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).

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.

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.

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.

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.

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.

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.

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.

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.

Youth suicide rates have increased markedly in some countries. This study aimed to estimate the population-attributable risk of psychiatric disorders associated with suicide among Taiwanese youth aged 10–24 years.

Data were obtained from the National Death Registry and National Health Insurance (NHI) claims database between 2007 and 2019. Youth who died by suicide were included, and comparisons, 1:10 matched by age and sex, were randomly selected from the Registry for NHI beneficiaries. We used multivariable logistic regression to estimate suicide odds ratios for psychiatric disorders. The population-attributable fractions (PAF) were calculated for each psychiatric disorder.

A total of 2345 youth suicide and 23 450 comparisons were included. Overall, 44.8% of suicides had a psychiatric disorder, while only 7.9% of the comparisons had a psychiatric disorder. The combined PAF for all psychiatric disorders was 55.9%. The top three psychiatric conditions of the largest PAFs were major depressive disorder, dysthymia, and sleep disorder. In the analysis stratified by sex, the combined PAF was 45.5% for males and 69.2% for females. The PAF among young adults aged 20–24 years (57.0%) was higher than among adolescents aged 10–19 years (48.0%).

Our findings of high PAF from major depressive disorder, dysthymia, and sleep disorder to youth suicides suggest that youth suicide prevention that focuses on detecting and treating mental illness may usefully target these disorders.

Despite the fact that social deficits among individuals with autism spectrum disorder (ASD) are lifelong and impact many aspects of personal functioning, evidence-based programs for social skills training were not available until recently. The Program for the Education and Enrichment of Relational Skills (PEERS®) has been shown to effectively improve social skills for adolescents on the spectrum across different social cultures. However, the effectiveness for young adults beyond North America has yet to be examined. This study aimed to investigate the effectiveness of the PEERS intervention in Taiwanese young adults with ASD, and examine its durability and clinical correlates.

We recruited 82 cognitively-able young adults with ASD, randomized to the PEERS treatment or treatment-as-usual.

Following treatment, significant improvement was found in aspects of social deficits, autism severity, social interaction anxiety, empathy, and social skills knowledge either by self-report or coach-report. Additionally, communicative behaviors rated by observers improved throughout the sessions, showing a trend toward more appropriate eye contact, gestures, facial expression during conversation, and appropriate maintenance of conversation and reciprocity. Most effects maintained at 3-month and 6-month follow-ups. The improvement of social deficits was positively correlated with baseline severity, while gains in social skills knowledge were positively correlated with IQ. The improvement of social deficits, autism severity, and empathy were positively correlated with each other.

Overall, the PEERS intervention appears to effectively improve social functioning in Taiwanese young adults with ASD. Improvement of social response and knowledge may be predicted by baseline severity and intelligence respectively.

Individuals with attention-deficit hyperactivity disorder (ADHD) often display over-response to stimuli that are irrelevant to the ongoing task, and their attentional abilities disproportionately worsen in the presence of competing stimuli. Auditory event-related potentials (ERPs) such as mismatch negativity (MMN) and P3a using the passive oddball paradigm have been studied in children and adolescents with ADHD. Still, there is no such data for adults with ADHD. This study aimed to compare the MMN and P3a and their clinical and neurocognitive correlations between drug-naive adults with ADHD and control adults.

We recruited 52 adults with ADHD (26.5 ± 6.2 years), and 62 age-matched controls (25.6 ± 5.6 years). They received the psychiatric interviews, auditory ERP, the Conners' continuous performance test (CCPT), and the Cambridge gambling test (CGT). They also completed the questionnaires about ADHD symptoms and real-world executive functions. MMN and P3a were assessed during a passive duration-deviant auditory oddball paradigm from the midline electrodes Cz.

Adults with ADHD demonstrated smaller Cz MMN amplitude, more severe ADHD symptoms, poorer attention profiles (CCPT), and a wide range of executive dysfunctions than controls. As for the correlates, Cz peak amplitude of MMN correlated with inattention symptoms, executive dysfunctions, attentional vigilance (CCPT), and decision-making (CGT) in ADHD adults but only with decision-making in controls.

Our findings that smaller amplitude of MMN and its differential associated pattern with inattention, real-world executive dysfunction, and decision-making, in drug-naive adults with ADHD from adult controls, provide evidence to support the potential electrophysiological biomarker for adult ADHD.

Although aberrant intrinsic functional connectivity has been reported in attention-deficit/hyperactivity disorder (ADHD), we have a limited understanding of whether connectivity alterations are related to the familial risk of ADHD.

Fifty-three probands with ADHD, their unaffected siblings (n = 53) and typically developing controls (n = 53) underwent resting-state functional magnetic resonance imaging scans. A seed-based approach with the bilateral precuneus/posterior cingulate cortex (PCC) was used to derive a whole-brain functional connectivity map in each subject. The differences in functional connectivity among the three groups were tested with one-way ANOVA using randomized permutation. Comparisons between two groups were also performed to examine the increase or decrease in connectivity. The severity of ADHD symptoms was used to identify brain regions where symptom severity is correlated to the strength of intrinsic functional connectivity.

When compared to controls, both probands and unaffected siblings showed increased functional connectivity in the left insula and left inferior frontal gyrus. The connectivity in these regions was linked to better performance in response inhibition in the control group but absent in other groups. Higher ADHD symptom severity was correlated with increased functional connectivity in bilateral fronto-parietal-temporal regions only noted in probands with ADHD.

Alterations in resting-state functional connectivities with the precuneus/PCC, hubs of default-mode network, account for the underlying familial risks of ADHD. Since the left insula and left inferior frontal gyri are key regions of the salience and frontoparietal network, respectively, future studies focusing on alterations of cross-network functional connectivity as the familial risk of ADHD are suggested.

Executive dysfunction is one of the main cognitive theories of autism spectrum disorder (ASD). Despite evidence of deficits in executive functions in individuals with ASD, little is known about executive dysfunctions as candidate cognitive endophenotypes for ASD. In this study, we investigated executive functions in youths with ASD, their unaffected siblings and typically developing controls (TDC).

We recruited 240 youths with a clinical diagnosis of ASD (aged 6–18 years), 147 unaffected siblings of ASD youths, and 240 TDC youths. TDC youths were recruited based on the age and sex distribution of the ASD youths. Participants were assessed using the verbal Digit Span test and four executive function tasks from the Cambridge Neuropsychological Test Automated Battery, including Intra-dimensional/Extra-dimensional Shift (I/ED), Spatial Span (SSP), Spatial Working Memory (SWM), and Stocking of Cambridge (SoC).

ASD youths, relative to TDC, performed significantly worse in executive function tasks assessing verbal working memory (forward and backward digit span), set-shifting (I/ED), visuospatial working memory (SSP, SWM), and planning/problem solving (SoC). Furthermore, unaffected siblings, relative to TDC, performed worse in forward and backward digit recalls and made more errors in SWM. These results were independent of the effects of age, sex, IQ, and symptoms of attention-deficit/hyperactivity disorder.

Our findings support impaired executive functions in youths with ASD. However, unaffected siblings were mostly unimpaired except in the areas of verbal and spatial working memory, which may be potential cognitive endophenotypes for ASD.

The dopamine transporter gene (DAT1), striatal network dysfunction, and visual memory deficits have been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine the effects of the DAT1 rs27048 (C)/rs429699 (T) haplotype on striatal functional connectivity and visual memory performance in youths with ADHD.

After excluding those who had excessive head motion, a total of 96 drug-naïve youths with ADHD and 114 typically developing (TD) youths were assessed with the resting-state functional magnetic resonance imaging and the delayed matching to sample (DMS) task for visual memory. We examined the effects of ADHD, DAT1 CT haplotype, and the ADHD × CT haplotype interaction on the functional connectivity of five striatal seeds. We also correlated visual memory performance with the functional connectivity of striatal subregions, which showed significant diagnosis × genotype interactions.

Compared with TD youths, ADHD youths showed significant hypoconnectivity of the left dorsal caudate (DC) with bilateral sensorimotor clusters. Significant diagnosis × genotype interactions were found in the connectivity between the left DC and the right sensorimotor cluster, and between the right DC and the left dorsolateral prefrontal/bilateral anterior cingulate clusters. Furthermore, the connectivity of the left DC showing significant diagnosis × genotype interactions was associated with DMS performance in youths with ADHD who carried the DAT1 CT haplotype.

A novel gene-brain-behavior association between the left DC functional connectivity and visual memory performance in ADHD youths with the DAT1 rs27048 (C)/rs429699 (T) haplotype suggests a differential effect of DAT1 genotype altering specific brain function causing neuropsychological dysfunction in ADHD.

Although the literature documents low executive functions and sleep deficits in individuals with autism spectrum disorder or subclinical autistic traits, no study has simultaneously examined their relationships in the general child population. This study aimed to examine whether autistic traits impacted real-world executive functions through insufficient sleep in a nationally representative sample of children.

This was a national survey of 6832 primary and secondary school students, aged 8–14 years old, with equal sex distribution (3479 boys, 50.8%). Parents reported their child's nocturnal sleep duration and the need for sleep to maintain their daytime function and the Social Responsiveness Scale and the Behavior Rating Inventory of Executive Function (BRIEF) for their children's autistic traits and real-world executive functions, respectively.

We found that autistic traits exerted indirect effects on real-world executive functions through sleep deficits, independent of sex, and age. Moreover, such an indirect effect was observed only from restricted and repetitive behaviors to executive functions through sleep deficits, but not in the other components of autistic traits (i.e. social communication and interaction).

Our novel findings underscore the importance of sleep and autistic traits in executive functions and suggest potential mechanisms that may underlie the observed correlational structure among autistic behaviors, sleep deficits, and low executive function performance.

Brain structural alterations are frequently observed in probands with attention-deficit/hyperactivity disorder (ADHD). Here we examined the microstructural integrity of 76 white matter tracts among unaffected siblings of patients with ADHD to evaluate the potential familial risk and its association with clinical and neuropsychological manifestations.

The comparison groups included medication-naïve ADHD probands (n = 50), their unaffected siblings (n = 50) and typically developing controls (n = 50, age-and-sex matched with ADHD probands). Whole brain tractography was reconstructed automatically by tract-based analysis of diffusion spectrum imaging (DSI). Microstructural properties of white matter tracts were represented by the values of generalized fractional anisotropy (GFA), fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD).

Compared to the control group, ADHD probands showed higher AD values in the perpendicular fasciculus, superior longitudinal fasciculus I, corticospinal tract, and corpus callosum. The AD values of unaffected siblings were in the intermediate position between those of the ADHD and control groups. These AD values were significantly associated with ADHD symptoms, sustained attention and working memory, for all white matter tracks evaluated except for the perpendicular fasciculus. Higher FA and lower RD values in the right frontostriatal tract connecting ventrolateral prefrontal cortex (FS-VLPFC) were associated with better performance in spatial span only in the unaffected sibling group.

Abnormal AD values of specific white matter tracts among unaffected siblings of ADHD probands suggest the presence of familial risk in this population. The right FS-VLPFC may have a role in preventing the expression of the ADHD-related behavioral phenotype.

NCT01682915

There has been a lack of prevalence estimates of DSM-5 mental disorders in child populations at the national level worldwide. This study estimated the lifetime and 6-month prevalence of mental disorders according to the DSM-5 diagnostic criteria in Taiwanese children.

Taiwan's National Epidemiological Study of Child Mental Disorders used the stratified cluster sampling to select 69 schools in Taiwan resulting in a nationally representative sample of 4816 children in grades 3 (n = 1352), 5 (n = 1297) and 7 (n = 2167). All the participants underwent face-to-face psychiatric interviews using the Kiddie-Schedule for Affective Disorders and Schizophrenia-Epidemiological version, modified for the DSM-5, and they and their parents completed questionnaires. The inverse probability censoring weighting (IPCW)-adjusted prevalence was reported to minimise non-response bias.

The IPCW-adjusted prevalence rates of mental disorders decreased by 0.1–0.5% than raw weighted prevalence. The IPCW-adjusted weighted lifetime and 6-month prevalence rates for overall mental disorders were 31.6 and 25.0%, respectively. The most prevalent mental disorders (lifetime, 6-month) were anxiety disorders (15.2, 12.0%) and attention-deficit hyperactivity disorder (10.1, 8.7%), followed by sleep disorders, tic disorders, oppositional defiant disorder and autism spectrum disorder. The prevalence rates of new DSM-5 mental disorders, avoidant/restrictive food intake disorder and disruptive mood dysregulation disorder were low (<1%).

Our findings, similar to the DSM-IV prevalence rates reported in Western countries, indicate that DSM-5 mental disorders are common in the Taiwanese child population and suggest the need for public awareness, early detection and prevention.

Our knowledge about the developmental change of neuropsychological functioning in attention-deficit/hyperactivity disorder (ADHD) is limited. This prospective longitudinal study examined the changes in neuropsychological functions and their associations with the changes of ADHD symptoms across the developmental stages from early adolescence to young adulthood.

We followed up 53 individuals diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) ADHD during childhood (mean age 12.77 years at time 1, 19.81 years at time 2) and 50 non-ADHD controls (mean age 12.80 years at time 1, 19.36 years at time 2) with repeated psychiatric interviews at two time points to confirm ADHD and other psychiatric diagnoses. Neuropsychological functions with high- and low-executive demands, measured by the Cambridge Neuropsychological Testing Automated Battery (CANTAB) at two time points, were compared.

Both groups showed improvements in all neuropsychological tasks except reaction time in the ADHD group. Despite having a greater improvement in spatial working memory (SWM) than controls, individuals with ADHD still performed worse in various neuropsychological tasks than controls at follow-up. Better baseline intra-dimension/extra-dimension shift and parental occupation predicted fewer ADHD symptoms at follow-up independent of baseline ADHD symptoms. The degree of ADHD symptom reduction was not significantly linearly correlated to the magnitude of neuropsychological function improvement.

Individuals with ADHD and controls had parallel developments in neuropsychological functioning, except a catch-up in SWM in ADHD. Almost all neuropsychological functions herein were still impaired in ADHD at late adolescence/young adulthood. There may be a threshold (i.e. non-linear) relationship between neuropsychological functioning and ADHD symptoms.

Childhood-onset attention-deficit hyperactivity disorder (ADHD) in adults is clinically heterogeneous and commonly presents with different patterns of cognitive deficits. It is unclear if this clinical heterogeneity expresses a dimensional or categorical difference in ADHD.

We first studied differences in functional connectivity in multi-echo resting-state functional magnetic resonance imaging (rs-fMRI) acquired from 80 medication-naïve adults with ADHD and 123 matched healthy controls. We then used canonical correlation analysis (CCA) to identify latent relationships between symptoms and patterns of altered functional connectivity (dimensional biotype) in patients. Clustering methods were implemented to test if the individual associations between resting-state brain connectivity and symptoms reflected a non-overlapping categorical biotype.

Adults with ADHD showed stronger functional connectivity compared to healthy controls, predominantly between the default-mode, cingulo-opercular and subcortical networks. CCA identified a single mode of brain–symptom co-variation, corresponding to an ADHD dimensional biotype. This dimensional biotype is characterized by a unique combination of altered connectivity correlating with symptoms of hyperactivity-impulsivity, inattention, and intelligence. Clustering analyses did not support the existence of distinct categorical biotypes of adult ADHD.

Overall, our data advance a novel finding that the reduced functional segregation between default-mode and cognitive control networks supports a clinically important dimensional biotype of childhood-onset adult ADHD. Despite the heterogeneity of its presentation, our work suggests that childhood-onset adult ADHD is a single disorder characterized by dimensional brain–symptom mediators.

The long-term outcome of patients with both diabetes and schizophrenia remains unclear.

To explore whether having schizophrenia increases the risk of advanced complications and mortality in people with diabetes.

This is a population-based matched cohort study using Taiwan's National Health Insurance Research Database. A total of 11 247 participants with diabetes and schizophrenia and 11 247 participants with diabetes but not schizophrenia were enrolled. We used Cox proportional hazard models to determine the effect of schizophrenia on macrovascular and microvascular complications, and all-cause mortality.

The adjusted hazard ratios were 1.49 (95% CI 1.32–1.68) for macrovascular complications, 1.05 (95% CI 0.91–1.21) for microvascular complications and 3.68 (95% CI 3.21–4.22) for all-cause mortality in patients with diabetes and schizophrenia compared with those patients with diabetes but not schizophrenia.

Patients with both diabetes and schizophrenia had an increased risk of macrovascular complications and all-cause mortality but did not have statistically significant elevated risk of microvascular complications.