The impact of antidepressants on human neurodevelopment: Brain organoids as experimental tools.

The use of antidepressants during pregnancy benefits the mother's well-being, but the effects of such substances on neurodevelopment remain poorly understood. Moreover, the consequences of early exposure to antidepressants may not be immediately apparent at birth. In utero exposure to selective serotonin reuptake inhibitors (SSRIs) has been related to developmental abnormalities, including a reduced white matter volume. Several reports have observed an increased incidence of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) after prenatal exposure to SSRIs such as sertraline, the most widely prescribed SSRI. The advent of human-induced pluripotent stem cell (hiPSC) methods and assays now offers appropriate tools to test the consequences of such compounds for neurodevelopment in vitro. In particular, hiPSCs can be used to generate cerebral organoids - self-organized structures that recapitulate the morphology and complex physiology of the developing human brain, overcoming the limitations found in 2D cell culture and experimental animal models for testing drug efficacy and side effects. For example, single-cell RNA sequencing (scRNA-seq) and electrophysiological measurements on organoids can be used to evaluate the impact of antidepressants on the transcriptome and neuronal activity signatures in developing neurons. While the analysis of large-scale transcriptomic data depends on dimensionality reduction methods, electrophysiological recordings rely on temporal data series to discriminate statistical characteristics of neuronal activity, allowing for the rigorous analysis of the effects of antidepressants and other molecules that affect the developing nervous system, especially when applied in combination with relevant human cellular models such as brain organoids.

Temporal manipulation of the Scn1a gene reveals its essential role in adult brain function.

Dravet syndrome is a severe epileptic encephalopathy, characterized by drug-resistant epilepsy, severe cognitive and behavioural deficits, with increased risk of sudden unexpected death (SUDEP). It is caused by haploinsufficiency of SCN1A gene encoding for the α-subunit of the voltage-gated sodium channel Nav1.1. Therapeutic approaches aiming to upregulate the healthy copy of SCN1A gene to restore its normal expression levels are being developed. However, whether Scn1a gene function is required only during a specific developmental time-window or, alternatively, if its physiological expression is necessary in adulthood is untested up to now. We induced Scn1a gene haploinsufficiency at two ages spanning postnatal brain development (P30 and P60) and compared the phenotypes of those mice to Scn1a perinatally induced mice (P2), recapitulating all deficits of Dravet mice. Induction of heterozygous Nav1.1 mutation at P30 and P60 elicited susceptibility to the development of both spontaneous and hyperthermia-induced seizures and SUDEP rates comparable to P2-induced mice, with symptom onset accompanied by the characteristic GABAergic interneuron dysfunction. Finally, delayed Scn1a haploinsufficiency induction provoked hyperactivity, anxiety and social attitude impairment at levels comparable to age matched P2-induced mice, while it was associated with a better cognitive performance, with P60-induced mice behaving like the control group. Our data show that maintenance of physiological levels of Nav1.1 during brain development is not sufficient to prevent Dravet symptoms and that long-lasting restoration of Scn1a gene expression would be required to grant optimal clinical benefit in patients with Dravet syndrome.

Enhanced neural synchronization during social communications between dyads with high autistic traits.

Autism is characterized by atypical social communication styles. To investigate whether individuals with high autistic traits could still have effective social communication among each other, we compared the behavioral patterns and communication quality within 64 dyads of college students paired with both high, both low, and mixed high-low (HL) autistic traits, with their gender matched. Results revealed that the high-high (HH) autistic dyads exhibited atypical behavioral patterns during conversations, including reduced mutual gaze, communicational turns, and emotional sharing compared with the low-low and/or HL autistic dyads. However, the HH autistic dyads displayed enhanced interpersonal neural synchronization during social communications measured by functional near-infrared spectroscopy, suggesting an effective communication style. Besides, they also provided more positive subjective evaluations of the conversations. These findings highlight the potential for alternative pathways to effectively communicate with the autistic community, contribute to a deeper understanding of how high autistic traits influence social communication dynamics among autistic individuals, and provide important insights for the clinical practices for supporting autistic people.

High autistic traits linked with reduced performance on affective task switching: An ERP study.

Few studies have investigated affective flexibility in individuals with high autistic traits. In the present study, we employed affective task-switching paradigm combined with event related potential (ERP) technology to explore affective flexibility in individuals with high autistic traits. Participants were instructed to switch between identifying the gender (gender task) and emotion (emotion task) of presented faces. Two groups of participants were recruited based on the Autism Spectrum Quotient (AQ) scores: a High Autistic Group (HAG) and a Low Autistic Group (LAG). The results confirmed that the HAG exhibited greater behavioral emotion switch costs and increased N2 and decreased P3 components when switching to the emotion task. Additionally, we identified an affective asymmetric switch cost in the HAG, where the switch cost for the emotion task was larger than for the gender task at both behavioral and electrophysiological levels. In contrast, a symmetrical switch cost was observed in the LAG. These findings indicate that the HAG experiences difficulties with affective flexibility, particularly in tasks involving emotional processing. The patterns of affective asymmetric switch costs observed in both groups differed from previous results in autistic children and the general population, suggesting that the relative dominance of gender and emotion tasks may vary between the two groups. We propose that the dominance of emotion tasks declines as autistic traits increase.

Critical period of exposure to mercury and the diagnostic of autism spectrum disorder: A systematic review.

Autism spectrum disorder (ASD) is characterized by repetitive behaviors and deficits in social interaction. Its etiology is not completely clear, but both genetic and environmental factors contribute to and influence its development and course. The increased number of autism cases in recent years has been strongly associated with increased exposure to heavy metals. Mercury (Hg) has gained prominence in the scientific literature as a result of its presence as an urban pollutant and well-described neurotoxicity. This review assessed the relationship between Hg exposure in the pre- and post-natal period and ASD. The systematic review identified observational clinical studies and pre-clinical trials in journals indexed in the PubMed, Embase, ProQuest, and LILACS databases. The aim of this study was to investigate the association between exposure to Hg and ASD and to define the critical period of exposure. A total of 57 articles were selected for this review, with 35 articles (61.40%) identifying a positive association between ASD and Hg, while 22 articles (38.60%) did not find the same outcome. The biological samples most used to analyze Hg body burdens were hair (36.84%) and blood (36.84%). Most case-control studies found an increase in Hg levels in individuals with ASD who were exposed to a polluted environment in the post-natal period. Taken together, the studies suggest that these patients have a deficient detoxification system, and this could worsen the symptoms of the disorder. However, new studies addressing the influence of Hg on the post-natal nervous system and its relationship with ASD should be carried out.

Association of Growth During Infancy with Neurodevelopment and Obesity in Children Born Very Preterm: The Environmental Influences on Child Health Outcomes Cohort.

OBJECTIVE: To evaluate associations between change in weight z score after neonatal intensive care unit (NICU) discharge and neurodevelopmental outcomes and obesity at 12-48 months of age among individuals born very preterm. STUDY DESIGN: This secondary analysis used data from infants born very preterm participating in the Environmental influences on Child Health Outcomes cohort (n = 1400). Growth during infancy was calculated as change in weight z score between NICU discharge and follow-up at a mean of 27 months of age. Very low weight gain was defined as a change in weight z score <-1.67; very high weight gain was a change in weight z score >1.67. Neurodevelopmental outcomes included the Bayley Scales of Infant and Toddler Development, Child Behavior Checklist 1.5-5 years, and Modified Checklist for Autism in Toddlers. Multivariable linear regression was used to estimate associations between increase in weight z score and neurodevelopmental outcomes. RESULTS: Very low weight gain between NICU discharge and follow-up (experienced by 6.4% of participants) was associated with lower scores on cognitive (adjusted mean difference: -4.26; 95% CI: -8.55, -0.04) and language (adjusted mean difference: -4.80; 95% CI: -9.70, -0.11) assessments. Very high weight gain (experienced by 13.6% of participants) was associated with an increased obesity risk (adjusted relative risk: 6.20; 95% CI: 3.99, 9.66) but not with neurodevelopmental outcomes. CONCLUSIONS: Very high weight gain in the first 12-48 months after NICU discharge was associated with a higher risk of obesity at follow-up; very low weight gain was associated with lower scores on cognitive and language assessments.

A de novo variant in RERE causes autistic behavior by disrupting related genes and signaling pathway.

Autism spectrum disorder (ASD) is a highly variable neurodevelopmental disorder that typically manifests childhood, characterized by a triad of symptoms: impaired social interaction, communication difficulties, and restricted interests with repetitive behaviors. De novo variants in related genes can cause ASD. We present the case of a 6-year-old Chinese boy with autistic behavior, including language communication impairments, intellectual disabilities, stunted development, and irritability in social interactions. Using Sanger sequencing, we confirmed a pathogenic in the RERE gene (NM_012102.4) (c.3732delC, p.Tyr1245Thrfs*12; EX21; Het). Subsequently, we generated an RERE point mutation cell line (ReMut) using CRISPR/Cas9 Targeted Genome Editing. Immunofluorescence was conducted to determine the location of the mutant RERE. RNA-sequencing and mass spectrometry analyses were performed to elucidate the ASD-related genes and signaling pathways disrupted by this variant in RERE. We identified 3790 differentially expressed genes and 684 differentially expressed proteins. The SHH signaling pathway was found to be downregulated, and the Hippo pathway was upregulated in ReMut. Genes implicated in autism, such as CNTNAP2, STX1A, FARP2, and GPC1, were significantly downregulated. Simultaneously, we noted alterations in HDAC1 and HDAC2, which are members of the WHHERE complex, suggesting their role in the pathogenesis of this patient. In conclusion, we report a de novo variant in RERE associated with autistic behavior. The finding that ASD is associated with RERE variants underscore the role of genetic factors in ASD and provides insights regarding the mechanisms underlying RERE variants in disease onset.

Autistic Traits Modulate Social Synchronizations Between School-Aged Children: Insights From Three fNIRS Hyperscanning Experiments.

The current study investigated how autistic traits modulate peer interactions using functional near-infrared spectroscopy (fNIRS) hyperscanning. Across three experiments, we tested the effect of copresence, joint activity, and a tangible goal during cooperative interactions on interbrain coherence (IBC) in school-aged children between 9 and 11 years old. Twenty-three dyads of children watched a video alone or together in Experiment 1, engaged in joint or self-paced book reading in Experiment 2, and pretended to play a Jenga game or played for real in Experiment 3. We found that all three formats of social interactions increased IBC in the frontotemporoparietal networks, which have been reported to support social interaction. Further, our results revealed the shared and unique interbrain connections that were predictive of the lower and higher parent-reported autism-spectrum quotient scores, which indicated child autistic traits. Results from a convergence of three experiments provide the first evidence to date that IBC is modulated by child autistic traits.

Age effects on autism heritability and etiological stability of autistic traits.

BACKGROUND: Autism and autistic traits onset in childhood but persist into adulthood. Little is known about how genetic and environmental factors influence autism and autistic traits into adulthood. We aimed to determine age effects on the heritability of clinically diagnosed autism and the etiological stability of autistic traits from childhood to adulthood using twin methods. METHODS: From 23,849 twin pairs in the Swedish Twin Register born between 1959 and 2010, we identified 485 individuals (1.01%, 31.5% female) with a clinical autism diagnosis. We estimated and compared the relative contribution of genetic, shared, and nonshared environmental influences to autism in childhood and adulthood. We further used multivariate twin analysis with four measurement points among 1,348 twin pairs in the longitudinal Twin Study of Child and Adolescent Development to assess the phenotypic and etiological stability of autistic traits - measured with three scales from the Child Behavior Checklist - from childhood to adulthood. RESULTS: Autism heritability was comparable from childhood, (96% [95% CI, 76-99%]) to adulthood (87% [67-96%]). Autistic traits were moderately stable (phenotypic correlation = 0.35-0.61) from childhood to adulthood, and their heritability varied between 52 and 71%. We observed stable as well as newly emerging genetic influences on autistic traits from ages 8-9 to 19-20, and unique nonshared environmental influences at each age. CONCLUSIONS: Genetic factors are important for autism and autistic traits in adulthood and separate genetic studies in adults are warranted.

Emerging drugs for the treatment of irritability associated with autism spectrum disorder.

INTRODUCTION: Autism spectrum disorder (ASD) is an early-onset disorder with a prevalence of 1% among children and reported disability-adjusted life years of 4.31 million. Irritability is a challenging behavior associated with ASD, for which medication development has lagged. More specifically, pharmacotherapy effectiveness may be limited against high adverse effects (considering side effect profiles and patient medication sensitivity); thus, the possible benefits of pharmacological interventions must be balanced against potential adverse events in each patient. AREAS COVERED: After reviewing the neuropathophysiology of ASD-associated irritability, the benefits and tolerability of emerging medications in its treatment based on randomized controlled trials were detailed in light of mechanisms and targets of action. EXPERT OPINION: Succeeding risperidone and aripiprazole, monotherapy with memantine may be beneficial. In addition, N-acetylcysteine, galantamine, sulforaphane, celecoxib, palmitoylethanolamide, pentoxifylline, simvastatin, minocycline, amantadine, pregnenolone, prednisolone, riluzole, propentofylline, pioglitazone, and topiramate, all adjunct to risperidone, and clonidine and methylphenidate outperformed placebo. These effects were through glutamatergic, γ-aminobutyric acidergic, inflammatory, oxidative, cholinergic, dopaminergic, and serotonergic systems. All medications were reported to be safe and tolerable. Considering sample size, follow-up, and effect size, further studies are necessary. Along with drug development, repositioning and combining existing drugs supported by the mechanism of action is recommended.

Early-Life Exposure to 4-Hydroxy-4'-Isopropoxydiphenylsulfone Induces Behavioral Deficits Associated with Autism Spectrum Disorders in Mice.

Exposure to bisphenol A (BPA) during gestation and lactation is considered to be a potential risk factor for autism spectrum disorder (ASD) in both humans and animals. As a novel alternative to BPA, 4-hydroxy-4'-isopropoxydiphenylsulfone (BPSIP) is frequently detected in breast milk and placental barrier systems, suggesting potential transmission from the mother to offspring and increased risk of exposure. Gestation and lactation are critical periods for central nervous system development, which are vulnerable to certain environmental pollutants. Herein, we investigated the behavioral impacts and neurobiological effects of early-life exposure to BPSIP (0.02, 0.1, and 0.5 mg/kg body weight/day) in mice offspring. Behavioral studies indicated that BPSIP exposure induced ASD-like behaviors, including elevated anxiety-related behavior and decreased spatial memory, in both male and female pups. A distinct pattern of reduced social novelty was observed only in female offspring, accompanied by significant alterations in antioxidant levels. Transcriptome analysis demonstrated that differentially expressed genes (DEGs) were mainly enriched in pathways related to behaviors and neurodevelopment, which were consistent with the observed phenotype. Besides, a decrease in the protein levels of complex IV (COX IV) across all tested populations suggests a profound impact on mitochondrial function, potentially leading to abnormal energy metabolism in individuals with autism. Additionally, changes in synaptic proteins, evidenced by alterations in synapsin 1 (SYN1) and postsynaptic density protein-95 (PSD95) levels in the cerebellum and hippocampus, support the notion of synaptic involvement. These findings suggest that BPSIP may induce sex-specific neurotoxic effects that involve oxidative stress, energy generation, and synaptic plasticity.

Resting-state EEG Microstate Features Can Quantitatively Predict Autistic Traits in Typically Developing Individuals.

Autism spectrum disorder (ASD) is not a discrete disorder and that symptoms of ASD (i.e., so-called "autistic traits") are found to varying degrees in the general population. Typically developing individuals with sub-clinical yet high-level autistic traits have similar abnormities both in behavioral performances and cortical activation patterns to individuals diagnosed with ASD. Thus it's crucial to develop objective and efficient tools that could be used in the assessment of autistic traits. Here, we proposed a novel machine learning-based assessment of the autistic traits using EEG microstate features derived from a brief resting-state EEG recording. The results showed that: (1) through the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and correlation analysis, the mean duration of microstate class D, the occurrence rate of microstate class A, the time coverage of microstate class D and the transition rate from microstate class B to D were selected to be crucial microstate features which could be used in autistic traits prediction; (2) in the support vector regression (SVR) model, which was constructed to predict the participants' autistic trait scores using these four microstate features, the out-of-sample predicted autistic trait scores showed a significant and good match with the self-reported scores. These results suggest that the resting-state EEG microstate analysis technique can be used to predict autistic trait to some extent.

Rumination and altered reactivity to sensory input as vulnerability factors for developing post-traumatic stress symptoms among adults with autistic traits.

OBJECTIVE: Recent literature has suggested that individuals with autism spectrum disorder (ASD) or autistic traits (ATs) would be more likely to encounter traumatic events in their lifetime and to develop post-traumatic stress disorder (PTSD). However, the nature of this relationship has not yet been fully elucidated. The aims of this study were to evaluate the relationship between AT and PTSD and to investigate which specific autistic dimension was more associated with trauma and stress-related symptoms. METHODS: A total of 68 subjects with ASD and 64 healthy controls (HCs) were assessed with the Adult Autism Subthreshold Spectrum (AdAS Spectrum) and the Trauma and Loss Spectrum (TALS) questionnaires. Statistical analyses included Mann-Whitney U test, chi-square test, calculation of Spearman's coefficients, and logistic regression analysis. RESULTS: Patients with significant AT reported a 30% rate of PTSD and higher TALS total and domain scores than HCs, among whom no PTSD was found instead. Significant positive correlations were reported between AdAS Spectrum and TALS-SR scores in the whole sample. AdAS Spectrum total scores were statistically predictive of the presence of PTSD. High scores at AdAS Spectrum Inflexibility and adherence to routine and Restrictive interest and rumination domains were identified as positive predictors of a probable PTSD. CONCLUSION: Compared to HCs, subjects with significant AT are more likely to present symptoms of PTSD. In particular, AT related to ruminative thinking, narrow interests, and sensorial reactivity would seem to predict the presence of post-traumatic stress symptomatology.

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

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

Neural underpinnings of processing combinatorial unstated meaning and the influence of individual cognitive style.

We investigated the neurocognitive mechanisms underlying the processing of combinatorial unstated meaning. Sentences like "Charles jumped for 5 minutes." engender an iterative meaning that is not explicitly stated but enriched by comprehenders beyond simple composition. Comprehending unstated meaning involves meaning contextualization-integrative meaning search in sentential-discourse context. Meanwhile, people differ in how they process information with varying context sensitivity. We hypothesized that unstated meaning processing would vary with individual socio-cognitive propensity indexed by the Autism-Spectrum Quotient (AQ), accompanied by differential cortical engagements. Using functional magnetic resonance imaging, we examined the processing of sentences with unstated iterative meaning in typically-developed individuals and found an engagement of the fronto-parietal network, including the left pars triangularis (L.PT), right intraparietal (R.IPS), and parieto-occipital sulcus (R.POS). We suggest that the L.PT subserves a contextual meaning search, while the R.IPS/POS supports enriching unstated iteration in consideration of event durations and interval lengths. Moreover, the activation level of these regions negatively correlated with AQ. Higher AQ ties to lower L.PT activation, likely reflecting weaker context sensitivity, along with lower IPS activation, likely reflecting weaker computation of events' numerical-temporal specifications. These suggest that the L.PT and R.IPS/POS support the processing of combinatorial unstated meaning, with the activation level modulated by individual cognitive styles.

Mental Health Evaluation of Younger and Older Adolescents Referred to the Center of Expertise on Gender Dysphoria in Amsterdam, The Netherlands.

The present study aimed to investigate whether differences exist between younger and older presenting adolescents at the Center of Expertise on Gender Dysphoria regarding psychological functioning and autistic traits. A total of 1487 consecutively assessed adolescents between 2000 and 2018 were divided in younger presenters (age ≤ 13.9 years) and older presenters (age ≥ 14 years). Of younger presenters, 227 (41.1%) were assigned male at birth and 325 (58.9%) assigned female at birth. In older presenters, 279 (29.8%) were assigned male at birth and 656 (70.2%) assigned female at birth. Behavioral and emotional problems were assessed with the Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR). For autism traits, the Social Responsiveness Scale (SRS) was used. Compared to younger presenters, on both the CBCL and YSR older presenters had higher Total Problem (ß = 1.75, p = .005, CI 0.53-2.97, R2 = .04 and ß = 4.20, p < .001, CI 2.99-5.40, R2 = .07, respectively) and Internalizing Problem (ß = 4.43, p < .001, CI 3.13-5.74, R2 = .06 and ß = 6.69, p < .001, CI 5.31-8.07, R2 = .12, respectively) scores. Regarding autistic traits, a higher mean SRS total score was found in older presenting assigned males at birth (ß = 4.55, p = .036, CI 0.30-8.81, R2 = .34). In assigned females at birth, no statistically significant difference between older and younger presenters was found in mean SRS total score (ß = 1.19, p = .063, CI - 0.07 to 2.45, R2 = .39). Differences in mental health exist between younger and older presenting adolescents and call for an individualized approach in the clinical care of transgender adolescents.

Folic acid and autism: updated evidences.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that impairs communication, socialization, and behavior. The association of ASD with folic acid has been investigated due to the importance of this vitamin for neurological health. This study is an update of the publication 'Folic acid and autism: What do we know?' and aims to systematically review studies examining the relationship between folic acid and ASD. The search resulted in 2,389 studies on folic acid and ASD, which were selected by two reviewers based on their titles and abstracts. Studies meeting the inclusion criteria were fully read. The 52 included studies involved 10,429 individuals diagnosed with ASD and assessed the intake of vitamin B6, folic acid, and vitamin B12; serum levels of these vitamins, homocysteine, and methionine; therapeutic interventions using folic acid; and the association between maternal exposure to this vitamin and the risk of ASD. The evidence of insufficient folic acid intake in most individuals with ASD remains consistent in this update. No association was found between maternal exposure to folic acid and the risk of ASD in their children. Despite observed improvements in communication, socialization, and behavior in individuals with ASD following folic acid interventions, it is crucial to consider the individuality and complexity of ASD. Given the relevance of the topic, there remains a need for more high-quality research and clinical trials characterized by rigorous methodological designs.

The impact of spectral basis set composition on estimated levels of cingulate glutamate and its associations with different personality traits.

BACKGROUND: 1H-MRS is increasingly used in basic and clinical research to explain brain function and alterations respectively. In psychosis research it is now one of the main tools to investigate imbalances in the glutamatergic system. Interestingly, however, the findings are extremely variable even within patients of similar disease states. One reason may be the variability in analysis strategies, despite suggestions for standardization. Therefore, our study aimed to investigate the extent to which the basis set configuration- which metabolites are included in the basis set used for analysis- would affect the spectral fit and estimated glutamate (Glu) concentrations in the anterior cingulate cortex (ACC), and whether any changes in levels of glutamate would be associated with psychotic-like experiences and autistic traits. METHODS: To ensure comparability, we utilized five different exemplar basis sets, used in research, and two different analysis tools, r-based spant applying the ABfit method and Osprey using the LCModel. RESULTS: Our findings revealed that the types of metabolites included in the basis set significantly affected the glutamate concentration. We observed that three basis sets led to more consistent results across different concentration types (i.e., absolute Glu in mol/kg, Glx (glutamate + glutamine), Glu/tCr), spectral fit and quality measurements. Interestingly, all three basis sets included phosphocreatine. Importantly, our findings also revealed that glutamate levels were differently associated with both schizotypal and autistic traits depending on basis set configuration and analysis tool, with the same three basis sets showing more consistent results. CONCLUSIONS: Our study highlights that scientific results may be significantly altered depending on the choices of metabolites included in the basis set, and with that emphasizes the importance of carefully selecting the configuration of the basis set to ensure accurate and consistent results, when using MR spectroscopy. Overall, our study points out the need for standardized analysis pipelines and reporting.

Correlation between autistic traits and brain functional connectivity in preschoolers with autism spectrum disorder: a resting state MEG study.

BACKGROUND: Neurophysiological studies recognized that Autism Spectrum Disorder (ASD) is associated with altered patterns of over- and under-connectivity. However, little is known about network organization in children with ASD in the early phases of development and its correlation with the severity of core autistic features. METHODS: The present study aimed at investigating the association between brain connectivity derived from MEG signals and severity of ASD traits measured with different diagnostic clinical scales, in a sample of 16 children with ASD aged 2 to 6 years. RESULTS: A significant correlation emerged between connectivity strength in cortical brain areas implicated in several resting state networks (Default mode, Central executive, Salience, Visual and Sensorimotor) and the severity of communication anomalies, social interaction problems, social affect problems, and repetitive behaviors. Seed analysis revealed that this pattern of correlation was mainly caused by global rather than local effects. CONCLUSIONS: The present evidence suggests that altered connectivity strength in several resting state networks is related to clinical features and may contribute to neurofunctional correlates of ASD. Future studies implementing the same method on a wider and stratified sample may further support functional connectivity as a possible biomarker of the condition.

Autistic traits and ARFID-associated eating behaviors in preschoolers: Mediating effects of sensory processing patterns.

OBJECTIVE: This study aimed to examine the association between autistic traits and Avoidant Restrictive Food Intake Disorder (ARFID)-associated eating behaviors in preschool-age children and investigated whether this association was mediated by sensory processing patterns. METHOD: A cross-sectional, parent-reported study was conducted between July 2022 and March 2023 among 503 preschoolers aged 4-6 years in China. Parents provided assessments of their children's autistic traits using the Social Responsiveness Scale, sensory processing patterns using the Short Sensory Profile 2, and ARFID-associated eating behaviors using the Nine Items ARFID Screen. The mediation model based on ordinary least squares regression was employed to test the mediating effects of sensory processing patterns between autistic traits and ARFID-associated eating behaviors. RESULTS: The results indicated significant associations among autistic traits, ARFID-associated eating behaviors, and sensory processing patterns. Moreover, mediation analyses revealed that sensory processing patterns played a partial mediating role in the relationship between autistic traits and ARFID-associated eating behaviors. Specifically, autistic traits were observed to weaken ARFID-associated eating behaviors, particularly picky eating and poor appetite, through Registration, while simultaneously fostering them through Sensitivity and Avoiding. DISCUSSION: Our study is limited to some extent by the inability to draw longitudinal conclusions from cross-sectional data. Nevertheless, it underscores the significance of early identification and intervention for food avoidance/restriction behaviors due to sensory processing abnormalities in children with heightened autistic traits. This proactive approach may contribute to mitigating ARFID-associated eating behaviors that might drive clinical symptoms of ARFID.