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BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) has a high prevalence of co-occurring impaired self-regulation (dysregulation), exacerbating adverse outcomes. Neural correlates underlying impaired self-regulation in ADHD remain inconclusive. We aimed to investigate the impact of dysregulation on intrinsic functional connectivity (iFC) in children with ADHD and the correlation of iFC with dysregulation among children with ADHD relative to typically developing controls (TDC). METHODS: Resting-state functional MRI data of 71 children with ADHD (11.38 ± 2.44 years) and 117 age-matched TDC were used in the final analysis. We restricted our analyses to resting-state networks (RSNs) of interest derived from independent component analysis. Impaired self-regulation was estimated based on the Child Behavioral Checklist-Dysregulation Profile. RESULTS: Children with ADHD showed stronger iFC than TDC in the left frontoparietal network, somatomotor network (SMN), visual network (VIS), default-mode network (DMN), and dorsal attention network (DAN) (FWE-corrected alpha < 0.05). After adding dysregulation levels as an extra regressor, the ADHD group only showed stronger iFC in the VIS and SMN. ADHD children with high dysregulation had higher precuneus iFC within DMN than ADHD children with low dysregulation. Angular gyrus iFC within DMN was positively correlated with dysregulation in the ADHD group but negatively correlated with dysregulation in the TDC group. Functional network connectivity showed ADHD had a greater DMN-DAN connection than TDC, regardless of the dysregulation level. CONCLUSIONS: Our findings suggest that DMN connectivity may contribute to impaired self-regulation in ADHD. Impaired self-regulation should be considered categorical and dimensional moderators for the neural correlates of altered iFC in ADHD.
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AIM: To investigate parenting and mother-child interactions in unaffected siblings of autistic children. METHOD: This cross-sectional study enrolled 274 probands with a DSM-5 diagnosis of autism spectrum disorder (ASD) (87.4% male; mean [SD] age = 11 years 4 months [3 years 2 months]), their unaffected siblings (n = 274, 46.72% male; mean [SD] age = 11 years 3 months [3 years 4 months]), and 296 age-balanced and sex-balanced typically developing children (82.77% male; mean [SD] age = 11 years 3 months [2 years 8 months]). Maternal parenting styles and mother-child interactions were assessed using maternal reporting. RESULTS: Regardless of the child's age, maternal educational level, or presence of attention-deficit/hyperactivity disorder, autistic children received more overprotective and controlling parental behaviour than unaffected children. Correlates for parenting, mother-child interactions, and behavioural problems in the home setting in children with ASD and typically developing children were autistic traits, maternal anxiety and depressive symptoms, and maternal autistic characteristics; those in unaffected siblings were age, autistic traits, maternal educational level, and maternal autistic characteristics. INTERPRETATION: The diagnosis of ASD in a child can significantly influence maternal parenting behaviours, mother-child interactions, and the child's behavioural problems in the home setting. Furthermore, maternal anxiety or depressive symptoms, along with autistic characteristics in both mother and child, might shape parenting practices and exacerbate behavioural difficulties in autistic children.
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BACKGROUND: The sex-differential prevalence of attention-deficit/hyperactivity disorder (ADHD) varies across the lifespan, but little is known about sex differences in executive functions in adults with ADHD. METHODS: We assessed 261 adults, aged 18-40 years, diagnosed with ADHD (170 males [assigned at birth], aged 25.81 ± 5.49; 91 females, aged 27.76 ± 5.42) and 308 neurotypical adults (176 males, aged 24.62 ± 5.14; 132 female, aged 25.37 ± 5.42) via psychiatric interviews to confirm ADHD and other psychiatric diagnoses. They were assessed by the Cambridge Neuropsychological Testing Automated Battery (CANTAB) on Reaction Time (arousal/processing speed), Rapid Visual Information Processing (sustained attention), Spatial Span (spatial memory), Spatial Working Memory, Intradimentional/Extradimensional Shift (set-shifting), and Stocking of Cambridge (spatial planning). The primary analyses were adjusted for age, full-scale IQ, and co-occurring psychiatric conditions. RESULTS: Adults with ADHD had various co-occurring psychiatric conditions without sex differences in ADHD-neurotypical differences. Both adult males and females with ADHD performed poorer in all CANTAB tasks than same-sex neurotypical adults. Significant sex-moderating effects were observed in neuropsychological performance, including greater ADHD-neurotypical differences in arousal for females than males and in location memory for spatial tasks in males than females. CONCLUSION: There were no sex-moderating effects in the presence of co-occurring psychiatric conditions in adult ADHD. However, there were sex-moderating effects on how ADHD related to neuropsychological functioning in adulthood. ADHD was associated with more challenges in arousal/processing speed in females and more challenges in strategy use or inhibition in spatial memory in males.
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Trastorno por Déficit de Atención con Hiperactividad , Adulto , Recién Nacido , Humanos , Masculino , Femenino , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Función Ejecutiva/fisiología , Memoria a Corto Plazo/fisiología , Pruebas Neuropsicológicas , AtenciónRESUMEN
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.
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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.
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Trastorno del Espectro Autista , Predisposición Genética a la Enfermedad , Neurregulinas , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Trastorno del Espectro Autista/genética , Estudios de Casos y Controles , Exones/genética , Perfilación de la Expresión Génica , Frecuencia de los Genes , Estudios de Asociación Genética , Factores de Crecimiento Nervioso , Neurregulinas/genética , Neurregulinas/metabolismo , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Very few studies have investigated longitudinal clinical cohorts of attention-deficit/hyperactivity disorder (ADHD). Moreover, how baseline brain changes could affect the development of ADHD symptoms later in life remains elusive. Therefore, we aimed to fill this gap by exploring brain and clinical changes in youth with ADHD using a longitudinal design. METHODS: This prospective study consisted of 74 children and adolescents with ADHD and 50 age-, sex-, intelligence-matched typically developing controls (TDC), evaluated at baseline (aged 7-19 years) and re-evaluated 5.3 years later (a mean follow-up latency). We applied voxel-based morphometry to characterize brain structures, followed by both mass-univariate and multivariate structural covariance statistics to identify brain regions with significant diagnosis-by-time interactions from late childhood/adolescence to early adulthood. We used the cross-lagged panel model to investigate the longitudinal association between structural brain metrics and core ADHD symptoms. RESULTS: The mass-univariate statistic revealed significant diagnosis-by-time interactions in the right striatum and the sixth lobule of the cerebellum. This was expressed by increased striatal and decreased cerebellar volume in ADHD, while TDC showed inverse volume changes over time. The multivariate method showed significant diagnosis-by-time interactions in a structural covariance network consisting of the regions involved in the functional sensory-motor and default-mode networks. Higher baseline right striatal and cerebellar volumes were associated with elevated ADHD symptoms at follow-up. CONCLUSIONS: Our findings suggest a temporal association between the divergent development of striatal and cerebellar regions and dynamical ADHD phenotypic expression through young adulthood. These results highlight a potential brain marker of future outcomes.
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Trastorno por Déficit de Atención con Hiperactividad , Sustancia Gris , Adolescente , Humanos , Niño , Adulto Joven , Adulto , Sustancia Gris/diagnóstico por imagen , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Estudios Prospectivos , Encéfalo/diagnóstico por imagen , Corteza Cerebral , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: We aimed to identify important features of white matter microstructures collectively distinguishing individuals with attention-deficit/hyperactivity disorder (ADHD) from those without ADHD using a machine-learning approach. METHODS: Fifty-one ADHD patients and 60 typically developing controls (TDC) underwent diffusion spectrum imaging at two time points. We evaluated three models to classify ADHD and TDC using various machine-learning algorithms. Model 1 employed baseline white matter features of 45 white matter tracts at Time 1; Model 2 incorporated features from both time points; and Model 3 (main analysis) further included the relative rate of change per year of white matter tracts. RESULTS: The random forest algorithm demonstrated the best performance for classification. Model 1 achieved an area-under-the-curve (AUC) of 0.67. Model 3, incorporating Time 2 variables and relative rate of change per year, improved the performance (AUCâ¯=â¯0.73). In addition to identifying several white matter features at two time points, we found that the relative rate of change per year in the superior longitudinal fasciculus, frontal aslant tract, stria terminalis, inferior fronto-occipital fasciculus, thalamic and striatal tracts, and other tracts involving sensorimotor regions are important features of ADHD. A higher relative change rate in certain tracts was associated with greater improvement in visual attention, spatial short-term memory, and spatial working memory. CONCLUSIONS: Our findings support the significant diagnostic value of white matter microstructure and the developmental change rates of specific tracts, reflecting deviations from typical development trajectories, in identifying ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , Aprendizaje Automático , Sustancia Blanca , Humanos , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Trastorno por Déficit de Atención con Hiperactividad/patología , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Masculino , Femenino , Estudios Longitudinales , Niño , Adolescente , Imagen de Difusión Tensora/métodosRESUMEN
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.
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BACKGROUND: This study aimed to estimate the population-attributable fraction (PAF) of psychiatric and physical disorders for suicide among older adults, focusing on sex- and age-specific factors. METHODS: Data from Taiwan's National Health Insurance Research Data and National Death Registry included 9136 cases of suicide in individuals aged 65+, with 89,439 matched controls. Physical and psychiatric disorders were identified through diagnostic records. Conditional logistic regression assessed risk factors, and PAF was calculated using disorder prevalence and adjusted odds ratios. RESULTS: Major suicide risk factors among older adults were depressive disorders, anxiety disorders, and sleep disorders. Physical disorders like hypertension, peptic ulcers, and cancer also showed significant PAF values. The combined PAF of physical disorders equaled that of psychiatric disorders. Psychiatric disorders had a greater impact on women and the youngest-old adults, while physical disorders had a higher contribution among men, middle-old adults, and oldest-old adults. LIMITATIONS: Relying solely on claim data to identify psychiatric and physical disorders may underestimate their prevalence and associations with suicide due to unrecorded cases of individuals not seeking help and the absence of key risk factors like social isolation and family support. CONCLUSIONS: This study identifies preventable or treatable risk factors for older adult suicide, emphasizing the need to target specific psychiatric and physical disorders in suicide prevention efforts while taking into account sex- and age-specific considerations. It also underscores the importance of establishing social welfare support systems to address the unique challenges older adults face.
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Trastornos Mentales , Suicidio , Humanos , Taiwán/epidemiología , Masculino , Femenino , Anciano , Suicidio/estadística & datos numéricos , Factores de Riesgo , Anciano de 80 o más Años , Trastornos Mentales/epidemiología , Factores Sexuales , Prevalencia , Factores de Edad , Trastornos de Ansiedad/epidemiología , Trastorno Depresivo/epidemiología , Trastornos del Sueño-Vigilia/epidemiología , Neoplasias/epidemiología , Neoplasias/psicología , Úlcera Péptica/epidemiología , Hipertensión/epidemiologíaRESUMEN
BACKGROUND: Little is known about how clinical features prospectively influence peer relationships in autistic populations. AIMS: This study investigated the clinical symptoms mediating the link between autism spectrum disorder (ASD) diagnosis and peer relationships at follow-up, i.e. the second time evaluation of this study. METHODS: The sample consisted of 366 autistic youths and 134 non-autistic comparisons. The autistic traits and emotional/behavioral problems were measured at baseline by Social Responsiveness Scale (SRS) and Child Behavior Checklist (CBCL). The interactions and problems with peers were assessed by the Social Adjustment Inventory for Children and Adolescents (SAICA) at follow-up. RESULTS: Each subscore of SRS and CBCL showed significant mediation effects. Multiple mediation analyses showed atypical social communication, social awareness problems, and delinquent behaviors mediated the link from ASD to less active peer interactions after controlling for sex, age, and IQ. Moreover, atypical social communication, social-emotional problems, and attention difficulties predicted problems with peers. After considering these mediation effects, the diagnosis of ASD still demonstrated a significantly direct effect on peer relationships at follow-up. CONCLUSIONS AND IMPLICATIONS: Our findings support that social-related autistic features, attention problems, and delinquent behaviors mediated a link between ASD and peer relationships. These mediators are potential measures for improving interactions and decreasing difficulties with peers in the autistic population.
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Trastorno del Espectro Autista , Grupo Paritario , Humanos , Masculino , Femenino , Niño , Trastorno del Espectro Autista/psicología , Adolescente , Estudios de Seguimiento , Conducta Social , Relaciones Interpersonales , Estudios de Casos y Controles , Emociones , Problema de Conducta/psicología , Interacción Social , Comunicación , Delincuencia Juvenil/psicología , Ajuste Social , Síntomas Conductuales/psicologíaRESUMEN
Whether brain stimulation could modulate brain structure in autism remains unknown. This study explored the impact of continuous theta burst stimulation (cTBS) over the left dorsolateral prefrontal cortex (DLPFC) on white matter macro/microstructure in intellectually able children and emerging adults with autism. Sixty autistic participants were randomized (30 active) and received active or sham cTBS for eight weeks twice per week, 16 total sessions using a double-blind (participant-, rater-, analyst-blinded) design. All participants received high-angular resolution diffusion MR imaging at baseline and week 8. Twenty-eight participants in the active group and twenty-seven in the sham group with good imaging quality entered the final analysis. With longitudinal fixel-based analysis and network-based statistics, we found no significant difference between the active and sham groups in changes of white matter macro/microstructure and connections following cTBS. In addition, we found no association between baseline white matter macro/microstructure and autistic symptom changes from baseline to week 8 in the active group. In conclusion, we did not find a significant impact of left DLPFC cTBS on white matter macro/microstructure and connections in children and emerging adults with autism. These findings need to be interpreted in the context that the current intellectually able cohort in a single university hospital site limits the generalizability. Future studies are required to investigate if higher stimulation intensities and/or doses, other personal factors, or rTMS parameters might confer significant brain structural changes visible on MRI in ASD.
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Importance: With the rising prevalence of mental disorders among children and adolescents, identifying modifiable associations is critical. Objective: To examine the association between physical fitness and mental disorder risks. Design, Setting, and Participants: This nationwide cohort study used data from the Taiwan National Student Fitness Tests and National Health Insurance Research Databases from January 1, 2009 to December 31, 2019. Participants were divided into 2 cohorts targeting anxiety and depression (1â¯996â¯633 participants) and attention-deficit/hyperactivity disorder (ADHD; 1â¯920â¯596 participants). Participants were aged 10 to 11 years at study entry and followed up for at least 3 years, had a nearly equal gender distribution, and an average follow-up of 6 years. Data were analyzed from October 2022 to February 2024. Exposures: Assessments of physical fitness included cardiorespiratory fitness (CF), muscular endurance (ME), muscular power (MP), and flexibility, measured through an 800-m run time, bent-leg curl-ups, standing broad jump, and sit-and-reach test, respectively. Main Outcomes and Measures: Kaplan-Meier method calculated the cumulative incidence of anxiety, depression, and ADHD across fitness quartiles. Additionally, multivariable Cox proportional hazards models were used that included all 4 fitness components and explored sex and income as modifiers. Results: The anxiety and depression cohort had 1â¯996â¯633 participants (1â¯035â¯411 participants were male [51.9%], and the median [IQR] age was 10.6 [10.3-11.0] years), while the ADHD cohort had 1â¯920â¯596 (975â¯568 participants were male [51.9%], and the median [IQR] age was 10.6 [10.3-11.0] years). Cumulative incidence of mental disorders was lower among participants in better-performing fitness quartiles, suggesting a dose-dependent association. Gender-specific analyses, controlling for confounders, revealed that improved CF, indicated by a 30-second decrease in run times, was associated with reduced risks of anxiety, depression, and ADHD in female participants, and lower risks of anxiety and ADHD in male participants (adjusted hazard ratio [aHR] for ADHD risk for female participants, 0.92; 95% CI, 0.90-0.94; P < .001; for male participants, 0.93; 95% CI, 0.92-0.94; P < .001). Enhanced ME, marked by an increase of 5 curl-ups per minute, was associated with decreased risks of depression and ADHD in female participants, and lower anxiety and ADHD risks in male participants (aHR for ADHD risk for female participants, 0.94; 95% CI, 0.92-0.97; P < .001; for male participants, 0.96; 95% CI, 0.95-0.97; P < .001). Improved MP, reflected by a 20-cm increase in jump distance, was associated with reduced risks of anxiety and ADHD in female participants and reduced anxiety, depression, and ADHD in male participants (aHR for ADHD risk for female participants, 0.95; 95% CI, 0.91-1.00; P = .04; for male participants, 0.96; 95% CI, 0.94-0.99; P = .001). Conclusions and Relevance: This study highlights the potential protective role of cardiorespiratory fitness, muscular endurance, and muscular power in preventing the onset of mental disorders. It warrants further investigation of the effectiveness of physical fitness programs as a preventive measure for mental disorders among children and adolescents.
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Trastorno por Déficit de Atención con Hiperactividad , Aptitud Física , Humanos , Masculino , Femenino , Niño , Aptitud Física/fisiología , Taiwán/epidemiología , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastornos Mentales/epidemiología , Factores de Riesgo , Incidencia , Estudios de CohortesRESUMEN
BACKGROUND: Few previous studies have established Snaith-Hamilton Pleasure Scale (SHAPS) cut-off values using receiver operating characteristic curve analysis and applied these values to compare predictors of anhedonia between clinical and nonclinical groups. AIMS: To determine the optimal cut-off values for the SHAPS and use them to identify predictors of anhedonia in clinical and nonclinical groups in Taiwan. METHOD: This cross-sectional and correlational study used convenience sampling to recruit 160 patients from three hospitals and 412 students from two universities in northern Taiwan. Data analysis included receiver operating characteristic curve, univariate and multivariate analyses. RESULTS: The optimal SHAPS cut-off values were 29.5 and 23.5 for the clinical and nonclinical groups, respectively. Moreover, two-stage analysis revealed that participants in the clinical group who perceived themselves as nondepressed, and participants in the nonclinical group who did not skip classes and whose fathers exhibited higher levels of care and protection were less likely to attain the cut-off values. Conversely, participants in the nonclinical group who reported lower academic satisfaction and were unwilling to seek help from family or friends were more likely to attain the cut-off values. CONCLUSIONS: Our findings highlight the importance of optimal cut-off values in screening for depression risk within clinical and nonclinical groups. Accordingly, the development of comprehensive, individualised programmes to monitor variation trends in SHAPS scores and relevant predictors of anhedonia across different target populations is crucial.