Characteristic Similarities of Irritability Between Autism and Disruptive Mood Dysregulation Disorder.

Objective: Irritability in children with autism spectrum disorder (ASD) is prominent and often leads to distress to both autistic children and their families. However, the nature of irritability in autism and the difference from nonautistic children have rarely been examined. This study aimed to investigate the clinical characteristics of irritability in autism, and to compare the symptom profiles with those of disruptive mood dysregulation disorder (DMDD) in nonautistic children. Methods: Fifty-six children aged 7-17 years (mean age 10.36 ± 3.05) were recruited into this study (21 with DMDD, 21 with high-functioning autism [hfASD], and 14 healthy volunteers [HV]). Their parents completed the Aberrant Behavior Checklist-Irritability (ABC-I) subscale and the Strengths and Difficulties Questionnaire (SDQ) parent report form. The ABC-I subscale was analyzed as a whole and broken into subsets (ABC-I-Irritability, ABC-I-Agitation, and ABC-I-Crying). The symptom profiles of irritability and the association with psychosocial difficulties were compared between groups. Results: The ABC-I-Irritability scores of children with hfASD closely matched to those of children with DMDD. In addition, both DMDD and hfASD groups could be differentiated from HV group in five of the six items except "depressed mood." However, in the ABC-I-Agitation scale, children with DMDD, but not hfASD, had higher scores in "Aggressive to other patients and staff" and "Stamps feet while banging objects or slamming doors" than HV. Regarding psychosocial outcomes, irritability in children with DMDD and hfASD were associated with emotional problems as measured by the SDQ. Moreover, irritability in DMDD was associated with conduct problems, and the hfASD group exhibited the similar trend. Conclusions: Symptom profiles of irritability and the associated emotional and conduct problems in children with hfASD were similar to those of DMDD in the nonautistic population. Future studies are warranted to explore the underlying neurophysiological mechanisms of irritability between autistic and nonautistic children for further insight into the nature of irritability in autism.

Genetic and environmental contributions to co-occurring physical health conditions in autism spectrum condition and attention-deficit/hyperactivity disorder.

BACKGROUND: Autism spectrum condition and attention-deficit/hyperactivity disorder (ADHD) are associated with a range of physical health conditions. The aim of this study was to examine the etiological components contributing to co-occurring physical health conditions in autism and ADHD. METHODS: In this nationwide Child and Adolescent Twin Study in Sweden, we analyzed data from 10,347 twin pairs aged 9 and 12. Clinical diagnoses of autism, ADHD, and physical health conditions were identified through the Swedish National Patient Register. Subclinical phenotypes of autism and ADHD were defined by symptom thresholds on a standardized parent-interview, the Autism-Tics, ADHD, and Other Comorbidities inventory. Associations between physical health conditions and autism/ADHD phenotypes were examined using generalized estimating equations. Bivariate twin models were applied to estimate the extent to which genetic and environmental risk factors accounted for physical health comorbidities. RESULTS: Similar patterns of association with physical health conditions were found in clinical and subclinical autism/ADHD, with odds ratios ranging from 1.31 for asthma in subclinical ADHD to 8.03 for epilepsy in clinical autism. The estimated genetic correlation (ra) with epilepsy was 0.50 for clinical autism and 0.35 for subclinical autism. In addition, a modest genetic correlation was estimated between clinical autism and constipation (ra = 0.31), functional diarrhea (ra = 0.27) as well as mixed gastrointestinal disorders (ra = 0.30). Genetic effects contributed 0.86 for mixed gastrointestinal disorders in clinical ADHD (ra = 0.21). Finally, subclinical ADHD shared genetic risk factors with epilepsy, constipation, and mixed gastrointestinal disorders (ra = 0.30, 0.17, and 0.17, respectively). LIMITATIONS: Importantly, since medical records from primary care were not included in the registry data used, we probably identified only more severe rather than the full range of physical health conditions. Furthermore, it needs to be considered that the higher prevalence of physical health conditions among autistic children and children with ADHD could be associated with the increased number of medical visits. CONCLUSIONS: Shared genetic effects contribute significantly to autism and ADHD phenotypes with the co-occurring physical health conditions across different organ systems, including epilepsy and gastrointestinal disorders. The shared genetic liability with co-occurring physical health conditions was present across different levels of autism and ADHD symptom severity.

Association of cumulative early medical factors with autism and autistic symptoms in a population-based twin sample.

Although highly heritable, environment also contributes to the etiology of autism spectrum disorder (ASD), with several specific environmental factors previously suggested. A registry-linked population-based twin cohort of 15,701 pairs (586 individuals with an ASD diagnosis), was established within the Child and Adolescent Twin Study in Sweden. Participants were evaluated for autistic symptoms at age 9 using the Autism-Tics, ADHD and other Comorbidities parental interview. A series of binary cut-offs indicated whether participants scored over various ASD symptom percentiles. Three early medical factors previously associated with ASD, beyond familial confounding (low birth weight, congenital malformations and perinatal hypoxia), were summed up creating an individual cumulative exposure load. A series of unconditional logistic regressions between all individuals and conditional regressions within twin pairs were performed for each outcome and exposure level. Between all individuals increasing cumulative early exposure loads were associated with increasing risk of ASD diagnosis (OR 3.33 (95%CI 1.79-6.20) for three exposures) and autistic symptoms (ranging from OR 2.12 (1.57-2.86) for three exposures at the 55th symptom percentile cut-off to OR 3.39 (2.2-5.24) at the 95th). Within twin pairs, the association between three exposures and an ASD diagnosis remained similar, but not statistically significant (OR 2.39 (0.62-9.24)). Having a higher load of early cumulative exposure was consistently associated with autistic symptoms after adjusting for familial confounding and sex (OR 3.45 (1.66-7.15) to OR 7.36 (1.99-27.18)). This study gives support to the cumulative stress hypothesis of ASD, and the dimensional model regarding environmental exposures, after adjustment for familial confounding.

Headache in ADHD as comorbidity and a side effect of medications: a systematic review and meta-analysis.

There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This systematic review and meta-analysis investigated the co-occurrence of headache in children with ADHD, and the effects of ADHD medications on headache. Embase, Medline and PsycInfo were searched for population-based and clinical studies comparing the prevalence of headache in ADHD and controls through January 26, 2021. In addition, we updated the search of a previous systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs) on ADHD medications on June 16, 2020. Trials of amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with a placebo arm and reporting data on headache as an adverse event, were included. Thirteen epidemiological studies and 58 clinical trials were eligible for inclusion. In epidemiological studies, a significant association between headache and ADHD was found [odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.63-2.46], which remained significant when limited to studies reporting ORs adjusted for possible confounders. The pooled prevalence of headaches in children with ADHD was 26.6%. In RCTs, three ADHD medications were associated with increased headache during treatment periods, compared to placebo: atomoxetine (OR = 1.29, 95% CI = 1.06-1.56), guanfacine (OR = 1.43, 95% CI = 1.12-1.82), and methylphenidate (OR = 1.33, 95% CI = 1.09-1.63). The summarized evidence suggests that headache is common in children with ADHD, both as part of the clinical presentation as such and as a side effect of some standard medications. Monitoring and clinical management strategies of headache in ADHD, in general, and during pharmacological treatment are recommended.

Behavioral and biological divergence in monozygotic twin pairs discordant for autism phenotypes: A systematic review.

Background: Non-shared environment (NSE) effects account for around one-third of the etiology of autism spectrum disorder (ASD). However, the knowledge of mechanisms and phenotypic profiles associated with NSE in ASD is scarce. Methods: A systematic search was conducted using Embase, MEDLINE, and PsycINFO for studies published in English between 1990 and August 2020 using co-twin control design to compare behavioral and biological phenotypes among monozygotic (MZ) twin pairs concordant/discordant for ASD, clinical autism symptoms, or autistic traits. Risk of bias was assessed through a modified Newcastle-Ottawa Scale. Results: Twenty six articles were included. Differential DNA methylation and gene expression were found among ASD discordant twins; however, genetic results were inconsistent. Neurological disorders and early medical events were associated with ASD and autistic traits, while no within pair differences were found for minor physical anomalies or head circumference. Structural and functional brain imaging studies and research on social and other cognitive/behavioral functions were inconclusive. Risk of bias assessment found that all studies used the same exposure (or outcome) measures to collect data for participants and most used either secure health-related records or structured interviews for ascertainment of exposure; however, only a handful of studies representative of the population from which they were drawn. Formal assessment of risk of publication bias (i.e., funnel plot) was not possible. Conclusions: Our results suggest that NSE in ASD could be associated with heterogeneous postzygotic genetic mechanisms and manifest as a range of biological and behavioral phenotypes. Extant findings were limited by relatively few studies, small sample sizes, and methodological diversity. More research is needed on co-occurring biological and behavioral phenotypes using a consistent format for designing, analyzing, and reporting MZ ASD discordant twin studies in order to further examine the role of NSE in the etiology of ASD.

Neurological disorders in autism: A systematic review and meta-analysis.

LAY ABSTRACT: Neurological disorders, such as epilepsy and cerebral palsy, have been reported to occur among individuals with autism beyond chance and may have an impact on daily living across the lifespan. Although there has been research investigating neurological disorders in autism, the findings are not always conclusive. Previous summaries of existing studies have not evaluated the full range of neurological disorders. This study aimed to comprehensively explore the neurological problems appearing in autism to provide updated information that is needed for better healthcare and support in this population. We looked at already published studies focusing on risk or frequency of neurological disorders in autism. Our results suggest that individuals with autism are more likely than the general population to have a range of neurological disorders, including epilepsy, macrocephaly, hydrocephalus, cerebral palsy, migraine/headache, and inborn abnormalities of the nervous system. In order to provide individualized healthcare and support of high quality to individuals diagnosed with autism, health care professionals and other support providers need to be attentive to neurological complications. To further improve our understanding about the link between autism and neurological disorders, future research should follow the neurological health of children who are diagnosed with or are at increased likelihood of autism.

The association between ADHD and physical health: a co-twin control study.

Attention-deficit/hyperactivity disorder (ADHD) has been associated with increased risk for physical comorbidity. This study used a twin cohort to investigate the association between physical diseases and phenotypic variations of ADHD. A twin cohort enriched for ADHD and other neurodevelopmental conditions were analysed. The Attention Problems subscale of the Child Behavior Checklist/Adult Behavior Checklist (CBCL/ABCL-AP) was used to measure the participants' severity of ADHD symptoms. Physical health issues were obtained with a validated questionnaire and were tested in relation to ADHD symptom severity in a co-twin control model. Neurological problems were significantly associated with a diagnosis of ADHD. A conditional model for the analysis of within-twin pair effects revealed an inverse association between digestive problems and the severity of ADHD symptoms, after adjusting for co-existing autism spectrum disorder and ADHD medications. Our findings suggest that individuals with ADHD are susceptible to neurological problems, why a thorough neurological check-up is indicated in clinical practice for this population. In addition, health conditions of digestive system could be considered as a non-shared environmental factor for behavioral phenotypes in ADHD. It supports the possible role of gut-brain axis in the underpinnings of ADHD symptoms, at least for a subgroup of individuals with certain genetic predisposition.

The Association Between Somatic Health, Autism Spectrum Disorder, and Autistic Traits.

This study used a twin cohort to investigate the association of autism spectrum disorder (ASD) and autistic traits with somatic health. A total of 344 twins (172 pairs; mean age 15.56 ± 5.62 years) enriched for ASD and other neurodevelopmental conditions were examined. Medical history and current physical problems were collected with a validated questionnaire to determine twin's somatic health. The Social Responsiveness Scale (SRS-2) was used to measure the participant's severity of autistic traits. Identified somatic health issues with significant within-twin pair differences were tested in relation to both ASD diagnosis and autistic traits in a co-twin control model. Twins with ASD exhibited more neurological and immunological health problems compared to those without ASD (p = 0.005 and p = 0.004, respectively). The intra-pair differences of neurological conditions and SRS-2 score were significantly correlated in monozygotic twins differing for autism traits (r = 0.40, p = 0.001), while the correlation was not found for immunological problems. In addition, a conditional model for analysis of within-twin pair effects revealed an association between neurological problems and clinical ASD diagnosis (Odds ratio per neurological problem 3.15, p = 0.02), as well as autistic traits (ß = 10.44, p = 0.006), after adjusting for possible effects of co-existing attention deficit hyperactivity disorder and general intellectual abilities. Our findings suggest that neurological problems are associated with autism, and that non-shared environmental factors contribute to the overlap for both clinical ASD and autistic traits. Further population-based twin studies are warranted to validate our results and examine in detailed the shared genetic and environmental contributions of neurological problems and ASD.

Potential Negative Effects of Dextromethorphan as an Add-On Therapy to Methylphenidate in Children With ADHD.

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.

Irritability and Maladaptation Among Children: The Utility of Chinese Versions of the Affective Reactivity Index and Aberrant Behavior Checklist-Irritability Subscale.

OBJECTIVES: Irritability is among the most bothersome emotional symptoms in children. It often leads to mental health services referral, significant impairment, and distress to their families. Although there is increasing scientific evidence supporting the existence of extreme irritability in the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5) diagnosis of disruptive mood dysregulation disorder, few studies have investigated the measurement of irritability in children. This pilot study aimed to examine the psychometric properties of the Chinese version of the Affective Reactivity Index (ARI) and the Aberrant Behavior Checklist (ABC)-irritability subscale. In addition, we investigated adaptive difficulties among children with irritability. METHODS: A total of 97 children and adolescents 6 to 17 years of age (M = 10.20, SD = 2.70) were recruited from the psychiatric outpatient department of a university hospital in Taipei. The participants completed the Chinese version of the ARI self-report form and the Social Adjustment Inventory for Children and Adolescents (SAICA). Their parents completed the ARI parent report form, the Chinese version of the ABC-irritability subscale, and the Child Behavior Checklist. Diagnostic interviews were administered based on diagnostic criteria of DSM-5 to confirm the participants' psychiatric diagnoses. RESULTS: The Chinese ABC-irritability subscale and the parent and self-report scales of the Chinese ARI showed good test-retest reliability, internal consistency, and concurrent validity. Scores from the ABC-irritability subscale and two forms of the ARI were all significantly correlated with aggressive behaviors, anxious/depressed symptoms, and social problems. In addition, irritability among children was significantly associated with maladjustment in school, with peer problems, and with problems at home. CONCLUSIONS: Our findings suggest that irritability may be associated with impaired social adaptive functioning among children and adolescents. The Chinese version of the ARI and the ABC-irritability subscale are useful for measuring irritability in both clinical and research settings in the Chinese population.

Aripiprazole/Methylphenidate Combination in Children and Adolescents with Disruptive Mood Dysregulation Disorder and Attention-Deficit/Hyperactivity Disorder: An Open-Label Study.

OBJECTIVES: Disruptive mood dysregulation disorder (DMDD) is characterized by nonepisodic irritability and has a high rate of comorbidity with attention-deficit/hyperactivity disorder (ADHD). This is the first study to explore the effects of aripiprazole combined with methylphenidate on clinical symptoms and cognitive functions in patients with DMDD and ADHD. METHODS: Patients with DMDD and ADHD (the DMDD-ADHD Group, n = 24; aged 7-17 years) completed a 6-week, open-label trial of aripiprazole and methylphenidate. The pre- and posttreatment outcome measures included the parent-rated Swanson, Nolan, and Pelham Scale-version IV, Child Behavior Checklist, and self-reported Beck Youth Inventories-II, as well as a neuropsychological battery composed of the Children's Color Trail Test and Conner's Continuous Performance Test. The comparison group consisting of patients with ADHD (the ADHD Group, n = 27) was recruited to investigate the differences in clinical and neuropsychological profiles between the two groups at baseline. RESULTS: The DMDD-ADHD Group showed worse irritability, disruptive behaviors, anxious/depressed symptoms, and social problems relative to the ADHD Group at baseline assessments. The combination treatment significantly improved irritability, externalizing symptoms, depression, anxiety, attention, social problems, and reaction time variability. The effect sizes of reductions in parent-rated irritability, oppositional defiant symptoms, and inattention were comparable (Cohen's d = 1.26, 1.11, and 1.40, respectively). CONCLUSIONS: This pilot study showed the tolerability of the aripiprazole/methylphenidate combination by patients with DMDD and ADHD and its efficaciousness for treating clinical symptoms and for improving cognitive function. Further randomized, controlled, cross-over studies are needed.

Internet Addiction among Adolescents May Predict Self-Harm/Suicidal Behavior: A Prospective Study.

OBJECTIVE: To explore the role of Internet addiction in the development of self-harm/suicidal behavior among adolescents after 1-year of follow-up. STUDY DESIGN: We conducted this 1-year, prospective cohort study of 1861 adolescents (mean age 15.93 years) attending a senior high school in Taiwan; 1735 respondents (93.2%) were classified as having no history of self-harm/suicidal attempts in the initial assessment and were referred to as the "noncase" cohort. The Chen Internet Addiction Scale was used to identify individuals with Internet addiction. The participants were evaluated for self-harm/suicidal behavior again 1 year later and the "noncase" cohort was selected for statistical analysis. To examine the relationship between Internet addiction and self-harm/suicidal behavior, multivariate logistic regression analysis was performed using Internet addiction at baseline as the predictor for newly developed self-harm/suicidal behavior in the next year, after adjustment for potential confounding variables. RESULTS: The prevalence rate of Internet addiction at baseline was 23.0%. There were 59 students (3.9%) who were identified as having developed new self-harm/suicidal behaviors on follow-up assessments. After controlling for the effects of potential confounders, the relative risk of newly emerging self-harm/suicidal behavior for participants who were classified as Internet addicted was 2.41 (95% CI 1.16-4.99, P = .018) when compared with those without Internet addiction. CONCLUSIONS: Our findings indicate that Internet addiction is prospectively associated with the incidence of self-harm/suicidal behavior in adolescents.

Impact of depressive/anxiety symptoms on the quality of life of adolescents with ADHD: a community-based 1-year prospective follow-up study.

Adolescents with attention-deficit/hyperactivity disorder (ADHD) often exhibit functional impairment even those having less visible symptoms. Therefore, it is of great clinical importance to identify ADHD symptoms among adolescents in the community. Furthermore, little is known regarding the role of internalizing symptoms in their quality of life. Thus, this study aimed to screen ADHD in a sample of high school students using the Adult ADHD Self-report Scale (ASRS) and to investigate the impact of internalizing symptoms on their well-being. In the first year, adolescents aged 15-17 years old from a senior high school (N = 1947) completed the Adult ADHD Self-rating Scale (ASRS), Wender Utah Rating Scale, Impulsiveness Scale, Beck's Depression Inventory and Beck's Anxiety Inventory. In the second year, the World Health Organization Quality of Life-BREF was applied for the measurement of their psychosocial outcomes. Results showed that adolescents with higher ASRS scores manifested more severe concurrent depressive and anxiety symptoms. ADHD symptoms among these adolescents were significantly associated with poorer quality of life 1 year later (p < 0.001). And both depressive and anxiety symptoms were mediators in the relationship between ADHD symptoms and quality of life. The finding of this study supports that the concurrent internalizing symptoms may underlie the negative relations between ADHD symptoms and quality of life in adolescents in the community. The application of ASRS in adolescents may help clinicians in early intervention for their ADHD problems as well as emotional symptoms.

Mood disturbance in adolescents screened by the Mood Disorder Questionnaire predicts poorer social adjustment.

PURPOSE: Early-onset bipolar disorder is associated with a more severe illness course and poorer outcome. Its identification in adolescents may provide the opportunity for adequate intervention to improve global functioning and long-term prognosis. Thus, this study aimed to screen mood disturbance in a sample of high school students using Mood Disorder Questionnaire (MDQ) and follow up their adaptive functioning 1 year later. METHODS: In the first year, adolescents aged 15-17 years old from a Taiwanese senior high school (N = 1,151) completed the Chinese version of MDQ, the Impulsiveness Scale, and a set of questions about risky behaviors. A subgroup of respondents (N = 184) picked randomly were interviewed to validate the diagnosis of bipolar disorder. In the second year, the Social Adjustment Inventory for Children and Adolescents was applied for the same sample of subjects for the measurement of their adaptive functions. RESULTS: The intraclass correlation coefficient and the Cronbach α coefficient of the MDQ were .68 and .61, respectively. MDQ score of at least 7 showed modest sensitivity (.57) and specificity (.64) for bipolar disorder. Higher MDQ score predicted risky behaviors in adolescents at baseline measurement. MDQ score was found significantly correlated with Impulsiveness Scale total score. In follow-up evaluation, participants with an MDQ score of ≥7 had poorer social adjustment. CONCLUSIONS: Our findings suggest that untreated mood disturbance among adolescents leads to impaired social adaptive functioning in the next year. The application of MDQ in adolescents may help clinicians in early intervention for their emotional disturbance.

Effects of a selective educational system on fatigue, sleep problems, daytime sleepiness, and depression among senior high school adolescents in Taiwan.

OBJECTIVE: The aim of the study reported here was to clarify the effects of academic pressure on fatigue, sleep problems, daytime sleepiness, and depression among senior high school adolescents in Taiwan. METHODS: This cross-sectional study enrolled 757 senior high school adolescents who were classified into four groups: Grade 1 (n=261), Grade 2 (n=228), Grade 3T (n=199; Grade 3 students who had another college entrance test to take), and Grade 3S (n=69; Grade 3 students who had succeeded in their college application). Fatigue, sleep quality, daytime sleepiness, and depression were assessed using the Chinese version of the Multidimensional Fatigue Symptom Inventory - Short Form, Pittsburgh Sleep Quality Index-Taiwan Form, the Chinese version of the Epworth Sleepiness Scale, and the Chinese version of the Beck Depression Inventory(®)-II (BDI-II), respectively. RESULTS: Physical, emotional, and mental fatigue scores were all higher in higher-grade groups. The Grade 3T (test) students had the worst fatigue severity, and the Grade 3S (success) students had the least fatigue severity. More than half of the students (60.9%) went to bed after 12 am, and they had on average 6.0 hours of sleep per night. More than 30% of the students in Grade 2 (37.3%) and Grades 3T/S (30.2%/30.4%) possibly had daily sleepiness problems. The students in Grade 3T had the worst BDI-II score (13.27±9.24), and the Grade 3S students had a much lower BDI-II score (7.91±6.13). CONCLUSION: Relatively high proportions of fatigue, sleep problems, daytime sleepiness, and depression among senior high school adolescents were found in our study. The severities of fatigue, sleep problems, and depression were significantly diminished in the group under less academic stress (Grade 3S). Our findings may increase the understanding of the mental health of senior high school students under academic pressure in Taiwan. Further large sample size and population-based study should be done for better understanding about this topic.

The efficacy and safety of once-daily quetiapine extended release in patients with schizophrenia switched from other antipsychotics: an open-label study in Chinese population.

BACKGROUND: Non-adherence to antipsychotic medication in schizophrenic patients is common and associated with symptom relapse and poorer long-term outcomes. The risk factors for treatment non-adherence include dosing frequency and complexity. Besides, slower dose titration in an acute schizophrenic episode may lead to attenuated efficacy. Therefore, the convenient dosage regimen and rapid initiation scheme of quetiapine extended release (XR) were expected to provide better effectiveness and promote adherence in patients with schizophrenia. This study was implemented to assess the efficacy and safety of once-daily quetiapine XR in schizophrenic patients with switched from other antipsychotics which were suboptimal due to insufficient efficacy or tolerability. METHODS: This was a 12-week, open-label study conducted in the Chinese population in Taiwan. Patients who had a score of 4 (moderate) or greater on any of the 7 items of the Positive and Negative Syndrome Scale (PANSS) Positive Symptom Subscale and needed to switch from previous antipsychotics were recruited. Quetiapine XR was administered at 300 mg on day 1, 600 mg on day 2 and up to 800 mg after day 2. From day 8 until the end of the study, the dose of quetiapine XR was adjusted within 400-800 mg per day, depending on the clinical response and tolerance of the patients. The variable of the primary outcome was the change from baseline to Week 12 in PANSS total and subscale scores. Secondary outcome was the baseline-to-endpoint difference in the Clinical Global Impression-Severity (CGI-S) scores of the participants. RESULTS: Sixty-one patients were recruited and 55.7% of them completed the study. The mean changes in the PANSS total score and CGI-S score showed significant improvement (-18.4, p < .001 and -1.0, p < .001, respectively). Four patients (6.7%) experienced adverse events including headache, exacerbation of psychosis and dysuria. The use of concomitant anticholinergics decreased from 15.0% to 8.3%. CONCLUSIONS: The results of our investigation implicated that quetiapine XR was an effective and well tolerated alternative for Chinese schizophrenic patients with previous suboptimal treatment. Future large-scale studies are warranted to validate our results. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02142556 . Registered 15 May 2014.