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Individuals diagnosed with autism spectrum disorder (ASD) are more likely to have suicidal thoughts and behaviors. However, little research delineates the temporal and mechanistic associations between potential risk factors and suicidality in autistic individuals. We assessed 129 autistic and 121 age-matched and sex-assigned-at-birth-matched typically developing (TD) children and youth at baseline and follow-up. We evaluated internalizing/externalizing problems, bullying experiences, and three executive function tasks at a mean baseline age of 13.4 years (standard deviation: 4.2 years). After an average of 5.8 years (standard deviation: 1.7 years), we evaluated their suicidal thoughts and behaviors. The experiences of being bullied partially mediated the temporal relationship between pre-existing ASD and later-reported suicidal thoughts. Several cognitive flexibility and sustained attention indices mediated the temporal relationship between pre-existing ASD and later-reported suicidal thoughts. A multiple mediation model confirmed that bullying victimization and cognitive flexibility jointly mediated the temporal relationship between ASD and suicidal thoughts. Better cognitive flexibility and experiences of bullying victimization in autistic children/youth were both associated with higher risks of later-reported suicidal thoughts in adolescence/adulthood. School bullying-prevention programs and tailored clinical support for autistic youth with better cognitive flexibility are warranted for personalized suicide prevention for the autistic population. Autistic people are more likely to experience suicidal thoughts and behaviors. The underlying relationships between potential risk factors and suicidal thoughts and behaviors in autistic individuals remain unclear. To understand this, we investigated whether specific factors in childhood/youth explain the effects of pre-existing autism spectrum disorder (ASD) diagnoses on later suicidal thoughts and behaviors in adolescence/adulthood. We assessed internalizing and externalizing problems, bullying experiences, and executive functions (including cognitive flexibility, sustained attention, and spatial working memory) at an average baseline age of 13.4 years and suicidal thoughts and behaviors at an average follow-up age of 19.2 years among 129 autistic and 121 typically developing (TD) individuals. During the follow-up period in adolescence/adulthood, autistic individuals were more likely to report suicidal thoughts than TD individuals. Being bullied partially accounted for the relationship between a pre-existing ASD diagnosis and later-reported higher suicidal thoughts. Contrary to our hypothesis, higher (instead of lower) cognitive flexibility in some autistic young people appeared to partially explain their higher rates of suicidal thoughts compared with typically developing young people. The findings imply that school bullying prevention and tailored intervention programs for autistic people, especially those with higher cognitive flexibility, are warranted to reduce their risks of experiencing suicidal thoughts. [ABSTRACT FROM AUTHOR]

Individuals with autism spectrum disorder (ASD) often experience lifelong social communication challenges and are more vulnerable to school bullying. Addressing their social difficulties and school bullying requires evidence‐based interventions. PEERS® (Program for the Education and Enrichment of Relational Skills) was adapted and translated for Taiwanese adolescents. This randomized controlled study aimed to examine the effectiveness of the Taiwanese version of PEERS® in reducing school bullying and enhancing social function among autistic adolescents. Twenty‐one autistic adolescents (mean age 14.29 ± 1.67 years; female n = 733.33%) were randomized to a treatment group (TG, n = 10) or a delayed treatment control group (DTG, n = 11). The outcome measures (school bullying, social challenges, social skills knowledge, and social skills performance) were assessed at baseline, post‐treatment, and follow‐up. The group and time interaction analyses revealed greater magnitudes of reduction in general school bullying (p < 0.001), victimization (p < 0.001), perpetration (p = 0.012), social challenges (p = 0.001), and peer conflicts (p < 0.001), and improvement in social knowledge (p < 0.001) in the TG group than the DTG group. The findings suggest that the PEERS® program tailored for Taiwanese adolescents is effective in reducing school bullying, decreasing social challenges, and enhancing social skills among autistic adolescents, with very large effect sizes (Cohen's d ranging from 1.19 to 2.88). Consequently, participation in the PEERS® program is recommended for adolescents with social difficulties to improve their social communication and interactions to offset school bullying and other social challenges related to adverse outcomes. Lay Summary: This study examined the effectiveness of the PEERS® program, adapted for Taiwanese autistic teenagers. The findings suggest that the program effectively improves social function and reduces the risk of bullying in school for these teens. Teenagers with social difficulties, especially those on the autism spectrum, should be encouraged to participate in the PEERS® program, which provides essential skills and strategies to cope with social difficulties and school bullying. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneous and complex genetic underpinnings. Our previous microarray gene expression profiling identified significantly different neuregulin-2 gene (NRG2) expression between ASD patients and controls. Thus, we aimed to clarify whether NRG2 is a candidate gene associated with ASD. The study consisted of two stages. First, we used real-time quantitative PCR in 20 ASDs and 20 controls to confirm the microarray gene expression profiling results. The average NRG2 gene expression level in patients with ASD (3.23 ± 2.80) was significantly lower than that in the controls (9.27 ± 4.78, p < 0.001). Next, we conducted resequencing of all the exons of NRG2 in a sample of 349 individuals with ASD, aiming to identify variants of the NRG2 associated with ASD. We identified three variants, including two single nucleotide variants (SNVs), IVS3 + 13A > G (rs889022) and IVS10 + 32T > A (rs182642591), and one small deletion at exon 11 of NRG2 (delGCCCGG, rs933769137). Using data from the Taiwan Biobank as the controls, we found no significant differences in allele frequencies of rs889022 and rs182642591 between two groups. However, there is a significant difference in the genotype and allele frequency distribution of rs933769137 between ASDs and controls (p < 0.0001). The small deletion is located in the EGF-like domain at the C-terminal of the NRG2 precursor protein. Our findings suggest that NRG2 might be a susceptibility gene for ASD. [ABSTRACT FROM AUTHOR]

The mediators of real-world executive functions in autism during the transition into adulthood are mainly unknown. This study aimed to identify the mediators for the behavioral and cognitive domains of real-world executive functions in late adolescent and young adult autistic populations. We followed up 289 autistic children (aged 11.6 ± 3.8, male 82.2%) and 203 non-autistic controls (10.7 ± 2.9, 66.5%) to their ages of 16.9 ± 4.7 and 15.8 ± 3.9, respectively. The Behavior Rating Inventory of Executive Function, comprising two global scales (Behavioral Regulation Index and the Metacognitive Index), was used to assess real-world executive functions at Time 2. Mediators of behavior regulation and metacognition were explored among a wide range of clinical correlates and parental bonding. We found that the autistic group had lower executive functions than the non-autistic group with lower behavior regulation and metacognition subscores. Several childhood factors were significant mediators. Multiple mediation analyses revealed that childhood inattention remained a significant mediator for both behavior regulation and metacognition in late adolescence, and peer problems were the specific mediators of metacognition. Our findings suggest several childhood factors may mediate real-world executive functions during late adolescence. Treating common mediators such as inattention may improve real-world executive functions in autistic individuals during adulthood. Childhood factors that predict real-world executive function in autism spectrum disorder during the transition into adulthood are largely unknown. This study aimed to identify the predictors for the behavioral and cognitive aspects of real-world executive function in late adolescent and young adult autistic populations. We followed up 289 autistic youth (mean age 11.6 years) and 203 non-autistic controls (10.7 years) to their ages of 16.9 and 15.8, respectively. The Behavior Rating Inventory of Executive Function scale was used to measure the real-world executive function at late adolescence and young adulthood at follow-up. Potential predictors such as autistic symptoms, inattention or hyperactivity symptoms, peer relationship, emotional symptoms, and parenting styles were assessed in childhood at first enrollment. The results showed that childhood inattention, withdrawn behaviors, social communication difficulties, and child-reported emotion and inattention/hyperactivity may predict real-world lower executive function in late adolescence and young adults with autism. When separating executive function into behavioral and cognitive aspects, we found that oppositional behaviors and peer problems were specific predictors for behavioral regulation and cognitive function, respectively. Our findings suggested that treating common predictors in childhood, such as inattention, may potentially improve real-world executive function in autism during the transition into adulthood. [ABSTRACT FROM AUTHOR]

Background: The right inferior frontal gyrus (RIFG) is a potential beneficial brain stimulation target for autism. This randomized, double-blind, two-arm, parallel-group, sham-controlled clinical trial assessed the efficacy of intermittent theta burst stimulation (iTBS) over the RIFG in reducing autistic symptoms (NCT04987749)., Methods: Conducted at a single medical center, the trial enrolled 60 intellectually able autistic individuals (aged 8-30 years; 30 active iTBS). The intervention comprised 16 sessions (two stimulations per week for eight weeks) of neuro-navigated iTBS or sham over the RIFG. Fifty-seven participants (28 active) completed the intervention and assessments at Week 8 (the primary endpoint) and follow-up at Week 12., Results: Autistic symptoms (primary outcome) based on the Social Responsiveness Scale decreased in both groups (significant time effect), but there was no significant difference between groups (null time-by-treatment interaction). Likewise, there was no significant between-group difference in changes in repetitive behaviors and exploratory outcomes of adaptive function and emotion dysregulation. Changes in social cognition (secondary outcome) differed between groups in feeling scores on the Frith-Happe Animations (Week 8, p = 0.026; Week 12, p = 0.025). Post-hoc analysis showed that the active group improved better on this social cognition than the sham group. Dropout rates did not vary between groups; the most common adverse event in both groups was local pain. Notably, our findings would not survive stringent multiple comparison corrections., Conclusions: Our findings suggest that iTBS over the RIFG is not different from sham in reducing autistic symptoms and emotion dysregulation. Nonetheless, RIFG iTBS may improve social cognition of mentalizing others' feelings in autistic individuals.

Background: There have been concerns about the potential cardiovascular (CV) adverse effects associated with methylphenidate (MTH) use. However, only limited evidence exists on the long-term safety of MTH., Objective: To evaluate whether MTH use is associated with long-term CV risk., Methods: This was a retrospective cohort study using 2003-2017 data from the Health and Welfare Database in Taiwan. Patients newly diagnosed with attention deficit and hyperactivity disorder (ADHD) and between 3 and 18 years of age were included. Two treatment statuses were assessed: initial treatment ≥7 days and ≥180 days. Patients treated with MTH were compared with those receiving non-medication therapy. One-to-one propensity score matching was used to balance between-group differences. Study outcomes included major CV events, chronic CV disease, cardiogenic shock and all-cause mortality. Cox proportional hazard models were used to estimate HRs between the two groups., Results: We began with 307 459 patients with ADHD. After exclusion, 224 732 patients were included in the final cohort. The results showed that compared with non-ADHD medication users, patients who were treated with MTH for more than 7 days had a similar risk of major CV events (HR 0.85, 95% CI 0.72 to 0.99; p=0.040). Identical trends were found in groups who were treated for more than 180 days (HR 0.83, 95% CI 0.69 to 1.00; p=0.050). The results of the sensitivity analyses were consistent with the main analyses across all groups and individual outcomes., Conclusion: Short-term MTH use did not increase CV risk among patients with ADHD. More evidence on long-term MTH use and risk of cardiogenic shock and death is warranted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Lay Abstract: Autistic people are more likely to experience suicidal thoughts and behaviors. The underlying relationships between potential risk factors and suicidal thoughts and behaviors in autistic individuals remain unclear. To understand this, we investigated whether specific factors in childhood/youth explain the effects of pre-existing autism spectrum disorder (ASD) diagnoses on later suicidal thoughts and behaviors in adolescence/adulthood. We assessed internalizing and externalizing problems, bullying experiences, and executive functions (including cognitive flexibility, sustained attention, and spatial working memory) at an average baseline age of 13.4 years and suicidal thoughts and behaviors at an average follow-up age of 19.2 years among 129 autistic and 121 typically developing (TD) individuals. During the follow-up period in adolescence/adulthood, autistic individuals were more likely to report suicidal thoughts than TD individuals. Being bullied partially accounted for the relationship between a pre-existing ASD diagnosis and later-reported higher suicidal thoughts. Contrary to our hypothesis, higher (instead of lower) cognitive flexibility in some autistic young people appeared to partially explain their higher rates of suicidal thoughts compared with typically developing young people. The findings imply that school bullying prevention and tailored intervention programs for autistic people, especially those with higher cognitive flexibility, are warranted to reduce their risks of experiencing suicidal thoughts., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Individuals with autism spectrum disorder (ASD) often experience lifelong social communication challenges and are more vulnerable to school bullying. Addressing their social difficulties and school bullying requires evidence-based interventions. PEERS® (Program for the Education and Enrichment of Relational Skills) was adapted and translated for Taiwanese adolescents. This randomized controlled study aimed to examine the effectiveness of the Taiwanese version of PEERS® in reducing school bullying and enhancing social function among autistic adolescents. Twenty-one autistic adolescents (mean age 14.29 ± 1.67 years; female n = 733.33%) were randomized to a treatment group (TG, n = 10) or a delayed treatment control group (DTG, n = 11). The outcome measures (school bullying, social challenges, social skills knowledge, and social skills performance) were assessed at baseline, post-treatment, and follow-up. The group and time interaction analyses revealed greater magnitudes of reduction in general school bullying (p < 0.001), victimization (p < 0.001), perpetration (p = 0.012), social challenges (p = 0.001), and peer conflicts (p < 0.001), and improvement in social knowledge (p < 0.001) in the TG group than the DTG group. The findings suggest that the PEERS® program tailored for Taiwanese adolescents is effective in reducing school bullying, decreasing social challenges, and enhancing social skills among autistic adolescents, with very large effect sizes (Cohen's d ranging from 1.19 to 2.88). Consequently, participation in the PEERS® program is recommended for adolescents with social difficulties to improve their social communication and interactions to offset school bullying and other social challenges related to adverse outcomes., (© 2024 International Society for Autism Research, Wiley Periodicals LLC.)

Background: Quality of life (QoL) has been suggested as an indicator of outcomes in autistic adults. Factors associated with QoL in autistic individuals remain unclear. This study aims to examine the subjective QoL for autistic adults in Taiwan and investigate the determinants for different domains of QoL., Methods: The study comprised 90 autistic adults (aged 26.9, SD 7.3; males, 80.9%). We used Taiwanese version of World Health Organization Quality of Life-BREF to measure QoL. Four domains of QoL were compared with 61 non-autistic controls, including physical, psychological, social, and environment. To identify the correlates of QoL domains, we assessed IQ, personality trait, family support, anxiety/depressive symptoms, autistic severity, and sensory symptoms by various questionnaires, and assessed their association with QoL by correlation analyses and model selection., Results: Our results showed that autistic adults reported lower QoL on the World Health Organization Quality of Life (WHOQOL)-BREF across all domains. QoL was significantly associated with autistic symptom severity, harm avoidance, family support, sensory symptoms, anxiety, and depression, but not intelligence. Model selections revealed male sex, poor paternal support, autism severity, depression, anxiety, and sensory symptoms were associated with specific QoL domains., Conclusion: Findings supported lower QoL in autistic adults. Modifying the QoL correlates may improve life quality in autistic adults. Furthermore, our findings revealed the importance of sensory symptoms and paternal support in QoL of autistic adults, which was a novel finding in this population., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Lay Abstract: Childhood factors that predict real-world executive function in autism spectrum disorder during the transition into adulthood are largely unknown. This study aimed to identify the predictors for the behavioral and cognitive aspects of real-world executive function in late adolescent and young adult autistic populations. We followed up 289 autistic youth (mean age 11.6 years) and 203 non-autistic controls (10.7 years) to their ages of 16.9 and 15.8, respectively. The Behavior Rating Inventory of Executive Function scale was used to measure the real-world executive function at late adolescence and young adulthood at follow-up. Potential predictors such as autistic symptoms, inattention or hyperactivity symptoms, peer relationship, emotional symptoms, and parenting styles were assessed in childhood at first enrollment. The results showed that childhood inattention, withdrawn behaviors, social communication difficulties, and child-reported emotion and inattention/hyperactivity may predict real-world lower executive function in late adolescence and young adults with autism. When separating executive function into behavioral and cognitive aspects, we found that oppositional behaviors and peer problems were specific predictors for behavioral regulation and cognitive function, respectively. Our findings suggested that treating common predictors in childhood, such as inattention, may potentially improve real-world executive function in autism during the transition into adulthood., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.