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Objective: The efficacy and safety of atomoxetine was assessed in adult ADHD patients from Japan, Korea, and Taiwan in this first placebo-controlled Asian clinical study in adults of an ADHD medication. Method: Atomoxetine was compared with placebo (195 atomoxetine, 196 placebo) over 10 weeks. The change from baseline to endpoint and changes over time in the Conners’ Adult ADHD Rating Scale–Investigator Rated: Screening Version total score (CAARS-Inv: SV total score) were assessed along with changes in quality of life (QoL) and executive function. Results: Atomoxetine treatment resulted in a mean reduction of −14.3 (placebo, −8.8) in CAARS-Inv: SV total score and a steady increase of between-group differences from Week 2. Improvements in QoL and executive functioning were also observed. Treatment-emergent adverse events leading to discontinuation were infrequent (atomoxetine: 5.2%, placebo: 1.5%). Conclusion: Atomoxetine was tolerable and effective in improving QoL and executive function as well as ameliorating core ADHD symptoms in adult Asian patients.

BackgroundImpaired executive function (EF) is suggested to be one of the core features in individuals with autism spectrum disorders (ASD); however, little is known about whether the extent of worse EF in ASD than typically developing (TD) controls is age-dependent. We used age-stratified analysis to reveal this issue.MethodWe assessed 111 youths with ASD (aged 12.5 ± 2.8 years, male 94.6%) and 114 age-, and sex-matched TD controls with Digit Span and four EF tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Spatial Span (SSP), Spatial Working Memory (SWM), Stockings of Cambridge (SOC), and Intradimensional/Extradimensional Shift Test (I/ED).ResultsCompared to TD controls, youths with ASD performed poorer on the Digit Span, SWM, SOC, and I/ED tasks. The performance of all the tasks improved with age for both groups. Age-stratified analyses were conducted due to significant age × group interactions in visuospatial planning (SOC) and set-shifting (I/ED) and showed that poorer performance on these two tasks in ASD than TD controls was found only in the child (aged 8–12 years) rather than the adolescent (aged 13–18 years) group. By contrast, youths with ASD had impaired working memory, regardless of age. The increased magnitude of group difference in visuospatial planning (SOC) with increased task demands differed between the two age groups but no age moderating effect on spatial working memory.ConclusionsOur findings support deficits in visuospatial working memory and planning in youths with ASD; however, worse performance in set-shifting may only be demonstrated in children with ASD.

Objective: Intra-individual variability in reaction time (IIV-RT) is common in individuals with attention-deficit/hyperactivity disorder (ADHD). It can be improved by stimulants. However, the effects of atomoxetine on IIV-RT are inconclusive. We aimed to investigate the effects of atomoxetine on IIV-RT, and directly compared its efficacy with methylphenidate in adults with ADHD. Methods: An 8–10 week, open-label, head-to-head, randomized clinical trial was conducted in 52 drug-naïve adults with ADHD, who were randomly assigned to two treatment groups: immediate-release methylphenidate ( n=26) thrice daily (10–20 mg per dose) and atomoxetine once daily ( n=26) (0.5–1.2 mg/kg/day). IIV-RT, derived from the Conners’ continuous performance test (CCPT), was represented by the Gaussian (reaction time standard error, RTSE) and ex-Gaussian models (sigma and tau). Other neuropsychological functions, including response errors and mean of reaction time, were also measured. Participants received CCPT assessments at baseline and week 8-10 (60.4±6.3 days). Results: We found comparable improvements in performances of CCPT between the immediate-release methylphenidate- and atomoxetine-treated groups. Both medications significantly improved IIV-RT in terms of reducing tau values with comparable efficacy. In addition, both medications significantly improved inhibitory control by reducing commission errors. Conclusion: Our results provide evidence to support that atomoxetine could improve IIV-RT and inhibitory control, of comparable efficacy with immediate-release methylphenidate, in drug-naïve adults with ADHD. Shared and unique mechanisms underpinning these medication effects on IIV-RT awaits further investigation.

Individuals with autism spectrum disorders (ASD) have aberrant neural activity during semantic judgments. We aimed to examine age-dependent neural correlates of semantic processing in boys with ASD as compared to typically developing boys (TD). We used functional MRI to investigate 37 boys with ASD (mean age = 13.3 years, standard deviation = 2.4) and 35 age-, sex-, Intelligence quotient (IQ)- and handedness-matched TD boys (mean age = 13.3 years, standard deviation = 2.7) from age 8 to 18 years. Participants had to indicate whether pairs of Chinese characters presented visually were related in meaning. Group (ASD, TD) × Age (Old, Young) ANOVA was used to examine the difference of age-related changes. Direct comparisons between the adolescent group and the child group were also performed. The behavioral results showed that the ASD group had lower accuracy in the related condition relative to the TD group. The neuroimaging results showed greater activation in the cuneus and less activation in the left inferior frontal gyrus in boys with ASD than TD boys. Children with ASD produced greater activation in the cuneus than TD children. Adolescents with ASD showed reduced left IFG activation as compared to TD adolescents. Our findings suggest that TD boys may engage more in higher-level processing of retrieving or selecting semantic features while boys with ASD may rely more on lower-level visual processing during semantic judgments. The findings imply different functional organizations of the semantic system between the two groups. Autism Res 2016, 9: 1263-1273. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

In addition to the essential features of autism spectrum disorder (ASD), namely social communication deficits and repetitive behaviors, individuals with ASD may suffer from working memory deficits and an altered default-mode network (DMN). We hypothesized that an altered DMN is related to working memory deficits in those with ASD. A total of 37 adolescents with ASD and 36 age- and IQ-matched typically developing (TD) controls were analyzed. Visuospatial working memory performance was assessed using pattern recognition memory (PRM), spatial recognition memory (SRM), and paired-associates learning (PAL) tasks. The intrinsic functional connectivity (iFC) of the DMN was indexed by the temporal correlations between the resting-state functional magnetic resonance imaging signals of pairs of DMN regions, including those between the posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC) and between the PCC and parahippocampi (PHG). The corresponding structural connectivity of the DMN was indexed by the generalized fractional anisotropy (GFA) of the dorsal and ventral cingulum bundles on the basis of diffusion spectrum imaging data. The results showed that ASD adolescents exhibited delayed correct responses in PRM and SRM tasks and committed more errors in the PAL task than the TD controls did. The delayed responses during the PRM and SRM tasks were negatively correlated with bilateral PCC-mPFC iFCs, and PAL performance was negatively correlated with right PCC-PHG iFC in ASD adolescents. Furthermore, ASD adolescents showed significant lower GFA in the right cingulum bundles than the TD group did; the GFA value was negatively correlated with SRM performance in ASD. Our results provide empirical evidence for deficient visuospatial working memory and corresponding neural correlates within the DMN in adolescents with ASD. Autism Res 2016, 9: 1058-1072. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Objective Antipsychotic drug use is an established risk factor for the development of type 2 diabetes mellitus. However, the effect of antipsychotic drug on the progression of diabetes complications remains unclear. This study aimed to explore the association between antipsychotic treatment and advanced diabetes outcome among schizophrenia patients with type 2 diabetes. Methods The authors conducted a retrospective cohort study using Taiwan's universal health insurance database. A total of 17 629 schizophrenia patients with newly-diagnosed diabetes were enrolled. The mean duration of follow-up, after excluding the first 6-month observation period, was 4.8 years, ranged from 1 month to 11.5 years. Antipsychotic treatment patterns within a 6-month time window were classified into none, irregular use, and regular use. Antipsychotics were further categorized into the high, intermediate, and low metabolic risks. The status of exposure was treated as time-dependent variables. The outcomes measures included any advanced diabetes complications, macrovascular and microvascular complications, and all-cause mortality. Results Compared to no antipsychotic treatment in the past 6 months, regular antipsychotic use was associated with a lower risk of any advanced diabetes complications (adjusted hazard ratio, aHR = 0.81, 95% CI = 0.69-0.95), macrovascular complications (aHR = 0.80, 95% CI = 0.66-0.97), and all-cause mortality (aHR = 0.73, 95% CI = 0.62-0.85). The hazard ratios for advanced diabetes complications with regular use of antipsychotics with a high, intermediate, and low metabolic risk were 0.69 (95% CI = 0.53-0.91), 0.82 (95% CI = 0.68-0.99), and 0.85 (95% CI = 0.70-1.02), respectively. Conclusions Regular antipsychotic treatment in the past 6 months was associated with reduced risks of any diabetes complications, compared to no antipsychotic treatment.

Methylphenidate and atomoxetine are effective in treating attention-deficit/hyperactivity disorder (ADHD) with underlying distinct pharmacological mechanisms. To relate neural mechanisms to clinical response, we conducted a comparative trial to differentiate the changes in brain activation of drug-naïve children with ADHD when performing neuropsychological tasks after 12 weeks of pharmacotherapy. We randomized 50 drug-naïve children with ADHD, aged 7-17, to treatment with methylphenidate (n=25) or atomoxetine (n=25). These children were scanned twice with functional magnetic resonance imaging (fMRI) during the counting Stroop task before and after treatment. Focused attention and impulsivity were assessed twice by using the Conner's Continuous Performance Test (CCPT). The final sample for fMRI analysis comprised 20 in the methylphenidate group and 22 in the atomoxetine group. Atomoxetine decreased activations in the dorsal anterior cingulate cortex and dorsolateral prefrontal cortex, which correlated with improvement in focused attention assessed by the CCPT. In contrast, methylphenidate increased activations in the inferior frontal gyrus, which correlated with the decreasing severity of impulsivity assessed by the CCPT. The current findings suggest that differential therapeutic effects on neuronal changes induced by 12-week treatment atomoxetine and methylphenidate may contribute to behavioral improvement.

The newly published Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) elevates the threshold of the ADHD age-of-onset criterion from 7 to 12 years. This study evaluated the quality of life and functional impairment of adults with ADHD who had symptoms onset by or after 7 years and examined the mediation effect of family function and anxiety/depression symptoms between ADHD diagnosis and quality of life and functional impairment. We assessed 189 adults with ADHD and 153 non-ADHD controls by psychiatric interview and self-administered reports on the Adult ADHD Quality of Life Scale, Weiss Functional Impairment Rating Scale, Family APGAR, and Adult Self Report Inventory-4. The ADHD group was divided into early-onset ADHD (onset

This prognostic study describes the development and validation of an individualized treatment rule for patients with first-episode schizophrenia., Key Points Question Can an individualized treatment rule be developed from administrative data to improve antipsychotic medication selection for patients with first-episode schizophrenia? Findings In this prognostic study of the records of 32 277 Taiwanese patients with first-episode schizophrenia, an individualized treatment rule based on an ensemble machine learning method was developed. Using this rule, which was developed in a 70% training sample, the estimated treatment success rate was 51.7% when the rule was applied to the remaining 30% of patients in the holdout sample, which was significantly higher than the observed 44.5% treatment success rate in the holdout sample. Meaning Results of this study suggest that a clinically useful individualized treatment rule for antipsychotic medication selection could be associated with an increase in the treatment success in first-episode schizophrenia, although a clinical trial and replication of this result with an expanded predictor set would be needed before clinical implementation., Importance Little guidance exists to date on how to select antipsychotic medications for patients with first-episode schizophrenia. Objective To develop a preliminary individualized treatment rule (ITR) for patients with first-episode schizophrenia. Design, Setting, and Participants This prognostic study obtained data from Taiwan's National Health Insurance Research Database on patients with prescribed antipsychotic medications, ambulatory claims, or discharge diagnoses of a schizophrenic disorder between January 1, 2005, and December 31, 2011. An ITR was developed by applying a targeted minimum loss–based ensemble machine learning method to predict treatment success from baseline clinical and demographic data in a 70% training sample. The model was validated in the remaining 30% of the sample. The probability of treatment success was estimated for each medication for each patient under the model. The analysis was conducted between July 16, 2018, and July 15, 2019. Exposures Fifteen different antipsychotic medications. Main Outcomes and Measures Treatment success was defined as not switching medication and not being hospitalized for 12 months. Results Among the 32 277 patients in the analysis, the mean (SD) age was 36.7 (14.3) years, and 15 752 (48.8%) were male. In the validation sample, the treatment success rate (SE) was 51.7% (1.0%) under the ITR and was 44.5% (0.5%) in the observed population (Z = 7.1; P

Objectives: Methylphenidate (MPH) is highly effective in controlling the symptoms of attention-deficit/hyperactivity disorder (ADHD), but some children with ADHD either do not respond to, or do not tolerate, treatment. Dextromethorphan (DM) is a neuroprotective agent which has been used in the treatment of neuropsychiatric disorders. This clinical trial had examined the effect of DM on the use of MPH in the children with ADHD. Methods: This randomized double-blind clinical trial had evaluated 44 male outpatients, aged between 6 and 12 years, with a diagnosis of ADHD. The study subjects were randomly assigned into one of the two groups: receiving MPH alone (15-60 mg per day) or MPH plus DM (30-60 mg per day) for 8 weeks. Assessments, comprising the Chinese version of the Child Behavior Checklist (CBCL-C) scale and the Swanson, Nolan and Pelham Questionnaire (SNAP)-IV rating tests conducted by parents and the serum cytokines measured by microarray and enzyme-linked immunosorband assay (ELISA), were compared between groups at baseline and at 8 weeks after the medication was started. Results: There were a significant decrease at the mean scores of both CBCL-C and SNAP-IV scales after 8 weeks of treatment, but no significant differences between MPH and MPH+DM groups. Compared with the MPH-only group, the mean scores of some psychometric parameters reported on the CBCL-C and SNAP-IV scales regarding time effects as well as the attention problems on the CBCL-C scale regarding group effect were significantly higher in the DM+MPH group. Although there were no significant differences in the levels of various serum cytokines between groups, the subjects in the DM-MPH group had relatively fewer and lower levels of adverse effects. Significant interactions were found between the withdrawn/depression item reported on the CBCL-C scale and tumor necrosis factor α (ခTNF-α) (p = 0.027), as well as between thought problems item on the CBCL-C and TNF-α (p = 0.028) in subjects who had received DM+MPH treatment. Conclusion: Following the trial, DM+MPH was not superior to MPH alone for the treatment of children with ADHD, yet DM may potentially have negative effects on ADHD symptoms when combined with MPH. Clinical Trial Registration: Clinicaltrials.gov, trial number: NCT01787136.

The norepinephrine transporter gene (SLC6A2) and deficits in visual memory and attention were associated with attention-deficit/hyperactivity disorder (ADHD). The present study aimed to examine whether the SLC6A2 rs36011 (T)/rs1566652 (G) haplotype affected the intrinsic brain activity in children with ADHD and whether these gene-brain modulations were associated with visual memory and attention in this population. A total of 96 drug-naive children with ADHD and 114 typically developing children (TDC) were recruited. We analyzed intrinsic brain activity with regional homogeneity (ReHo) and degree centrality (DC). Visual memory and visual attention were assessed by the delayed matching to sample (DMS) and rapid visual information processing (RVIP) tasks, respectively. The SNP genotyping of rs36011 and rs1566652 was performed. Children with ADHD showed lower ReHo and DC in the cuneus and lingual gyri than TDC. The TG haplotype was associated with significantly increased DC in the right precentral and postcentral gyri. Significant interactions of ADHD status and the TG haplotype were found in the right postcentral gyrus and superior parietal lobule for ReHo. For the ADHD-TG group, we found significant correlations of performance on the DMS and RVIP tasks with ReHo in bilateral precentral-postcentral gyri and the right postcentral gyrus-superior parietal lobule and DC in bilateral precentral-postcentral gyri. A novel gene-brain-behavior association was identified in which the intrinsic brain activity of the sensorimotor and dorsal attention networks was related to visual memory and visual attention in ADHD children with the SLC6A2 rs36011 (T)/rs1566652 (G) haplotype.

Objective Although there are frequent reports of shared neurofunctional and neurostructural alterations among probands with attention-deficit/hyperactivity disorder (ADHD) and their unaffected siblings, there is little knowledge regarding whether abnormalities in the resting-state functional connectivity of ADHD probands is also expressed in unaffected siblings, or whether this unaffected (but at-risk) cohort manifests distinct patterns. Method We used a multivariate connectome-wide association study examining intrinsic functional connectivity with resting-state functional magnetic resonance imaging (MRI) in a sample (aged 8−17 years) of medication-naive ADHD probands (n = 56), their unaffected siblings (n = 55), and typically developing (TD) youths (n = 106). Results ADHD probands showed, relative to TD youths, increased connectivity between the default-mode network (DMN) and task-positive networks. Relative to ADHD and TD groups, respectively, unaffected siblings showed increased connectivity within the salience network and reduced connectivity between the DMN and salience network. No shared alterations in functional connectivity among ADHD probands and their unaffected siblings were identified. These findings were largely confirmed by complementary pairwise connectomic comparisons. However, the main connectivity differences between ADHD and unaffected siblings were not replicated in a tightly age- and sex-matched subsample (20 proband−sibling pairs and 60 TD youths). Conclusion Our findings suggest that increased functional segregation related to the attention networks, especially the salience (ventral attention) system, may be a potential feature of at-risk siblings who remain unaffected by ADHD expression. Further replications are needed in other larger and sex-matched samples. Clinical trial registration information: Structural and Functional Connectivity of Frontostriatal and Frontoparietal Networks as Endophenotypes of ADHD; https://clinicaltrials.gov/ ; NCT01682915 .

Sensory symptoms are common in individuals with autism spectrum disorder (ASD). Altered sensory gating may cause sensory overload. However, whether ASD individuals have P50 gating deficits is controversial in childhood and lacks evidence in adulthood. Beyond P50, fewer studies have examined N100 or P200, although N100 is considered to be more reliable than P50. Also, the clinical correlates of these parameters are mostly unknown. This study aimed to investigate P50, N100, and P200 sensory gating in adolescents and young adults with ASD and examine their clinical correlates. In a sample of 34 ASD participants (mean age 20.6 ± 4.1, female 5.9%) and 34 sex- and age-matched typically-developing controls (TDC, mean age 20.4 ± 3.1), we investigated P50, N100, and P200 sensory gating by a paired-click paradigm, which generated the data of S1 amplitude after the first click and S2 amplitude after the second click. We found that compared to TDC, ASD participants had significant N100 suppression deficits reflected by a larger N100 S2 amplitude, smaller N100 ratio of S2 over S1, and the difference between the two amplitudes. N100 S2 amplitude was significantly associated with sensory sensitivity independent of the diagnosis. Although there was no group difference in P50 suppression, S1 amplitude was negatively associated with social deficits in ASD. P200 gating parameters were correlated with attention switching difficulty. Our findings suggest N100 gating deficit in adolescents and young adults with ASD. The relationships between P50 S1 and social deficits and between N100 S2 and sensory sensitivity warrant further investigation.

BackgroundOur 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.MethodsWe 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.ResultsBoth 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.ConclusionIndividuals 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.

Psychiatric comorbidities are common in individuals with attention-deficit/hyperactivity disorder (ADHD). In this study, we sought to evaluate the effects of medication and childhood ADHD subtypes on psychiatric comorbidities among adults with ADHD as compared to healthy adult controls. We assessed 121 drug-naïve adults with ADHD, 93 treated adults with ADHD, and 145 healthy controls (age 18-36 years) using semi-structured psychiatric interviews, intelligence tests, and medical records. Drug-naïve adults with ADHD had more comorbidities than treated adults with ADHD and controls. Childhood ADHD-combined subtype, relative to ADHD-inattentive subtype, was associated with higher risks of comorbidities. Current medication treatment was associate with a higher risk for anxiety disorders, and longer treatment duration was associated with lower risks of mood disorders and sleep disorders. Our results indicate that no medication treatment, short treatment duration, and childhood ADHD-combined subtype are associated with increased risks for psychiatric comorbidities among adults with ADHD.

Inability to carry out cohesive narratives has been identified in children with autism spectrum disorder (ASD). However, deriving cohesion measures is often done using manual labeling or relying on expert-crafted features. In this work, we develop a novel LSTM framework to learn the embedded narrative cohesion representation from data directly. Our lexical coherence representation achieves a promising recognition accuracy of 92% in classifying between typically-developing (TD) and ASD children, as compared to 73% by using conventional coherence measures computed from syntactic, word usage, and latent semantic analysis. We perform additional validity analyses on our proposed representation. By experimentally introducing incoherence in the TD's story-telling narratives through word and sentence-level shuffling, the derived lexical coherence representation from these incoherent TD data samples result in a representation closer to those of ASD data samples.

Objective Existing evidence on long-term psychotropic polypharmacy in older people is scarce despite serious safety concerns regarding this issue. This study aims to identify distinct trajectories of longitudinal psychotropic agent use and to examine the association with the risk of mortality and unplanned hospitalization according to distinct trajectories. Design A retrospective longitudinal cohort study based on data from Taiwan's National Health Insurance Research Database (NHIRD). Setting and participants A population-based study including 39,803 eligible participants aged 65 years or older who were newly prescribed oral psychotropic agents in 2004. Measures We assessed 5 years of monthly consumption of psychotropic agents among eligible participants and used group-based trajectory modeling to identify distinct groups of longitudinal psychotropic use. Cox proportional hazards models were used to examine the association between distinct trajectories of longitudinal psychotropic agent use and subsequent 1- and 3-year unplanned hospitalization and all-cause mortality. Results Among 39,803 eligible participants, we identified 5 trajectories of longitudinal psychotropic agent use over a 5-year follow-up period: sustained intense (7.1%), moderate increasing (12.1%), decreasing (13.4%), slowly increasing (15.7%), and infrequent users (51.6%). Moderate increasing and sustained intense use were associated with significantly higher risks of unplanned hospitalization [moderate increasing use: hazard ratio [HR] 1.30, 95% confidence interval (CI) 1.18-1.44; sustained intense use: HR 1.40, 95% CI 1.24-1.58] and all-cause mortality (moderate increasing use: HR 1.25, 95% CI 1.09-1.44; sustained intense use: HR 1.32, 95% CI 1.12-1.56) than infrequent use. Similar results were observed at 3 years of follow-up. Conclusions/Implications Older people with moderately increasing and sustained intense use of psychotropic agents over time had higher risks of unplanned hospitalization and mortality. Tracking older people's use of psychotropic agents over time may help to identify individuals at greatest risk of unplanned hospitalization and mortality.

We compared the maternal reports on mothering and family processes between 160 youth with autism spectrum disorder (ASD) and 160 age and gender-matched typically developing (TD) youth stratified by personal characteristics from Taiwan. The ASD groups consisted of 51 'typical autism' (TA), 52 'high-functioning autism' (HFA), and 57 'Asperger syndrome (AS).' Maternal reports showed that youth with ASD obtained less affection and more protection from the mother, and had less active mother-child interactions and more behavioral problems at home. Their mothers perceived less family support when compared to mothers of TD youth. Moreover, both TA and AS groups had more maternal protection and less maternal perceived family support, whereas HFA and co-occurring ADHD were only associated with more behavioral problems at home. The maternal and family process may vary across different ASD subgroups.

Background Impaired social interaction is one of the essential features of autism spectrum disorder (ASD). Our previous copy number variation (CNV) study discovered a novel deleted region associated with ASD. One of the genes included in the deleted region is ARHGEF10. A missense mutation of ARHGEF10 has been reported to be one of the contributing factors in several diseases of the central nervous system. However, the relationship between the loss of ARHGEF10 and the clinical symptoms of ASD is unclear. Methods We generated Arhgef10 knockout mice as a model of ASD and characterized the social behavior and the biochemical changes in the brains of the knockout mice. Results Compared with their wild-type littermates, the Arhgef10-depleted mice showed social interaction impairment, hyperactivity, and decreased depression-like and anxiety-like behavior. Behavioral measures of learning in the Morris water maze were not affected by Arhgef10 deficiency. Moreover, neurotransmitters including serotonin, norepinephrine, and dopamine were significantly increased in different brain regions of the Arhgef10 knockout mice. In addition, monoamine oxidase A (MAO-A) decreased in several brain regions. Conclusions These results suggest that ARHGEF10 is a candidate risk gene for ASD and that the Arhgef10 knockout model could be a tool for studying the mechanisms of neurotransmission in ASD. Trial registration Animal studies were approved by the Institutional Animal Care and Use Committee of National Taiwan University (IACUC 20150023). Registered 1 August 2015. Electronic supplementary material The online version of this article (10.1186/s13229-018-0197-5) contains supplementary material, which is available to authorized users.

Attention-deficit/hyperactivity disorder (ADHD) is associated with significant impairments in social, educational, and occupational functioning, as well as specific strengths. Currently, there is no internationally accepted standard to assess the functioning of individuals with ADHD. WHO’s International Classification of Functioning, Disability and Health—child and youth version (ICF) can serve as a conceptual basis for such a standard. The objective of this study is to develop a comprehensive, a common brief, and three age-appropriate brief ICF Core Sets for ADHD. Using a standardised methodology, four international preparatory studies generated 132 second-level ICF candidate categories that served as the basis for developing ADHD Core Sets. Using these categories and following an iterative consensus process, 20 ADHD experts from nine professional disciplines and representing all six WHO regions selected the most relevant categories to constitute the ADHD Core Sets. The consensus process resulted in 72 second-level ICF categories forming the comprehensive ICF Core Set—these represented 8 body functions, 35 activities and participation, and 29 environmental categories. A Common Brief Core Set that included 38 categories was also defined. Age-specific brief Core Sets included a 47 category preschool version for 0–5 years old, a 55 category school-age version for 6–16 years old, and a 52 category version for older adolescents and adults 17 years old and above. The ICF Core Sets for ADHD mark a milestone toward an internationally standardised functional assessment of ADHD across the lifespan, and across educational, administrative, clinical, and research settings. © 2018 The Author(s)

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder, and the exact causal mechanism is unknown. Dysregulated allele-specific expression (ASE) has been identified in persons with ASD; however, a comprehensive analysis of ASE has not been conducted in a family quartet with ASD. To fill this gap, we analyzed ASE using genomic DNA from parent and offspring and RNA from offspring’s postmortem prefrontal cortex (PFC); one of the two offspring had been diagnosed with ASD. DNA- and RNA-sequencing revealed distinct ASE patterns from the PFC of both offspring. However, only the PFC of the offspring with ASD exhibited a mono-to-biallelic switch for LRP2BP and ZNF407. We also identified a novel site of RNA-editing in KMT2C in addition to new monoallelically-expressed genes and miRNAs. Our results demonstrate the prevalence of ASE in human PFC and ASE abnormalities in the PFC of a person with ASD. Taken together, these findings may provide mechanistic insights into the pathogenesis of ASD.

Visual system development is light-experience dependent, which strongly implicates epigenetic mechanisms in light-regulated maturation. Among many epigenetic processes, genomic imprinting is an epigenetic mechanism through which monoallelic gene expression occurs in a parent-of-origin-specific manner. It is unknown if genomic imprinting contributes to visual system development. We profiled the transcriptome and imprintome during critical periods of mouse visual system development under normal- and dark-rearing conditions using B6/CAST F1 hybrid mice. We identified experience-regulated, isoform-specific and brain-region-specific imprinted genes. We also found imprinted microRNAs were predominantly clustered into the Dlk1-Dio3 imprinted locus with light experience affecting some imprinted miRNA expression. Our findings provide the first comprehensive analysis of light-experience regulation of the transcriptome and imprintome during critical periods of visual system development. Our results may contribute to therapeutic strategies for visual impairments and circadian rhythm disorders resulting from a dysfunctional imprintome.

BackgroundThe long-term outcome of patients with both diabetes and schizophrenia remains unclear.AimsTo explore whether having schizophrenia increases the risk of advanced complications and mortality in people with diabetes.MethodThis 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.ResultsThe 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.ConclusionsPatients 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.

Objective: We evaluated the psychiatric comorbidities in adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder as a function of recalled symptom onset before and after the age of 7 years and whether the childhood attention-deficit/hyperactivity disorder symptoms were associated with psychiatric comorbidities. Method: In all, 214 adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder and 174 non-attention-deficit/hyperactivity disorder controls (aged 17–40 years) received psychiatric interviews to confirm their previous and current attention-deficit/hyperactivity disorder status and other psychiatric diagnoses. Demographics and risks of lifetime psychiatric disorders were compared among three groups: (1) attention-deficit/hyperactivity disorder, onset Results: Regardless of the age of onset, attention-deficit/hyperactivity disorder was significantly associated with a wide range of psychiatric comorbidities. There were similar comorbid patterns between early- and late-onset attention-deficit/hyperactivity disorder. Regardless of attention-deficit/hyperactivity disorder diagnosis, increased severity of attention-deficit/hyperactivity disorder symptoms was associated with higher risks of oppositional defiant disorder, conduct disorder, dysthymia and sleep disorder but not major depression, which was associated with the attention-deficit/hyperactivity disorder diagnosis. Conclusion: Our findings suggest that elevating the threshold of age of onset to 12 years in Diagnostic and Statistical Manual of Mental disorders, 5th edition would not over-diagnose attention-deficit/hyperactivity disorder in the adult population. Recalled childhood attention-deficit/hyperactivity disorder symptom severity was correlated with conduct disorder, oppositional defiant disorder, dysthymia and sleep disorders.

To investigate the efficacy of the "Life Adaptation Skills Training (LAST)" program for persons with depression.Sixty-eight subjects with depressive disorder were recruited from psychiatric outpatient clinics in Taipei city and were randomly assigned to either an intervention group (N=33), or a control group (N=35). The intervention group received 24-sessions of the LAST program, as well as phone contact mainly related to support for a total of 24 times. The control group only received phone contact 24 times. The primary outcome measure utilized was the World Health Organization Quality of Life-BREF-Taiwan version. Secondary outcome measures included the Occupational self-assessment, the Mastery scale, the Social support questionnaire, the Beck anxiety inventory, the Beck depression inventory-II, and the Beck scale for suicide ideation. The mixed-effects linear model was applied to analyze the incremental efficacy of the LAST program, and the partial eta squared (ηp(2)) was used to examine the within- and between- group effect size.The subjects who participated in the LAST program showed significant incremental improvements with moderate to large between-group effect sizes on their level of anxiety (-5.45±2.34, p0.05; ηp(2)=0.083) and level of suicidal ideation (-3.09±1.11, p0.01; ηp(2)=0.157) when compared to the control group. The reduction of suicidal ideations had a maintenance effect for three months after the end of intervention (-3.44±1.09, p0.01), with moderate between-group effect sizes (ηp(2)=0.101). Both groups showed significant improvement on overall QOL, overall health, physical QOL, psychological QOL, level of anxiety, and level of depression. The within-group effect sizes achieved large effects in the intervention group (ηp(2)=0.328-0.544), and were larger than that of the control group.A small sample size in the study, a high dropout rate, lower compliance rates for the intervention group, and lacking of true control group.The occupation-based LAST program, which focuses on lifestyle rearrangement and coping skills enhancement, could significantly improve the level of anxiety and suicidal ideations for persons with depression.

BACKGROUND: The neural substrate for clinical symptoms and neuropsychological performance in individuals with attention-deficit/hyperactivity disorder (ADHD) has rarely been studied and has yielded inconsistent results. We sought to compare the microstructural property of fibre tracts associated with the prefrontal cortex and its association with ADHD symptoms and a wide range of attention performance in youth with ADHD and healthy controls. METHODS: We assessed youths with ADHD and age-, sex-, handedness-, coil- and intelligence-matched controls using the Conners' Continuous Performance Test (CCPT) for attention performance and MRI. The 10 target tracts, including the bilateral frontostriatal tracts (caudate to dorsolateral prefrontal cortex, ventrolateral prefrontal cortex and orbitofrontal cortex), superior longitudinal fasciculus (SLF) and cingulum bundle were reconstructed using diffusion spectrum imaging tractography. We computed generalized fractional anisotropy (GFA) values to indicate tract-specific microstructural property. RESULTS: We included 50 youths with ADHD and 50 healthy controls in our study. Youths with ADHD had lower GFA in the left frontostriatal tracts, bilateral SLF and right cingulum bundle and performed worse in the CCPT than controls. Furthermore, alteration of the right SLF GFA was most significantly associated with the clinical symptom of inattention in youths with ADHD. Finally, youths with ADHD had differential association patterns of the 10 fibre tract GFA values with attention performance compared with controls. LIMITATIONS: Ten of the youths with ADHD were treated with methylphenidate, which may have long-term effects on microstructural property. CONCLUSION: Our study highlights the importance of the SLF, cingulum bundle and frontostriatal tracts for clinical symptoms and attention performance in youths with ADHD and demonstrates the involvement of different fibre tracts in attention performance in these individuals. Language: en

The efficacy of both methylphenidate and atomoxetine has been established in placebo-controlled trials. The present study aimed to directly compare the efficacy of methylphenidate and atomoxetine in improving symptoms among children with attention-deficit/hyperactivity disorder (ADHD).The study sample included 160 drug-naïve children and adolescents 7-16 years of age, with DSM-IV-defined ADHD, randomly assigned to osmotic-release oral system methylphenidate (OROS-methylphenidate) (n=80) and atomoxetine (n=80) in a 24 week, open-label, head-to-head clinical trial. The primary efficacy measure was the score of the ADHD Rating Scale-IV Parents Version: Investigator Administered and Scored (ADHD-RS-IV). The secondary efficacy measures included the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) and Chinese Swanson, Nolan, and Pelham IV scale (SNAP-IV), based on the ratings of investigators, parents, teachers, and subjects.At week 24, mean changes in ADHD-RS-IV Inattention scores were 13.58 points (Cohen's d, -3.08) for OROS-methylphenidate and 12.65 points (Cohen's d, -3.05) for atomoxetine; and mean changes in ADHD-RS-IV Hyperactivity-Impulsivity scores were 10.16 points (Cohen's d, -1.75) for OROS-methylphenidate and 10.68 points (Cohen's d, -1.87) for atomoxetine. In terms of parent-, teacher-, and self-ratings on behavioral symptoms, both of the two treatment groups significantly decreased on the SNAP-IV scores at the end-point, with effect sizes ranging from 0.9 to 0.96 on the Inattention subscale and from 0.61 to 0.8 on the Hyperactivity/Impulsivity subscale for OROS-methylphenidate; and from 0.51 to 0.88 on the Inattention subscale and from 0.29 to 0.57 on the Hyperactivity/Impulsivity subscale for atomoxetine. No statistically significant differences between treatment groups were observed on the outcome measures. Vomiting, somnolence, and dizziness were reported more often for atomoxetine than for OROS-methylphenidate, whereas insomnia was reported more often for OROS-methylphenidate than for atomoxetine.After 24 weeks of treatment, OROS-methylphenidate and atomoxetine had comparable efficacy in reducing core ADHD symptoms in drug-naïve children and adolescents with ADHD.

Autism spectrum disorder is a heterogeneous neurodevelopmental disorder with strong genetic basis. To identify common genetic variations conferring the risk of ASD, we performed a two-stage genome-wide association study using ASD family and healthy control samples obtained from East Asian populations. A total of 166 ASD families (n = 500) and 642 healthy controls from the Japanese population were used as the discovery cohort. Approximately 900,000 single nucleotide polymorphisms (SNPs) were genotyped using Affymetrix Genome-Wide Human SNP array 6.0 chips. In the replication stage, 205 Japanese ASD cases and 184 healthy controls, as well as 418 Chinese Han trios (n = 1,254), were genotyped by TaqMan platform. Case-control analysis, family based association test, and transmission/disequilibrium test (TDT) were then conducted to test the association. In the discovery stage, significant associations were suggested for 14 loci, including 5 known ASD candidate genes: GPC6, JARID2, YTHDC2, CNTN4, and CSMD1. In addition, significant associations were identified for several novel genes with intriguing functions, such as JPH3, PTPRD, CUX1, and RIT2. After a meta-analysis combining the Japanese replication samples, the strongest signal was found at rs16976358 (P = 6.04 × 10(-7)), which is located near the RIT2 gene. In summary, our results provide independent support to known ASD candidate genes and highlight a number of novel genes warranted to be further investigated in a larger sample set in an effort to improve our understanding of the genetic basis of ASD.

BACKGROUND: Individuals with autism spectrum disorder (ASD) experience long-term social impairment and their comorbid psychiatric conditions negatively impact adaptive functioning. The aims of the study are to investigate whether comorbid psychopathologies, such as anxiety/depression, inattention, hyperactivity/impulsivity, and oppositional behaviors, mediated the link between autistic symptoms and social maladjustment. METHOD: One hundred and twenty-four youths diagnosed with a clinical diagnosis of DSM-IV ASD (mean age, 10.6 ± 3.3 years) participated in this longitudinal study. They were assessed using semistructured diagnostic interviews on ASD and other psychiatric conditions at recruitment. Follow-up interviews took place approximately 3 years later (37.59 ± 15 months) while the parents reported to the Social Adjustment Inventory for Children and Adolescents on their children's social adjustment. Mediation models were used to examine the mediating effect of comorbid psychopathologies on social adjustment. RESULTS: Youths with ASD had worse school, peer, and home functions than controls at follow-up assessment. In general, comorbid psychiatric conditions mediated the link between autistic symptoms and different domains of social adjustment, independent of age, sex, and full-scale IQ. Additionally, we found specific mediating effects of anxiety/depression and inattention on school functions; anxiety/depression on peer relationships; and oppositional behaviors on home behaviors. CONCLUSION: Early comorbid psychopathologies may further impair later social adjustment in youths with ASD and an early identification and intervention of these comorbid conditions are suggested. Language: en

This longitudinal study investigated the prevalence, predictors, and related factors for Internet addiction among elementary and junior high school students in Taiwan. A convenient sample of grades 3, 5, and 8 students (n = 1153) was recruited from six elementary and one junior high schools. They were assessed during the beginning and the end of the spring semester of 2013. Internet addiction was examined by the Chen Internet Addiction Scale (CIAS). Other factors were screened using the Chinese version of the Autism Spectrum Quotient (AQ) for autistic trait, the Parental Bonding Instrument (PBI) for parenting, the Family APGAR for family support, the Social Adjustment Inventory for Children and Adolescents for social function, and the Swanson, Nolan, and Pelham, version IV scale (SNAP-IV) for ADHD symptoms. The prevalence of Internet addiction decreased from 11.4% to 10.6%. Male, low family support, poor social adjustment, and high ADHD-related symptoms were related to Internet addiction. However, there was an inverse relationship between autistic traits and Internet addiction. Further, its predictivity could be accounted by poor academic performance, male, and protective parenting style. Internet addiction is not uncommon among youths in Taiwan. The predictors identified in this study could be the specific measures for the development of a prevention program for Internet addiction in the youth population.

The frontoparietal control network, anatomically and functionally interposed between the dorsal attention network and default mode network, underpins executive control functions. Individuals with attention-deficit/hyperactivity disorder (ADHD) commonly exhibit deficits in executive functions, which are mainly mediated by the frontoparietal control network. Involvement of the frontoparietal control network based on the anterior prefrontal cortex in neurobiological mechanisms of ADHD has yet to be tested. We used resting-state functional MRI and seed-based correlation analyses to investigate functional connectivity of the frontoparietal control network in a sample of 25 children with ADHD (7–14 years; mean 9.94±1.77 years; 20 males), and 25 age-, sex-, and performance IQ-matched typically developing (TD) children. All participants had limited in-scanner head motion. Spearman’s rank correlations were used to test the associations between altered patterns of functional connectivity with clinical symptoms and executive functions, measured by the Conners’ Continuous Performance Test and Spatial Span in the Cambridge Neuropsychological Test Automated Battery. Compared with TD children, children with ADHD demonstrated weaker connectivity between the right anterior prefrontal cortex (PFC) and the right ventrolateral PFC, and between the left anterior PFC and the right inferior parietal lobule. Furthermore, this aberrant connectivity of the frontoparietal control network in ADHD was associated with symptoms of impulsivity and opposition-defiance, as well as impaired response inhibition and attentional control. The findings support potential integration of the disconnection model and the executive dysfunction model for ADHD. Atypical frontoparietal control network may play a pivotal role in the pathophysiology of ADHD. (JINS, 2015, 21, 271–284)

Previous studies using neural activity recording and neuroimaging techniques have reported functional deficits in the mirror neuron system (MNS) for individuals with autism spectrum disorder (ASD). However, a few studies focusing on gray and white matter structures of the MNS have yielded inconsistent results. The current study recruited adolescents and young adults with ASD (aged 15-26 years) and age-matched typically developing (TD) controls (aged 14-25 years). The cortical thickness (CT) and microstructural integrity of the tracts connecting the regions forming the classical MNS were investigated. High-resolution T1-weighted imaging and diffusion spectrum imaging were performed to quantify the CT and tract integrity, respectively. The structural covariance of the CT of the MNS regions revealed a weaker coordination of the MNS network in ASD. A strong correlation was found between the integrity of the right frontoparietal tracts and the social communication subscores measured by the Chinese version of the Social Communication Questionnaire. The results showed that there were no significant mean differences in the CTs and tract integrity between the ASD and TD groups, but revealed a moderate or even reverse age effect on the frontal MNS structures in ASD. In conclusion, aberrant structural coordination may be an underlying factor affecting the function of the MNS in ASD patients. The association between the right frontoparietal tracts and social communication performance implies a neural correlate of communication processing in the autistic brain. This study provides evidence of abnormal MNS structures and their influence on social communication in individuals with ASD.

The extent to which parenting styles can influence secondary psychiatric symptoms among young adults with ADHD symptoms is unknown. This issue was investigated in a sample of 2284 incoming college students (male, 50.6%), who completed standardized questionnaires about adult ADHD symptoms, other DSM-IV symptoms, and their parents' parenting styles before their ages of 16. Among them, 2.8% and 22.8% were classified as having ADHD symptoms and sub-threshold ADHD symptoms, respectively. Logistic regression was used to compare the comorbid rates of psychiatric symptoms among the ADHD, sub-threshold ADHD and non-ADHD groups while multiple linear regressions were used to examine the moderating role of gender and parenting styles over the associations between ADHD and other psychiatric symptoms. Both ADHD groups were significantly more likely than other incoming students to have other DSM-IV symptoms. Parental care was negatively associated and parental overprotection/control positively associated with these psychiatric symptoms. Furthermore, significant interactions were found of parenting style with both threshold and sub-threshold ADHD in predicting wide-ranging comorbid symptoms. Specifically, the associations of ADHD with some externalizing symptoms were inversely related to level of paternal care, while associations of ADHD and sub-threshold ADHD with wide-ranging comorbid symptoms were positively related to level of maternal and paternal overprotection/control. These results suggest that parenting styles may modify the effects of ADHD on the risk of a wide range of temporally secondary DSM-IV symptoms among incoming college students, although other causal dynamics might be at work that need to be investigated in longitudinal studies.

The posterior right temporo-parietal junction (pRTPJ) is a key brain region representing other's mental status. Despite reports of atypical activation at pRTPJ during mentalizing in individuals with autism spectrum disorder (ASD), the intrinsic functional connectivity (iFC) of the pRTPJ remains under-investigated. We examined whether boys with ASD show altered resting-state iFC of the pRTPJ, and whether atypical iFC of the pRTPJ is associated with social deficits in ASD in a sample of 40 boys with high-functioning ASD (aged 9–17 years, mean age, 12.38 ± 2.17; mean IQ, 105.60 ± 16.06) and 42 typically developing (TD) boys (aged 9–17 years, mean age, 11.64 ± 2.71; mean IQ, 111.29 ± 13.45). Both groups received resting-state fMRI assessment after imaging data quality control for in-scanner head motion and spatial coverage. Seed-based approach was used to investigate iFC of the pRTPJ. TD and ASD boys demonstrated a resting-state pRTPJ iFC pattern comparable to the known spatial involvement of the default-mode network. Boys with ASD showed pRTPJ hyperconnectivity relative to TD boys in the right ventral occipito-temporal cortex. This atypically increased iFC in the ASD group was positively correlated with social deficits assessed by the Chinese version of the Autism Diagnostic Interview-Revised and the Social Responsive Scale. Our findings provide empirical support for functional “dysconnectivity,” that is, atypical functional integration among brain regions, as an integral component of the atypical neurobiology of ASD. Autism Res 2015, 8: 427–441. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Prenatal cell‐free DNA (cfDNA) testing, or non‐invasive prenatal testing, has been shown to be capable of detecting certain microdeletion syndromes1 and has recently been extended to genome‐wide detection of subchromosomal abnormalities, including microduplications2. Here we describe a fetus with multiple structural anomalies that was diagnosed with double segmental duplications by cfDNA testing at our laboratory (Department of Genomic Medicine, Changhua Christian Hospital, Taiwan). We confirmed the cfDNA test result by chromosomal microarray (CMA) and karyotyping, and ascertained that the fetus had an unbalanced translocation inherited from a parental carrier of a balanced translocation involving t(11;22)(q23;q11.2).

Deficits in inhibitory control and visual processing are common in youths with attention-deficit/hyperactivity disorder (ADHD), but little is known about endophenotypes for unaffected siblings of youths with ADHD. This study aimed to investigate the potential endophenotypes of brain activation and performance in inhibitory control and visual processing among ADHD probands, their unaffected siblings, and neurotypical youths. We assessed 27 ADHD probands, 27 unaffected siblings, and 27 age-, gender-, and IQ-matched neurotypical youths using the counting Stroop functional magnetic resonance imaging and two tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB): rapid visual information processing (RVP) for inhibitory control and spatial span (SSP) for visual processing. ADHD probands showed greater activation than their unaffected siblings and neurotypical youths in the right inferior frontal gyrus (IFG) and anterior cingulate cortex. Increased activation in the right IFG was positively correlated with the mean latency of the RVP in ADHD probands. Moreover, ADHD probands and their unaffected siblings showed less activation in the left superior parietal lobule (SPL) than neurotypical youths. Increased activation in the left SPL was positively correlated with the spatial length of the SSP in neurotypical youths. Our findings suggest that less activation in the left SPL might be considered as a candidate imaging endophenotype for visual processing in ADHD.

Although recent studies revealed impaired self-regulation (dysregulation) in autism spectrum disorder (ASD), neural correlates of dysregulation and its impacts on autistic neuroanatomy remain unclear. Voxel-based morphometry was applied on structural MRI images in 81 ASD and 61 typically developing (TD) boys aged 7-17years. Dysregulation was defined by the sum of T-scores of Attention, Aggression, and Anxiety/Depression subscales in the Child Behavior Checklist>180. There were 53 and 28 boys in the ASD+Dysregulation and ASD-Dysregulation groups, respectively. First, we compared regional gray matter (GM) volume for ASD and TD. Second, we investigated regional GM volumetric differences among the ASD+Dysregulation, ASD-Dysregulation and TD groups. Lastly, shared and distinct neurostructural correlates of dysregulation were investigated in the ASD and TD groups. The ASD-TD difference on neuroanatomy no longer existed after controlling the dysregulation severity. ASD+Dysregulation had larger regional GM volumes in the right fusiform gyrus, and smaller GM volumes in the anterior prefrontal cortex than ASD-Dysregulation and TD, respectively. ASD+Dysregulation had smaller GM volumes in the left lateral occipital/superior parietal cortex than TD boys. No GM difference was identified between ASD-Dysregulation and TD. ASD and TD had a shared association between GM volumes in the orbitofrontal cortex and dysregulation levels. Our findings suggest that atypical neuroanatomy associated with ASD might partially reflect a disproportionate level of impaired self-regulation. Categorical and dimensional considerations of dysregulation should be implemented in future ASD studies.

Studies have shown that Tai Chi Chuan (TCC) training has benefits on task-switching ability. However, the neural correlates underlying the effects of TCC training on task-switching ability remain unclear. Using task-related functional magnetic resonance imaging (fMRI) with a numerical Stroop paradigm, we investigated changes of prefrontal brain activation and behavioral performance during task-switching before and after TCC training and examined the relationships between changes in brain activation and task-switching behavioral performance. Cognitively normal older adults were randomly assigned to either the TCC or control (CON) group. Over a 12-week period, the TCC group received three 60-min sessions of Yang-style TCC training weekly, whereas the CON group only received one telephone consultation biweekly and did not alter their life style. All participants underwent assessments of physical functions and neuropsychological functions of task-switching, and fMRI scans, before and after the intervention. Twenty-six (TCC, N = 16; CON, N = 10) participants completed the entire experimental procedure. We found significant group by time interaction effects on behavioral and brain activation measures. Specifically, the TCC group showed improved physical function, decreased errors on task-switching performance, and increased left superior frontal activation for Switch > Non-switch contrast from pre- to post-intervention, that were not seen in the CON group. Intriguingly, TCC participants with greater prefrontal activation increases in the switch condition from pre- to post-intervention presented greater reductions in task-switching errors. These findings suggest that TCC training could potentially provide benefits to some, although not all, older adults to enhance the function of their prefrontal activations during task-switching.

Background The presence of attention-deficit/hyperactive disorder (ADHD) symptoms and impaired attention performance are commonly noted in individuals with autism spectrum disorder (ASD). However, little is known about attention performance in their unaffected siblings. This study aimed to investigate the ADHD-related traits and attention performance in unaffected siblings of probands with autism and Asperger syndrome (AS), as well as the clinical correlates of ADHD-related traits. Methods We assessed the intention, hyperactivity-impulsivity, and oppositional symptoms, and attention profiles of 199 probands with a diagnosis of ASD (122 autism, 77 AS), their unaffected siblings, and 196 typically developing controls (TD) by their parents’ reports on the ADHD-related symptoms and the Connors' Continuous Performance Test (CCPT), respectively. Results Compared to TD, unaffected siblings of ASD probands were more hyperactive/impulsive and oppositional, particularly unaffected siblings of AS probands. In CCPT, unaffected siblings of AS have intermediate levels of performance between probands with AS and TD on focused attention and sustained attention but were not statistically different from AS probands or TD in these attention profiles. In contrast, unaffected siblings of autism probands have significantly better CCPT performance when compared to autism probands but not to TD. In addition, stereotyped behaviors predicted ADHD-related traits in both sibling groups, but distinctive patterns of other correlates for ADHD-related traits were found between the two sibling groups. Conclusions This work suggested that unaffected siblings of AS, but not autism, have more hyperactive/impulsive traits and a trend of pervasive attention deficits assessed by CCPT which might serve as potential endophenotypes for genetic studies in AS. Trial registration ClinicalTrials.gov, NCT01582256 Electronic supplementary material The online version of this article (doi:10.1186/s13229-017-0153-9) contains supplementary material, which is available to authorized users.

Background Several longitudinal studies have shown the partial symptomatic persistence of attention-deficit hyperactivity disorder (ADHD) in clinic-based samples. However, little is known about the patterns and trajectories of ADHD symptoms in community-based populations. Methods To differentiate developmental trajectories of ADHD symptoms over 1 year, with a four-wave quarterly follow-up in children and adolescents in the community of Taiwan, we conducted this prospective study in 1281 students in grade 3, 5, and 8. All the students in the regular classes rather than special educational classes were eligible and recruited to the study. Inattention, hyperactivity–impulsivity, and opposition-defiance were rated by parent reports on the Chinese version of the Swanson, Nolan, and Pelham Version IV Scale (SNAP-IV). Group-based trajectory modeling and multivariable regression analyses were used to explore the individual, family and social factors associated with differential trajectories. Results Trajectories were classified as Low (29.9–40.6%), Intermediate (52.5–58.5%) and High (6.9–12.5%) based on the symptom severity of ADHD symptoms assessed by the SNAP-IV. The proportion of children in the high ADHD trajectory might approximately reflect the prevalence of ADHD in Taiwan. The following factors differentiated High from Low trajectories: male gender, more externalizing problems, fewer prosocial behaviors, school dysfunction, more home behavioral problems, and less perceived family support. Conclusions Our findings that the concurrent conditions of emotional or externalizing problems, as well as impaired school and home function at baseline, might differentiate the high ADHD symptoms trajectory from others could help developing the specific measures for managing high ADHD symptoms over time in a school setting. Electronic supplementary material The online version of this article (doi:10.1186/s13034-017-0165-4) contains supplementary material, which is available to authorized users.

The majority of studies on parent-child discrepancies in the assessment of adolescent emotional and behavioral problems have been conducted in Western countries. It is believed that parent-adolescent agreement would be higher in societies with a strong culture of familism. We examined whether parent-adolescent discrepancies in the rating of adolescent emotional and behavioral problems are related to parental and family factors in Taiwan. Participants included 1,421 child-parent pairs of 7th-grade students from 12 middle schools in Northern Taiwan and their parents. We calculated Pearson's correlation coefficients to assess the relationship between parental (Child Behavior Checklist, CBCL) and adolescent (Youth Self Report, YSR) report of emotional/behavioral problem syndromes. Regression models were used to assess parent-adolescent differences in relation to parental psychopathology and family factors. We found that parent-adolescent agreement was moderate (r = 0.37). Adolescents reported higher symptom scores than their parents (Mean Total Problem Score: CBCL: 20.79, YSR: 33.14). Parental psychopathology was related to higher parental ratings and better informant agreement. Parents with higher socioeconomic status (SES) tended to report lower scores for adolescent problem syndromes, resulting in higher levels of disagreement. Greater maternal care was related to higher parent-adolescent agreement. Based on our study findings, we conclude that familism values do not seem to improve parent-child agreement in the assessment of adolescent problem syndromes. The finding that higher SES was related to increased discrepancies speaks to the need to explore the culture-specific mechanisms giving rise to informant discrepancies.

Childhood attention-deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder/conduct disorder (ODD/CD) are associated with negative school outcomes. The study aimed to examine the impact of ADHD and ODD/CD on various school functions. 395 youths with ADHD (244 with ADHD + ODD/CD and 151 with ADHD only) and 156 controls received semi-structured psychiatric interviews. School functions were assessed and compared between each group with a multiple-level model. The results showed that youths with ADHD had poorer performance across different domains of school functioning. Youths with ADHD + ODD/CD had more behavioral problems but similar academic performance than those with ADHD only. The multiple linear regression models revealed that ADHD impaired academic performance while ODD/CD aggravated behavioral problems. Our findings imply that comorbid ODD/CD may specifically contribute to social difficulties in youths with ADHD. Measures of early detection and intervention for ODD/CD should be conducted to prevent adverse outcomes.