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Initial indications propose that repetitive transcranial magnetic stimulation (rTMS) could mitigate clinical manifestations in patients with autism spectrum disorder (ASD). Nevertheless, the precise mechanisms responsible for these therapeutic and behavioral outcomes remain elusive. We examined alterations in effective connectivity induced by rTMS using concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) in children with ASD. TMS-EEG data were acquired from 12 children diagnosed with ASD both before and following rTMS treatment. The rTMS intervention regimen included delivering 5-s trains at a frequency of 15 Hz, with 10-min intervals between trains, targeting the left parietal lobe. This was conducted on each consecutive weekday over 3 weeks, totaling 15 sessions. The dynamic EEG network analysis revealed that following the rTMS intervention, long-range feedback connections within the brains of ASD patients were strengthened (e.g., frontal to parietal regions, frontal to occipital regions, and frontal to posterior temporal regions), and short-range connections were weakened (e.g., between the bilateral occipital regions, and between the occipital and posterior temporal regions). In alignment with alterations in network connectivity, there was a corresponding amelioration in fundamental ASD symptoms, as assessed through clinical scales post-treatment. According to our findings, people with ASD may have increased long-range frontal-posterior feedback connection on application of rTMS to the parietal lobe.

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Eating problems, such as food selectivity or picky eating, are thought to be an epiphenomenon of autism spectrum disorders (ASD). Yet eating problems are also common in the general pediatric population and overlap with ASD symptoms. However, the temporal association between ASD symptoms and eating problems is poorly understood. This study examines the bidirectional association between ASD symptoms and eating problems across child development, and investigates whether these associations differ by child sex. Participants (N = 4,930) were from the population-based Generation R Study. Parents reported their child's ASD symptoms and eating problems using the Child Behavior Checklist at 5 assessments from toddlerhood to adolescence (1.5 to 14 years, 50% girls). A Random Intercept Cross-Lagged Panel Model was used to examine the lagged associations between ASD symptoms and eating problems at the within-person level, controlling for stable, trait-like differences at the between-person level. At the between-person level, there was a strong correlation between ASD symptoms and eating problems (ß = .48, 95% CI: 0.38 to 0.57). Controlling for these between-person effects, there was limited evidence for consistent, predictive effects of ASD symptoms and eating problems at the within-person level. Associations did not differ by child sex. Findings suggest that ASD symptoms and eating problems may represent a cluster of traits that are highly stable from early childhood to adolescence, which have a minimal reciprocal effect at the individual-level. Future research could focus on these trait-like qualities to inform the development of supportive, family-focused interventions.

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Autism spectrum disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder characterized by stereotyped behaviors, specific interests, and impaired social and communication skills. Synapses are fundamental structures for transmitting information between neurons. It has been reported that synaptic deficits, such as the increased or decreased density of synapses, may contribute to the onset of ASD, which affects the synaptic function and neuronal circuits. Therefore, targeting the recovery of the synaptic normal structure and function may be a promising therapeutic strategy to alleviate ASD symptoms. Exercise intervention has been shown to regulate the structural plasticity of synapses and improve ASD symptoms, but the underlying molecular mechanisms require further exploration. In this review, we highlight the characteristics of synaptic structural alterations in the context of ASD and the beneficial effects of an exercise intervention on improving ASD symptoms. Finally, we explore the possible molecular mechanisms of improving ASD symptoms through exercise intervention from the perspective of regulating synaptic structural plasticity, which contributes to further optimizing the related strategies of exercise intervention promoting ASD rehabilitation in future.

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Repetitive transcranial magnetic stimulation (rTMS) is growingly applied in autism spectrum disorder (ASD) due to its potential therapeutic value, however, its effects on functional network configuration and the mechanism underlying clinical improvement are still unclear. In this study, we examined the alternations of functional connectivity induced by rTMS using resting-state electroencephalogram (EEG) in children with ASD. Resting-state EEG was obtained from 24 children with ASD before and after rTMS intervention and from 24 age- and gender-matched typically developing (TD) children. The rTMS intervention course consisted of five 5-s trains at 15 Hz, with 10-min inter-train intervals, on the left parietal lobe each consecutive weekday for 3 weeks (15 sessions in total). Children with ASD showed significantly hypo-connected networks and sub-optimal network properties at both global and local levels, compared with TD peers. After rTMS intervention, long-range intra- and inter-hemispheric connections were significantly promoted, especially those within the alpha band. Meanwhile, network properties at both local and global levels were greatly promoted in the delta, theta, and alpha bands. Consistent with the changes in the network connectivities and properties, the core symptoms in ASD were also relieved measured by clinical scales after treatment. The findings of this study demonstrate that high-frequency rTMS over the parietal lobe is potentially an effective strategy to improve core symptoms by enhancing long-range connectivity reorganization in ASD.

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Autism spectrum disorder (ASD) is a developmental disorder of variable severity, characterized by difficulties in social interaction, communication, and restricted or repetitive patterns of thought and behavior. In 2018, the incidence of ASD was 2.4 times higher than estimated in 2000. Behavior and brain development abnormalities are present in the complex disorder of ASD. Nutritional status plays a key role in the incidence and severity of the core symptoms of ASD. The aim of this study was to review the available peer-reviewed studies that evaluated the relationship between amino acids, choline, B vitamins, and ASD incidence and/or severity of symptoms. Through examining plasma profiles, urine samples, and dietary intake, researchers found that low choline, abnormal amino acid, and low B vitamin levels were present in children with ASD compared to those without ASD. The evidence supports the need for future research that implements simultaneous supplementation of all essential nutrients in individuals with ASD and among prenatal mothers. Future evidence could lead to scientific breakthroughs, ultimately reducing the rates of ASD incidence and severity of symptoms by applying nutritional interventions in at-risk populations.

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Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders. The etiology of autism remains unclear, but a growing body of evidence indicates that phthalates play a role in its pathogenesis. The aim of this study was to compare the urine levels of phthalates in children with ASD and healthy children. We also explored whether phthalates have an effect on ASD symptoms. The participants in this study included 101 children with ASD (79 boys and 22 girls) and 101 sex- and age-matched controls. The levels of phthalates were analyzed by gas chromatography-mass spectrometry (GC-MS). We detected significant differences in monoethyl phthalate (MEP) levels between the severe ASD and control groups (p < 0.05). Mono-n-butyl phthalate (MBP) concentration was positively correlated with language skill impairment in ASD (ß: 0.387, p = 0.041). MEP levels were associated with the CARS "Imitation" score in all children (OR: 1.470). MBP levels were associated with the "Nonverbal Communication" score among boys (OR: 1.233), and MEP levels were associated with the "Nonverbal Communication" score among girls (OR: 2.648). MEP levels were related to the CARS total score after adjustment for sex (ß: 1.524, p = 0.047). Compared with the reference mono(2-ethylhexyl) phthalate (MEHP) group, children with ASD in the medium-exposure group had an OR of 3.370 for aggravating ASD severity. These results suggested that increased exposure to phthalates contributes to more ASD symptoms and that there are potentially sex-specific associations. These findings warrant further confirmation.

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BACKGROUND: There is substantial variability in adaptive skills among individuals with Down syndrome. Few studies, however, have focused on the early developmental period or on the potential sources of variability in adaptive skills. This study characterizes adaptive skills in young children with Down syndrome and investigates child characteristics associated with adaptive skills. METHODS: Participants were 44 children with Down syndrome ranging in age from 2.50 to 7.99 years (M = 4.66 years, SD = 1.46). The Vineland Adaptive Behavior Scales-3 (VABS-3) Comprehensive Interview Form was used to assess adaptive behavior in the three core domains: socialization, daily living, and communication skills. Caregivers also reported on motor skills and autism spectrum disorder symptoms. Child cognitive abilities were assessed. RESULTS: Analyses comparing mean standard score performance across the three VABS-3 core domains demonstrated significant differences between all pairs of domains, resulting in a group-level pattern of socialization > daily living > communication skills. At the individual level, 10 different patterns of relative strength and weakness were identified, with only 18% of participants evidencing significant differences between adaptive skill domain standard scores corresponding to the group-level pattern of significant differences. Child characteristics (cognitive abilities, motor skills, and autism spectrum disorder symptoms) were significantly associated with VABS-3 adaptive domain standard scores. CONCLUSION: These findings underscore the importance of individualizing intervention programs focused on improving the adaptive skills of young children with Down syndrome based on consideration of the child's relative adaptive strengths and weaknesses.

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This study assessed the potential short-term effects of COVID-19 stay-at-home restrictions on ratings of ASD and comorbid symptoms severity and adaptive functioning of 69 youth, ages 8-16 years with ASD without intellectual disability. Parent/caregiver ratings were being collected in fall and spring over approximately two years when the restrictions were imposed four months prior to the final data collection point. Results indicated no significant changes in parent/caregiver ratings of ASD symptom severity, comorbid symptoms severity, social skills, or adaptive behaviors following the stay-at-home restrictions and little variability across the four data collection points. Although findings suggested minimal short-term effects on these symptoms and adaptive skills, ongoing monitoring is needed to assess longer-term impacts.

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Background: The presence of mild traumatic brain injury (mTBI) increases post-traumatic stress disorder (PTSD) symptoms in the months following injury. However, factors that link mTBI and PTSD development are still unclear. Acute stress responses after trauma have been associated with PTSD development. mTBI may impair cognitive functions and increase anxiety immediately after trauma. Objective: This research aimed to test the possibility that mTBI increases acute stress symptoms rapidly, which in turn results in PTSD development in the subsequent months. Method: Fifty-nine patients were recruited from the emergency rooms of local hospitals. Post-mTBI, acute stress, and PTSD symptom severity were measured using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Acute Stress Disorder Scale (ASDS), and PTSD Checklist for DSM-5 (PCL-5), respectively. Results: Moderated mediation analysis indicated that ASDS, at 2 weeks post-trauma, mediated the relationship between RPQ scores at 2 weeks and PCL-5 scores at 3 months post-trauma, only for patients who met mTBI diagnostic criteria. Conclusions: These findings present preliminary evidence suggesting that acute stress disorder symptoms may be one of the mechanisms involved in the development of PTSD among trauma survivors who have experienced mTBI, which provides a theoretical basis for early intervention of PTSD prevention after mTBI.

Antecedentes: La presencia de lesiones cerebrales traumáticas leves (mTBI, por su sigla en inglés) aumenta los síntomas del trastorno de estrés postraumático (TEPT) en los meses posteriores al daño. Sin embargo, los factores que relacionan mTBI y el desarrollo del TEPT no están claros aún. Es posible que mTBI induzca una respuesta aguda al estrés inmediatamente después del trauma, que a su vez, se asocie al desarrollo posterior de TEPT.Objetivo: Este estudio buscó probar la hipótesis de si la asociación de mediación entre mTBI, estrés agudo y severidad de los síntomas de TEPT depende del estado de mTBI.Métodos: Se reclutó a cincuenta y nueve pacientes de las salas de emergencia de hospitales locales. Se midió la severidad de los síntomas post-mTBI y de estrés agudo dentro de las 2 semanas posteriores al trauma utilizando el cuestionario de síntomas post-concusión de Rivermead (RPQ, por su sigla en inglés) y la Escala para el Trastorno de Estrés Agudo (ASDS, por su sigla en inglés), respectivamente. Se midió la severidad de los síntomas de TEPT 3 meses después del trauma utilizando la Lista de Chequeo para TEPT del DSM-5 (PCL-5, por su sigla en inglés).Resultados: Los análisis de mediación moderada indicaron que los puntajes de ASDS, a las 2 semanas post-trauma, mediaban la relación entre los puntajes de RPQ a las 2 semanas y los puntajes de la PCL-5 a los 3 meses post-trauma, sólo para pacientes que cumplían los criterios diagnósticos para mTBI.Conclusiones: Estos hallazgos presentan evidencia preliminar que sugiere que los síntomas del trastorno de estrés agudo pueden ser uno de los mecanismos involucrados en el desarrollo del TEPT entre los sobrevivientes de trauma con un diagnóstico de mTBI, lo cual provee una base teórica para la intervención temprana de TEPT después de mTBI.

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Even genetic disorders associated with monogenic aetiologies are characterized by complex and variable risk for poor outcomes, highlighting the need to follow trajectories longitudinally. Here, we investigated the longitudinal relationships between attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) symptoms in a population at high risk for both: boys with fragile X syndrome. 59 boys with fragile X syndrome aged 3-10 years old at entry participated in this study, and were followed up one and two years after their first visit. As expected, we found strong relationships over three timepoints for ADHD symptoms (as measured by the parent-rated Conners scale) and ASD symptoms (as measured by the Social Communication Questionnaire [SCQ]). In addition, using structural equation modeling (SEM) we found that ADHD symptoms at time 2 predicted ASD symptoms at time 3, suggestive of a causal relationship. Importantly, these relationships hold when including chronological age at entry to the study, as well as when including severity of impairment as measured by IQ, and their effects on both ASD and ADHD symptoms do not reach significance. This result highlights the need to study outcomes longitudinally and it informs the comorbidity of the two symptom domains in FXS as well as their potential directionality, both of which have been little researched. In addition, our findings may suggest a future need to study how ADHD symptoms and their treatment impact individuals with ASD.

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OBJECTIVE: To measure the knowledge of healthcare professionals about increasingly prevalent Autism Spectrum Disorder (ASD) along with perceptions around its management and prognosis and comparison across various specialties. METHODS: This Cross sectional survey based comparative analysis took place at Maternity and Children Hospital and King Faisal Hospital Makkah from December 2017 to May 2018. The validated self-administered "Knowledge about childhood autism among health workers" questionnaire was used along with additional questions regarding perceptions about ASD. The mean and mean percent scores were calculated. Chi squared test and ANOVA were applied to find the association between quantitative and qualitative variables respectively. RESULTS: Out of 162 participants, 153 returned the questionnaire and 147 were included in final analysis. Physicians constituted 81.6% (120) of participants. The mean score for participants was 9.80(S.E.M ±0.32) where non-physicians yielded higher mean score (11.2±4.41) as compared to physicians (9.6±3.28) (p=0.113). Psychiatrists had highest score of 16/19 while general physicians had lowest (6/19). Participants with more years of experience had higher mean scores (p-value = 0.01). About 72.10% (106) of participants opted for medication as a treatment option. Nearly 38.1% (56) of participants were skeptical about improvement of ASD with early interventions. CONCLUSION: There is a lack of knowledge about ASD amongst healthcare professionals in Saudi Arabia. Experienced professionals working with ASD children can be utilized to deliver targeted trainings nationwide.

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Based on limitations in previous research evidence, we concluded that more research is needed for deeper understanding of how social-emotional and behavioral (SEB) outcomes among infant-toddler-aged children in the general population are associated with early motor development. In this study, we investigated associations between early competencies and problems, as measured by the Brief Infant-Toddler Social and Emotional Assessment (BITSEA), and the timing of achievement of the main gross and fine motor milestones usually attained during the first year of life in a general population context. The study sample consisted of 515 infants (mean age 12.9 [SD 0.9] months) and their parents (514 mothers, 434 fathers), who were recruited in child health centers in Northern Finland. The infants were divided into two groups, based on their BITSEA screen status, and motor milestone achievement ages were compared across BITSEA screen status No Concern and Of-Concern infants. An Of-Concern screen status on the maternal and paternal Competence scale and Autism spectrum disorder (ASD) item cluster was associated with later infant achievement ages for gross motor milestones. By contrast, infants who were screened to be in the Of-Concern range on the maternal Problem scale achieved gross motor milestones earlier than infants with the corresponding No Concern screen status. No significant associations were found between the paternal Problem scale screen status and infant motor development. In further analyses, the strongest associations were found between an Of-Concern screen status on the paternal Competence scale and ASD item cluster and infant motor development. The findings indicate that the inclusion of infant motor developmental information may assist early identification and the clinical interpretation of parental reports of early SEB problems. Clinical implications of the current findings are discussed in the paper.

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This study examined additive and interactive effects of callous unemotional (CU) traits and autism spectrum disorders (ASD) symptoms in relation to trait empathy, in boys with oppositional defiant disorder (ODD) or conduct disorder (CD). Participants were 49 boys with ODD/CD, aged between 7-12 years. Boys completed a questionnaire measure of empathic sadness and a broader questionnaire measure of affective and cognitive empathy. Parents and teachers reported on CU traits, and parents reported on ASD symptoms. In agreement with predictions, results reveal a negative association between CU traits and empathic sadness, particularly strong for ODD/CD boys with low levels of ASD symptoms. Results also reveal a negative association between ASD symptoms and cognitive empathy. Findings suggest that CU traits and ASD symptoms are associated with distinct empathy deficits with poor empathic sadness being more typical of CU traits than ASD symptoms.

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Recent studies support several overlapping traits between autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD), assuming the existence of a combined phenotype. The aim of our study was to evaluate the common or distinctive clinical features between ASD and ADHD in order to identify possible different phenotypes that could have a clinical value. We enrolled 181 subjects divided into four diagnostic groups: ADHD group, ASD group, ASD+ADHD group (that met diagnostic criteria for both ASD and ADHD), and control group. Intelligent quotient (IQ), emotional and behavior problems, ADHD symptoms, ASD symptoms, and adaptive behaviors were investigated through the following test: Wechsler Intelligence Scale for Children, Wechsler Preschool and Primary Scale of Intelligence or Leiter International Performances Scale Revised, Child Behavior Checklist, Conners' Rating Scales-Revised, SNAP-IV Rating Scale, the Social Communication Questionnaire, Vineland Adaptive Behavior Scales. The ASD+ADHD group differs from ADHD or ASD in some domains such as lower IQ mean level and a higher autistic symptoms severity. However, the ASD+ADHD group shares inattention and hyperactivity deficit and some emotional and behavior problems with the ADHD group, while it shares adaptive behavior impairment with ASD group. These findings provide a new understanding of clinical manifestation of ASD+ADHD phenotype, they may also inform a novel treatment target.

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