Miao-Chun Chou

Psychometric properties of the Chinese version of the Autism Spectrum Quotient (AQ)

The Autism Spectrum Quotient (AQ) has been widely used for measuring autistic characteristics in parents of children with autism spectrum disorders (ASD). Nonetheless, its psychometric validity is yet to be justified. This study tested the factor structure of the AQ by means of principal component analysis and confirmatory factor analysis using, for the first time, data from 4192 Taiwanese parents (1208 with ASD children and 2984 with typically developing children). Results yielded a 35-item, 5-dimensional factor solution that had favorable psychometric characteristics (RMSEA = .054; NNFI = .962; CFI = .969) than any of the previously-published AQ factor solutions. Subscales of this new AQ-Chinese model were statistically and semantically coherent, namely: Socialness, Mindreading, Patterns, Attention to Details and Attention Switching. The psychometric properties of the AQ-Chinese did not change between clinic-based and community-based data suggesting good fitting for a continuum of autistic expression. Furthermore, the considerable overlap between the AQ-Chinese and the AQ factor structures derived previously using student samples indicated consistency in the manifestation of the autistic profile across different cultures and age groups. Group differences in the AQ-Chinese scores were in line with previous studies, i.e. males generally scored radically higher than females except in Attention to Details. Interestingly, mothers of ASD children reported lower total AQ scores than community mothers yet no significant group difference for the fathers. Important research and clinical implications pertinent to parents with children with ASD and the utility of the AQ were drawn.

Better efficacy for the osmotic release oral system methylphenidate among poor adherents to immediate‐release methylphenidate in the three ADHD subtypes

Aims:  To determine factors for switching to osmotic release oral system methylphenidate (OROS‐MPH) among poor adherents to immediate‐release methylphenidate (IR‐MPH); and to compare the efficacy of OROS‐MPH on the three attention‐deficit/hyperactivity disorder (ADHD) subtypes in a multi‐site prospective observational study in Taiwan.

Chromosomal abnormalities in patients with autism spectrum disorders from Taiwan.

Autism spectrum disorders (ASD) are childhood‐onset neurodevelopmental disorders characterized by verbal communication impairments, social reciprocity deficits, and the presence of restricted interests and stereotyped behaviors. Genetic factors contribute to the incidence of ASD evidently. However, the genetic spectrum of ASD is highly heterogeneous. Chromosomal abnormalities contribute significantly to the genetic deficits of syndromic and non‐syndromic ASD. In this study, we conducted karyotyping analysis in a sample of 500 patients (447 males, 53 females) with ASD from Taiwan, the largest cohort in Asia, to the best of our knowledge. We found three patients having sex chromosome aneuploidy, including two cases of 47, XXY and one case of 47, XYY. In addition, we detected a novel reciprocal chromosomal translocation between long arms of chromosomes 4 and 14, designated t(4;14)(q31.3;q24.1), in a patient with Aspergers disorder. This translocation was inherited from his unaffected father, suggesting it might not be pathogenic or it needs further hits to become pathogenic. In line with other studies, our study revealed that subjects with sex chromosomal aneuploidy are liable to neurodevelopmental disorders, including ASD, and conventional karyotyping analysis is still a useful tool in detecting chromosomal translocation in patients with ASD, given that array‐based comparative genomic hybridization technology can provide better resolution in detecting copy number variations of genomic DNA.

Remission in Children and Adolescents Diagnosed with Attention-Deficit/Hyperactivity Disorder via an Effective and Tolerable Titration Scheme for Osmotic Release Oral System Methylphenidate

OBJECTIVES The purpose of this study was to identify the optimal dose of osmotic release oral system methylphenidate (OROS-MPH) using a dosage forced-titration scheme to achieve symptomatic remission in children with attention- deficit/hyperactivity disorder (ADHD). We also evaluated the efficacy and safety of, and patient and parent satisfaction with, the change in therapy from immediate-release methylphenidate (IR-MPH) to OROS-MPH over 10 weeks. METHOD We recruited 521 children and adolescents aged 6-18 years with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) diagnosis of ADHD, who had received IR-MPH treatments (<70 mg/day) for at least 1 month. The treatment, switched from IR-MPH to OROS-MPH according to a conversion scheme, started with a 6-week forced-titration phase of OROS-MPH to achieve symptomatic remission (defined as a score of 0 or 1 for each of the first 18 ADHD items in the Chinese version of the Swanson, Nolan, and Pelham, Version IV [SNAP-IV]), followed by a 4-week maintenance phase. The global ADHD severity and drug side effects of the participants were evaluated. Parents completed the ratings scales for the ADHD-related symptoms. Patient and parent satisfaction for the OROS-MPH treatment was also assessed. RESULTS Among the 439 participants with ADHD who completed the trial, 290 participants (66.1%) achieved symptomatic remission. The mean dose of OROS-MPH among participants in remission was 36.7 mg (1.08 mg/kg) per day. Increased efficacy, superior satisfaction, and safety equivalent to that of IR-MPH were demonstrated in intra-individual comparisons from the baseline to the end of study. Determinants for remission included less severe ADHD symptoms (SNAP-IV score < 40), no family history of ADHD, and an appropriate dosage of medication according to the patients weight. CONCLUSIONS The findings suggest remission as a treatment goal for ADHD therapy by providing an optimal dosage of medication for children and adolescents with ADHD through using an effective and tolerable forced-titration scheme.

Prevalence rates of youths diagnosed with and medicated for adhd in a nationwide survey in Taiwan from 2000 to 2011

AIMS Public controversy regarding the potential overdiagnosis and overmedication of children with attention-deficit/hyperactivity disorder (ADHD) has continued for decades. This study used the National Health Insurance Research Database of Taiwan (NHIRD-TW) to explore trends in ADHD diagnosis in youths and the proportion of those receiving medication, with the aim of determining whether ADHD is overdiagnosed and overmedicated in Taiwan. METHOD Youths (age ≤18 years) who had at least two NHIRD-TW claims records with ADHD diagnosis between January 2000 and December 2011 were selected as the subject cohort. In total, the study sample comprised 145 018 patients with ADHD (mean age at a diagnosis of ADHD: 7.7 ± 3.1 years; 21.4% females). The number of cases of ADHD were calculated annually for each year (from 2000 to 2011), and the number of cases per year who received medication was determined as those with at least one record of pharmacotherapy (immediate-release methylphenidate, osmotic controlled-release formulation of methylphenidate, and atomoxetine) in each year. RESULTS The prevalence rates of a diagnosis of ADHD in the youths ranged from 0.11% in 2000 to 1.24% in 2011. Compared with children under 6 years of age, the ADHD diagnosis rates in children aged between 7 and 12 years (ratio of prevalence rates = 4.36) and in those aged between 13 and 18 years (ratio of prevalence rates = 1.42) were significantly higher during the study period. The prevalence in males was higher than that in females (ratio of prevalence rates = 4.09). Among the youths with ADHD, 50.2% received medications in 2000 compared with 61.0% in 2011. The probability of receiving ADHD medication increased with age. More male ADHD patients received medications that females patients (ratio of prevalence rates = 1.16). CONCLUSIONS The rate of ADHD diagnosis was far lower than the prevalence rate (7.5%) identified in a previous community study using face-to-face interviews. Approximately 40-50% of the youths with ADHD did not receive any medications. These findings are not consistent with a systematic public opinion about overdiagnosis or overmedication of ADHD in Taiwan.

Neurocognitive effects of aripiprazole in adolescents and young adults with schizophrenia

Abstract Background: The use of aripiprazole has been associated with a positive influence on mood and improved cognitive skills and social interactions; however, studies of its effects on young schizophrenic patients have been limited to active symptoms. Aims: This prospective, open-label study investigated the neurocognitive effects of aripiprazole in adolescents and young adults with first and repeated episodes of schizophrenia. Methods: Twenty-three of 42 schizophrenic outpatients aged 12–26 completed a trial of aripiprazole, and its efficacy was determined using the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impressions Severity (CGI-S) and WHO Quality of Life (WHOQOL) scales. Cognitive function was measured with the Cognitive Performance Test (CPT) and Wisconsin Card Sorting Test (WCST) at 4, 12 and 24 weeks of treatment. Results: Results showed statistically significant improvements in BPRS, CGI-S and WHOQOL scores in certain (but not all) subcategories of cognitive measures including CPT detectability and total errors and perseverative errors on the WCST. There were few adverse side-effects. Conclusions: Psychotic symptoms and cognitive skills improved during treatment with aripiprazole in adolescents and young adults with schizophrenia. Patients with first psychotic episodes did better than did those with repeat episodes.

Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population.

Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic components. Several recent genome-wide association (GWA) studies in Caucasian samples have reported a number of gene regions and loci correlated with the risk of ASD—albeit with very little consensus across studies. Methods A two-stage GWA study was employed to identify common genetic variants for ASD in the Taiwanese Han population. The discovery stage included 315 patients with ASD and 1,115 healthy controls, using the Affymetrix SNP array 6.0 platform for genotyping. Several gene regions were then selected for fine-mapping and top markers were examined in extended samples. Single marker, haplotype, gene-based, and pathway analyses were conducted for associations. Results Seven SNPs had p-values ranging from 3.4~9.9*10−6, but none reached the genome-wide significant level. Five of them were mapped to three known genes (OR2M4, STYK1, and MNT) with significant empirical gene-based p-values in OR2M4 (p = 3.4*10−5) and MNT (p = 0.0008). Results of the fine-mapping study showed single-marker associations in the GLIS1 (rs12082358 and rs12080993) and NAALADL2 (rs3914502 and rs2222447) genes, and gene-based associations for the OR2M3-OR2T5 (olfactory receptor genes, p = 0.02), and GLIPR1/KRR1 gene regions (p = 0.015). Pathway analyses revealed important pathways for ASD, such as olfactory and G protein–coupled receptors signaling pathways. Conclusions We reported Taiwanese Han specific susceptibility genes and variants for ASD. However, further replication in other Asian populations is warranted to validate our findings. Investigation in the biological functions of our reported genetic variants might also allow for better understanding on the underlying pathogenesis of autism.

Effectiveness of aripiprazole in adolescents and young adults with schizophrenia spectrum disorders: comparison of first-episode to recurrent psychosis.

The study aims to determine the clinical outcomes of aripiprazole treatment in adolescents and young adults with schizophrenia spectrum disorders.

Polymorphisms of STS gene and SULT2A1 gene and neurosteroid levels in Han Chinese boys with attention-deficit/hyperactivity disorder: an exploratory investigation

This study examined the relationships among polymorphisms of the STS gene and SULT2A1 gene, dehydroepiandrosterone (DHEA) and its sulfated form (DHEA-S), and characteristics of attention-deficit/hyperactivity disorder (ADHD). We used cheek swabs to obtain the genomic DNA of 200 ADHD male probands (mean age: 8.7 years), 192 patients’ mothers and 157 patients’ fathers. Three SNPs in the STS gene (rs6639786, rs2270112, and rs17268988) and one SNP in the SULT2A1 gene (rs182420) were genotyped. Saliva samples were collected from the ADHD patients to analyze DHEA and DHEA-S levels. The behavioral symptoms were evaluated with the Swanson, Nolan, and Pelham, and Version IV Scale for ADHD (SNAP-IV), and the neuropsychological function was assessed using the Conners’ Continuous Performance Tests (CPT). We found the C allele of rs2270112 within the STS gene to be over-transmitted in males with ADHD. Polymorphisms of rs182420 within the SULT2A1 gene were not associated with ADHD. In addition, the C allele carriers of rs2270112 demonstrated significantly higher DHEA-S levels than the G allele carriers. Levels of DHEA were positively correlated with attention as measured by the CPT. These findings support a potential role in the underlying biological pathogenesis of ADHD with regard to STS polymorphisms and neurosteroid levels.

Potential role of pre- and postnatal testosterone levels in attention-deficit/hyperactivity disorder: is there a sex difference?

Objective Both prenatal testosterone (T) exposure and postnatal T levels have been associated with developing neural circuitry and behavioral systems. This study examined the potential correlation between pre- and postnatal T levels and behavioral and neurocognitive profiles of children with attention-deficit/hyperactivity disorder (ADHD). Methods Two hundred ADHD patients with a mean age of 8.7±2.0 years (158 boys and 42 girls) were recruited. The ratio of the length of the right index finger (2D) to that of the right ring finger (4D) (2D/4D ratio) served as a surrogate of prenatal T exposure, and postnatal T was determined using salivary T concentration. Behavioral symptoms were evaluated using the Swanson, Nolan, and Pelham – Version IV Scale for ADHD (SNAP-IV). Neurocognitive function was assessed using the Wechsler Intelligence Scale for Children – Fourth Edition (WISC-IV) and Conners’ Continuous Performance Test (CPT). Results Lower 2D/4D ratios were associated with comorbid disruptive behavior disorders (t=2.15, P=0.033) in all participants. Among the boys with ADHD, neither 2D/4D ratios nor salivary T levels were associated with behavioral symptoms or neurocognitive function. Among the girls with ADHD, the salivary T level was positively correlated with the Perceptual Reasoning Index of the WISC-IV (r=0.48, P=0.001) and the Confidence Index (r=0.37, P=0.017) and Omission Errors of the CPT (r=0.62, P<0.001). Conclusion Findings suggest that a higher prenatal T exposure is associated with a greater risk of developing disruptive behavior disorders, and T may exert differential neurocognitive effects between boys and girls with ADHD. However, the neurobiological mechanisms of T involved in the pathogenesis of ADHD warrant further investigation.