesthesia (2.5%, 1 h) with 2-h intervals between each exposure in late postnatal BTBR mice did not aggravate, but instead improved pathophysiological mechanisms involved with autistic behavior. Sevoflurane exposures restored E/I balance (by increasing inhibitory synaptic transmission), and increased mitochondrial respiration and BDNF signaling in BTBR mice. Most importantly, such changes were associated with reduced autistic behavior in BTBR mice, as sociability was increased in the three-chamber test and repetitive behavior was reduced in the self-grooming test. Our results suggest that anesthetic exposures during neurodevelopment may affect individuals diagnosed with NDDs differently.

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6. Dow D, Holbrook A, Toolan C, McDonald N, Sterrett K, Rosen N, Kim SH, Lord C. The Brief Observation of Symptoms of Autism (BOSA): Development of a New Adapted Assessment Measure for Remote Telehealth Administration Through COVID-19 and Beyond. Journal of autism and developmental disorders. 2021: 1-12.

Interest in telehealth assessment for autism has increased due to COVID-19 and subsequent expansion of remote psychological services, though options that are easy for clinicians to adopt and available through the lifespan are limited. The Brief Observation of Symptoms of Autism (BOSA) provides a social context with standardized materials and activities that can be coded by clinicians trained in the Autism Diagnostic Observation Schedule. The current project examined psychometric properties to determine optimal use for each BOSA version. Three hundred and seven participants with 453 BOSAs were included to determine best performing items for algorithms, validity, sensitivity, specificity, recommended cut-offs, and proposed ranges of concern. While preliminary, the BOSA provides a promising new option for telehealth-administered assessment for autism.

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7. Hamid R, Sant HS, Kulkarni MN. Choline Transporter regulates olfactory habituation via a neuronal triad of excitatory, inhibitory and mushroom body neurons. PLoS genetics. 2021; 17(12): e1009938.

Choline is an essential component of Acetylcholine (ACh) biosynthesis pathway which requires high-affinity Choline transporter (ChT) for its uptake into the presynaptic terminals of cholinergic neurons. Previously, we had reported a predominant expression of ChT in memory processing and storing region of the Drosophila brain called mushroom bodies (MBs). It is unknown how ChT contributes to the functional principles of MB operation. Here, we demonstrate the role of ChT in Habituation, a non-associative form of learning. Odour driven habituation traces are laid down in ChT dependent manner in antennal lobes (AL), projection neurons (PNs), and MBs. We observed that reduced habituation due to knock-down of ChT in MBs causes hypersensitivity towards odour, suggesting that ChT also regulates incoming stimulus suppression. Importantly, we show for the first time that ChT is not unique to cholinergic neurons but is also required in inhibitory GABAergic neurons to drive habituation behaviour. Our results support a model in which ChT regulates both habituation and incoming stimuli through multiple circuit loci via an interplay between excitatory and inhibitory neurons. Strikingly, the lack of ChT in MBs shows characteristics similar to the major reported features of Autism spectrum disorders (ASD), including attenuated habituation, sensory hypersensitivity as well as defective GABAergic signalling. Our data establish the role of ChT in habituation and suggest that its dysfunction may contribute to neuropsychiatric disorders like ASD.

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8. Ho FK, Rao N, Tung KTS, Wong RS, Wong WHS, Tung JYL, Chua GT, Tso WWY, Bacon-Shone J, Wong ICK, Yousafzai A, Wright C, Ip P. Association of Early Nutritional Status With Child Development in the Asia Pacific Region. JAMA network open. 2021; 4(12): e2139543.

IMPORTANCE: Stunting was used as a proxy for underdevelopment in early childhood in previous studies, but the associations between child development and other growth and body composition parameters were rarely studied. OBJECTIVE: To estimate the association between malnutrition and early child development (ECD) at an individual level. DESIGN, SETTING, AND PARTICIPANTS: This population-based, cross-sectional study used data from the East Asia Pacific Early Child Development Scales, a population-representative survey of children aged 3 to 5 years old, conducted in 2012 to 2014 in communities in Cambodia, China, Mongolia, Papua New Guinea, and Vanuatu. Data analysis was performed from November 2019 to April 2021. EXPOSURES: Stunting (height-for-age [HFA] z score less than -2), wasting (weight-for-height z score less than -2), overweight (weight-for-height z score greater than 2), body mass index (BMI)-for-age z score, and body fat proportion based on existing growth standard and formula. MAIN OUTCOMES AND MEASURES: ECD directly assessed using the validated East Asia-Pacific ECD Scales. RESULTS: A total of 7108 children (3547 girls; mean [SD], age 4.48 [0.84] years) were included in this study. The prevalence of stunting was 27.1% (range across countries, 1.2%-55.0%), that of wasting was 13.7% (range, 5.4%-35.9%), and that of overweight was 15.9% (range, 2.2%-53.7%). Adjusted for country variations, age, sex, urbanicity, family socioeconomic status, and body fat proportion, ECD was linearly associated with HFA (β, 1.57; 95% CI, 1.35-1.80) and BMI-for-age (β, 0.64; 95% CI, 0.45-0.82). After adjustment for BMI and height, better ECD was associated with low body fat proportion (β, 0.93; 95% CI, 0.45-1.42). The association of HFA was more pronounced in Southeast Asia and the Pacific region than in East Asia, and the association of fat proportion was specific to children living in urban environments. CONCLUSIONS AND RELEVANCE: HFA, BMI-for-age, and body fat proportion were independently associated with ECD, and these findings suggest that future studies should consider using these parameters to estimate the prevalence of child underdevelopment; nutritional trials should examine to what extent the associations are causal.

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9. Jassi AD, Vidal-Ribas P, Krebs G, Mataix-Cols D, Monzani B. Examining clinical correlates, treatment outcomes and mediators in young people with comorbid obsessive-compulsive disorder and autism spectrum disorder. European child & adolescent psychiatry. 2021.

Despite the high comorbidity, surprisingly little is known about the clinical features, treatment prognosis, and treatment mediators for youth with Obsessive-Compulsive Disorder (OCD) and Autism Spectrum Disorder (ASD). This study, the largest to date, compared 172 young people with OCD and ASD (OCD + ASD) to 447 without ASD (OCD) on clinical characteristics, finding those with OCD + ASD were more likely to endorse poorer insight into their OCD, have greater global functional impairment, greater levels of concurrent psychopathology, higher levels of family accommodation and to be on medication. Treatment outcomes following a course of Cognitive Behaviour Therapy with or without medication were explored for a subgroup; 100 young people with OCD + ASD and 223 with OCD. Whilst both groups benefitted from treatment, the OCD + ASD group had significantly poorer treatment outcomes. Greater global functional impairment and being on medication mediated the between-group difference in outcomes. Further research and treatment refinements are needed to improve outcomes for youth with OCD + ASD.

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10. Kang QQ, Li X, Tong GL, Fan YL, Shi L. Magnetic resonance spectroscopy features of the thalamus and the cerebellum and their association with clinical features in children with autism spectrum disorder: a prospective study. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics. 2021; 23(12): 1250-5.

OBJECTIVES: To study the changes in biochemical metabolites in the thalamus and the cerebellum and their association with clinical features in children with autism spectrum disorder (ASD). METHODS: In this prospective study, magnetic resonance spectroscopy (MRS) with point-resolved spatial selection was used to analyze the thalamus and the cerebellum at both sides in 50 children with ASD aged 2-6 years. Creatine (Cr) was as the internal standard to measure the relative values of N-acetylaspartate (NAA)/Cr, choline (Cho)/Cr, myoinositol (MI)/Cr, and glutamine and glutamate complex (Glx)/Cr, and the differences in metabolites and their association with clinical symptoms were compared. RESULTS: In the children with ASD, NAA/Cr in the left thalamus was positively correlated with the scores of hearing-language and hand-eye coordination in the Griffiths Development Scales-Chinese (P<0.05). Cho/Cr in the right cerebellum was positively correlated with the scores of personal-social competence, hearing-language, and hand-eye coordination (P<0.05). NAA/Cr and Glx/Cr in the left thalamus were positively correlated with those in the left cerebellum (P<0.05). There was no significant difference in metabolites between the left and right sides of the thalamus and the cerebellum in the children with ASD (P>0.05). CONCLUSIONS: There are metabolic disorders in the cerebellum and the thalamus in children with ASD, and there is a correlation between the changes of metabolites in the left cerebellum and the left thalamus. Some metabolic indexes are related to the clinical symptoms of ASD. MRS may reveal the pathological basis of ASD and provide a basis for diagnosis and prognosis assessment of ASD as a noninvasive and quantitative detection method. OBJECTIVE: To study the changes in biochemical metabolites in the thalamus and the cerebellum and their association with clinical features in children with autism spectrum disorder (ASD). METHODS: In this prospective study, magnetic resonance spectroscopy (MRS) with point-resolved spatial selection was used to analyze the thalamus and the cerebellum at both sides in 50 children with ASD aged 2-6 years. Creatine (Cr) was as the internal standard to measure the relative values of N-acetylaspartate (NAA)/Cr, choline (Cho)/Cr, myoinositol (MI)/Cr, and glutamine and glutamate complex (Glx)/Cr, and the differences in metabolites and their association with clinical symptoms were compared. RESULTS: In the children with ASD, NAA/Cr in the left thalamus was positively correlated with the scores of hearing-language and hand-eye coordination in the Griffiths Development Scales-Chinese (P<0.05). Cho/Cr in the right cerebellum was positively correlated with the scores of personal-social competence, hearing-language, and hand-eye coordination (P<0.05). NAA/Cr and Glx/Cr in the left thalamus were positively correlated with those in the left cerebellum (P<0.05). There was no significant difference in metabolites between the left and right sides of the thalamus and the cerebellum in the children with ASD (P>0.05). CONCLUSIONS: There are metabolic disorders in the cerebellum and the thalamus in children with ASD, and there is a correlation between the changes of metabolites in the left cerebellum and the left thalamus. Some metabolic indexes are related to the clinical symptoms of ASD. MRS may reveal the pathological basis of ASD and provide a basis for diagnosis and prognosis assessment of ASD as a noninvasive and quantitative detection method. eng.

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11. Mason L, Shic F, Falck-Ytter T, Chakrabarti B, Charman T, Loth E, Tillmann J, Banaschewski T, Baron-Cohen S, Bölte S, Buitelaar J, Durston S, Oranje B, Persico AM, Beckmann C, Bougeron T, Dell’Acqua F, Ecker C, Moessnang C, Murphy D, Johnson MH, Jones EJH. Preference for biological motion is reduced in ASD: implications for clinical trials and the search for biomarkers. Molecular autism. 2021; 12(1): 74.

BACKGROUND: The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology. METHODS: Eye-tracking data were collected from 486 6-to-30-year-old autistic (N = 282) and non-autistic control (N = 204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL). RESULTS: The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline. LIMITATIONS: The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons. CONCLUSIONS: Biological motion preference elicits small-to-medium-sized case-control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear.

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12. Musi CA, Castaldo AM, Valsecchi AE, Cimini S, Morello N, Pizzo R, Renieri A, Meloni I, Bonati M, Giustetto M, Borsello T. JNK signaling provides a novel therapeutic target for Rett syndrome. BMC biology. 2021; 19(1): 256.

BACKGROUND: Rett syndrome (RTT) is a monogenic X-linked neurodevelopmental disorder characterized by loss-of-function mutations in the MECP2 gene, which lead to structural and functional changes in synapse communication, and impairments of neural activity at the basis of cognitive deficits that progress from an early age. While the restoration of MECP2 in animal models has been shown to rescue some RTT symptoms, gene therapy intervention presents potential side effects, and with gene- and RNA-editing approaches still far from clinical application, strategies focusing on signaling pathways downstream of MeCP2 may provide alternatives for the development of more effective therapies in vivo. Here, we investigate the role of the c-Jun N-terminal kinase (JNK) stress pathway in the pathogenesis of RTT using different animal and cell models and evaluate JNK inhibition as a potential therapeutic approach. RESULTS: We discovered that the c-Jun N-terminal kinase (JNK) stress pathway is activated in Mecp2-knockout, Mecp2-heterozygous mice, and in human MECP2-mutated iPSC neurons. The specific JNK inhibitor, D-JNKI1, promotes recovery of body weight and locomotor impairments in two mouse models of RTT and rescues their dendritic spine alterations. Mecp2-knockout presents intermittent crises of apnea/hypopnea, one of the most invalidating RTT pathological symptoms, and D-JNKI1 powerfully reduces this breathing dysfunction. Importantly, we discovered that also neurons derived from hiPSC-MECP2 mut show JNK activation, high-phosphorylated c-Jun levels, and cell death, which is not observed in the isogenic control wt allele hiPSCs. Treatment with D-JNKI1 inhibits neuronal death induced by MECP2 mutation in hiPSCs mut neurons. CONCLUSIONS: As a summary, we found altered JNK signaling in models of RTT and suggest that D-JNKI1 treatment prevents clinical symptoms, with coherent results at the cellular, molecular, and functional levels. This is the first proof of concept that JNK plays a key role in RTT and its specific inhibition offers a new and potential therapeutic tool to tackle RTT.

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13. Nadeem A, Ahmad SF, Al-Harbi NO, Al-Ayadhi LY, Sarawi W, Attia SM, Bakheet SA, Alqarni SA, Ali N, AsSobeai HM. Imbalance in pro-inflammatory and anti-inflammatory cytokines milieu in B cells of children with autism. Molecular immunology. 2022; 141: 297-304.

B cells play multiple roles in preservation of healthy immune system including management of immune responses by expression of pro- and anti-inflammatory cytokines. Several earlier studies have documented that B cells express both pro-inflammatory cytokines such as IL-6, TNF-α as well as anti-inflammatory cytokines such as IL-10. However, it is yet to be examined whether these pro-/anti-inflammatory cytokines are expressed in B cells of children with autism spectrum disorder (ASD). Pathophysiology of ASD begins in early childhood and is characterized by repetitive/restricted behavioral patterns, and dysfunction in communal/communication skills. ASD pathophysiology also has a strong component of immune dysfunction which has been highlighted in numerous earlier publications. In this study, we specifically explored pro-/anti-inflammatory cytokines (IL-6, IL-17A, IFN-γ, TNF-α, IL-10) in B cells of ASD subjects and compared them typically developing control (TDC) children. Present study shows that inflammatory cytokines such as IL-6 and TNF-α are elevated in B cells of ASD subjects, while anti-inflammatory cytokine, IL-10 is decreased in ASD group when compared to TDC group. Further, TLR4 activation by its ligand, lipopolysaccharide (LPS) further upregulates inflammatory potential of B cells from ASD group by increasing IL-6 expression, whereas LPS has no significant effect on IL-10 expression in ASD group. Furthermore, LPS-induced inflammatory signaling of IL-6 in B cells of ASD subjects was partially mitigated by the pretreatment with NF-kB inhibitor. Present study propounds the idea that B cells could be crucial players in causing immune dysfunction in ASD subjects through an imbalance in expression of pro-/anti-inflammatory cytokines.

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14. Ptomey LT, Lee J, White DA, Helsel BC, Washburn RA, Donnelly JE. Changes in physical activity across a 6-month weight loss intervention in adolescents with intellectual and developmental disabilities. Journal of intellectual disability research : JIDR. 2021.

BACKGROUND: Adolescents and young adults with intellectual and developmental disabilities (IDD) have high rates of obesity and low levels of physical activity. This analysis examined changes in light, moderate-to-vigorous physical activity (MVPA) and sedentary time, and the association between changes in MVPA and weight loss in adolescents and young adults with IDD and overweight and obesity participating in a 6-month multi-component weight loss intervention. METHODS: Adolescents and young adults with IDD and overweight or obesity (body mass index ≥ 85 percentile, n = 110, age ~16 years, 52.7% female) and a parent were randomised to one of three intervention groups: face-to-face delivery/conventional reduced energy diet (n = 36), remote delivery (RD)/conventional reduced energy diet (n = 39), or RD/reduced energy enhanced stop light diet (eSLD) (n = 35.) Participants were asked to engage in 60 min/day of MVPA on 5 or more days/wk. Participants and a parent attended twice monthly education/behavioural counselling sessions with a health educator to assist participants in complying with dietary and MVPA recommendations. Education/counselling in the RD arms was delivered remotely using video conferencing, and self-monitoring of MVPA and daily steps was completed using a wireless activity tracker. Education/counselling in the face-to-face arm was delivered during home-visits and self-monitoring of MVPA and daily steps was completed by self-report using paper tracking forms designed for individuals with IDD. MVPA, light activity, and sedentary time were assessed over 7 days at baseline and 6 months using a portable accelerometer (ActiGraph wGT3x-BT). RESULTS: Mixed modelling analysis completed using participants with valid accelerometer data (i.e. ≥4-10 h days) at baseline (n = 68) and 6 months (n = 30) revealed no significant changes in light, moderate- MVPA, or sedentary time across the 6-month intervention (all P > 0.05). Participants obtained 15.2 ± 21.5 min/day of MVPA at baseline and 19.7 ± 19.7 min/day at 6 months (P = 0.119). Mixed modelling indicated no significant effects of group (P = 0.79), time (P = 0.10), or group-by-time interaction (P = 0.21) on changes in MVPA from baseline to 6 months. Correlational analysis conducted on participants with valid accelerometer data at both baseline and 6 months (n = 24) revealed no significant associations between baseline sedentary time (r = 0.10, P = 0.40) and baseline MVPA (r = -0.22, P = 0.30) and change in MVPA across the 6-month intervention. Additionally, attendance at education/counselling sessions (r = 0.26, P = 0.22) and frequency of self-monitoring of MVPA were not significantly associated with change in MVPA from baseline to 6 months (r = 0.26, P = 0.44). Baseline MVPA (r = 0.02, P = 0.92) and change in MVPA from baseline to 6 months (r = 0.13, P = 0.30) were not associated with changes in body weight across the 6-month intervention. CONCLUSION: We observed a non-significant increase in MVPA (30%), which was not associated with the magnitude of weight loss in a sample of adolescents and young adults with IDD who participated in a 6-month multi-component weight loss intervention. Additional strategies to increase MVPA in adolescents and young adults with IDD participating in weight loss interventions need to be developed and evaluated.

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15. Valenza M, Steardo L, Jr., Steardo L, Verkhratsky A, Scuderi C. Systemic Inflammation and Astrocyte Reactivity in the Neuropsychiatric Sequelae of COVID-19: Focus on Autism Spectrum Disorders. Frontiers in cellular neuroscience. 2021; 15: 748136.

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16. Wei C, Sun M, Sun X, Meng H, Li Q, Gao K, Yue W, Wang L, Zhang D, Li J. RhoGEF Trio Regulates Radial Migration of Projection Neurons via Its Distinct Domains. Neuroscience bulletin. 2022; 38(3): 249-62.

The radial migration of cortical pyramidal neurons (PNs) during corticogenesis is necessary for establishing a multilayered cerebral cortex. Neuronal migration defects are considered a critical etiology of neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia, epilepsy, and intellectual disability (ID). TRIO is a high-risk candidate gene for ASDs and ID. However, its role in embryonic radial migration and the etiology of ASDs and ID are not fully understood. In this study, we found that the in vivo conditional knockout or in utero knockout of Trio in excitatory precursors in the neocortex caused aberrant polarity and halted the migration of late-born PNs. Further investigation of the underlying mechanism revealed that the interaction of the Trio N-terminal SH3 domain with Myosin X mediated the adherence of migrating neurons to radial glial fibers through regulating the membrane location of neuronal cadherin (N-cadherin). Also, independent or synergistic overexpression of RAC1 and RHOA showed different phenotypic recoveries of the abnormal neuronal migration by affecting the morphological transition and/or the glial fiber-dependent locomotion. Taken together, our findings clarify a novel mechanism of Trio in regulating N-cadherin cell surface expression via the interaction of Myosin X with its N-terminal SH3 domain. These results suggest the vital roles of the guanine nucleotide exchange factor 1 (GEF1) and GEF2 domains in regulating radial migration by activating their Rho GTPase effectors in both distinct and cooperative manners, which might be associated with the abnormal phenotypes in neurodevelopmental disorders.

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17. Xie Y, Jin Z, Huang H, Li S, Dong G, Liu Y, Chen G, Guo Y. Outdoor light at night and autism spectrum disorder in Shanghai, China: A matched case-control study. The Science of the total environment. 2022; 811: 152340.

BACKGROUND: Several environmental factors have been identified to be associated with autism spectrum disorder (ASD) over the past decades. However, evidence is limited for the effect of exposure to outdoor light at night (LAN) on ASD in China and even elsewhere in the world. METHODS: Participants in this study were from a multi-stage sampling survey on ASD conducted between June 2014 and October 2014 among children aged 3-12 years in Shanghai, China. All participants underwent a two-stage screening of ASD via questionnaire, and then, suspected cases were finally diagnosed by clinical examination. For data analyses, each ASD case was randomly matched with 10 healthy controls by age and sex. The LAN data were extracted from the stable lights product of the US Defense Meteorological Satellite Program’s Operational Linescan System (DMSP-OLS) according to geolocation information of residential addresses. Mean levels of exposure to LAN during the 3 years after birth and 1 year before birth were calculated. We used conditional logistic regression models to examine the association between LAN and ASD. RESULTS: We investigated 84,934 children from 96 kindergartens, 55 primary schools, and 28 special education schools, and 203 children were diagnosed as ASD cases. A total of 1727 children (157 ASD cases and 1570 healthy controls) were included in the final analyses. Brighter LAN exposures after and before birth were significantly associated with higher risk of ASD. After adjusting for potential covariates, adjusted odd ratios and 95% confidence intervals associated with per unit increase in LAN were 1.066 (1.027, 1.107) during the 3 years after birth and 1.046 (1.018, 1.075) during the 1 year before birth. CONCLUSIONS: Results of our study concluded brighter LAN exposure was significantly associated with higher risk of ASD among Chinese children, which suggested that outdoor LAN could be a potential risk factor of ASD.

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18. Yankowitz LD, Yerys BE, Herrington JD, Pandey J, Schultz RT. Dissociating regional gray matter density and gray matter volume in autism spectrum condition. NeuroImage Clinical. 2021; 32: 102888.

BACKGROUND: Despite decades of research, there is continued uncertainty regarding whether autism is associated with a specific profile of gray matter (GM) structure. This inconsistency may stem from the widespread use of voxel-based morphometry (VBM) methods that combine indices of GM density and GM volume. If GM density or volume, but not both, prove different in autism, the traditional VBM approach of combining the two indices may obscure the difference. The present study measures GM density and volume separately to examine whether autism is associated with alterations in GM volume, density, or both. METHODS: Differences in MRI-based GM density and volume were examined in 6-25 year-olds with a diagnosis of autism spectrum disorder (n = 213, 80.8% male, IQ 47-154) and a typically developing (TD) sample (n = 190, 71.6% male, IQ 67-155). High-resolution T1-weighted anatomical images were collected on a single MRI scanner. Regional density and volume were estimated via whole-brain parcellation comprised of 1625 parcels. Parcel-wise analyses were conducted using generalized additive models while controlling the false discovery rate (FDR, q < 0.05). Volume differences in the 68-region Desikan-Killiany atlas derived from Freesurfer were also examined, to establish the generalizability of findings across methods. RESULTS: No density differences were observed between the autistic and TD groups, either in individual parcels or whole brain mean density. Increased volume was observed in autism compared to the TD group when controlling for Age, Sex, and IQ, both at the level of the whole brain (total volume) and in 45 parcels (2.8% of total parcels). Parcels with greater volume included inferior, middle, and superior temporal gyrus, inferior and superior frontal gyrus, precuneus, and fusiform gyrus. Converging evidence from a standard Freesurfer pipeline also identified greater volume in a number of overlapping regions. LIMITATIONS: The method for determining "density" is not a direct measure of neuronal density, and this study cannot reveal underlying cellular differences. While this study represents possibly the largest single-site sample of its kind, it is underpowered to detect very small differences. CONCLUSIONS: These results provide compelling evidence that autism is associated with regional GM volumetric differences, which are more prominent than density differences. This underscores the importance of examining volume and density separately, and suggests that direct measures of volume (e.g. region-of-interest or tensor-based morphometry approaches) may be more sensitive to autism-relevant differences in neuroanatomy than concentration/density-based approaches.

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19. Zhang YR, Tao HM, Yang G, Wang Y, Sha L, Shao Z. Efficacy of family rehabilitation treatment performed by parents under the guidance of professionals in children with autism spectrum disorder: a prospective study. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics. 2021; 23(12): 1256-61.

OBJECTIVES: To study the efficacy of family rehabilitation treatment performed by parents under the guidance of professionals in children with autism spectrum disorder (ASD). METHODS: In the prospective study, 60 children with ASD, aged 24-60 months, were randomly divided into an observation group and a conventional group. The parents of the children in the conventional group received an online training on basic knowledge and rehabilitation training of ASD alone, and those in the observation group received the online training and performed family rehabilitation treatment under the guidance of a professional team. Psycho-Education Profile Third Edition (PEP-3) and Childhood Autism Rating Scale (CARS) were used to evaluate the changes in related abilities after intervention. RESULTS: After 6 months of intervention, the scores of all dimensions of the PEP-3 scale in the observation group and most dimensions of the conventional group significantly increased (P<0.01); the CARS scale scores of the two groups significantly decreased (P<0.05). Compared with the conventional group, the observation group had significant increases in the scores of the dimensions of language understanding, language expression, gross motor, fine motor, self-care ability of daily living (P<0.05), and adaptive behavior (P<0.05), as well as a significant reduction in the CARS score (P<0.05). CONCLUSIONS: An online training on basic knowledge and rehabilitation training of ASD for parents can improve the abilities and core clinical symptoms of children with ASD. The family rehabilitation treatment model with a team of professionals as the resource platform and parents as the performer has a more significant efficacy on improving the language, sports, and other abilities and alleviating the severity of the symptoms in children with ASD. OBJECTIVE: To study the efficacy of family rehabilitation treatment performed by parents under the guidance of professionals in children with autism spectrum disorder (ASD). METHODS: In the prospective study, 60 children with ASD, aged 24-60 months, were randomly divided into an observation group and a conventional group. The parents of the children in the conventional group received an online training on basic knowledge and rehabilitation training of ASD alone, and those in the observation group received the online training and performed family rehabilitation treatment under the guidance of a professional team. Psycho-Education Profile Third Edition (PEP-3) and Childhood Autism Rating Scale (CARS) were used to evaluate the changes in related abilities after intervention. RESULTS: After 6 months of intervention, the scores of all dimensions of the PEP-3 scale in the observation group and most dimensions of the conventional group significantly increased (P<0.01); the CARS scale scores of the two groups significantly decreased (P<0.05). Compared with the conventional group, the observation group had significant increases in the scores of the dimensions of language understanding, language expression, gross motor, fine motor, self-care ability of daily living (P<0.05), and adaptive behavior (P<0.05), as well as a significant reduction in the CARS score (P<0.05). CONCLUSIONS: An online training on basic knowledge and rehabilitation training of ASD for parents can improve the abilities and core clinical symptoms of children with ASD. The family rehabilitation treatment model with a team of professionals as the resource platform and parents as the performer has a more significant efficacy on improving the language, sports, and other abilities and alleviating the severity of the symptoms in children with ASD. eng.

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