Runs of homozygosity associated with speech delay in autism in a taiwanese han population: evidence for the recessive model.

Runs of homozygosity (ROH) may play a role in complex diseases. In the current study, we aimed to test if ROHs are linked to the risk of autism and related language impairment. We analyzed 546,080 SNPs in 315 Han Chinese affected with autism and 1,115 controls. ROH was defined as an extended homozygous haplotype spanning at least 500 kb. Relative extended haplotype homozygosity (REHH) for the trait-associated ROH region was calculated to search for the signature of selection sweeps. Totally, we identified 676 ROH regions. An ROH region on 11q22.3 was significantly associated with speech delay (corrected p = 1.73×10(-8)). This region contains the NPAT and ATM genes associated with ataxia telangiectasia characterized by language impairment; the CUL5 (culin 5) gene in the same region may modulate the neuronal migration process related to language functions. These three genes are highly expressed in the cerebellum. No evidence for recent positive selection was detected on the core haplotypes in this region. The same ROH region was also nominally significantly associated with speech delay in another independent sample (p = 0.037; combinatorial analysis Stouffer's z trend = 0.0005). Taken together, our findings suggest that extended recessive loci on 11q22.3 may play a role in language impairment in autism. More research is warranted to investigate if these genes influence speech pathology by perturbing cerebellar functions.

A randomized controlled trial of risperidone and olanzapine for schizophrenic patients with neuroleptic-induced tardive dyskinesia.

OBJECTIVE: To compare the efficacy of risperidone and olanzapine in schizophrenic patients with tardive dyskinesia on treatment with first-generation antipsychotics. METHOD: We conducted a 24-week, rater-blinded, flexible-dose study. Sixty patients with DSM-IV schizophrenia (n = 58) or schizoaffective disorder (n = 2) met the DSM-IV research criteria for neuroleptic-induced tardive dyskinesia and were randomly assigned to a risperidone or olanzapine group. The primary outcome was a comparison of the change in the total scores on the Abnormal Involuntary Movement Scale (AIMS) from baseline to study end point between the groups. The study was conducted from July 2000 to June 2004. RESULTS: The mean ± SD doses of risperidone and olanzapine from baseline to study end point were 1.9 ± 0.7 to 4.1 ± 1.4 mg/d and 8.1 ± 2.0 to 12.6 ± 5.4 mg/d, respectively. There were no statistically significant differences in demographic data, severity of tardive dyskinesia, or psychotic symptoms between risperidone and olanzapine groups at baseline assessment. Both groups showed significant improvement in mean ± SD AIMS total scores (risperidone: −7.4 ± 6.9, P < .0001; olanzapine: −6.2 ± 8.0, P = .0002). However, there was a more statistically significant change in the slope of AIMS total scores in the risperidone group than in the olanzapine group (P = .0001). CONCLUSIONS: Our findings demonstrated that olanzapine may not have better potential for tardive dyskinesia improvement than risperidone did. Double-blinded, fixed dose studies with a larger sample size on schizophrenic patients with tardive dyskinesia from different ethnic groups are needed to confirm the results of our study. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00621998

Improved body weight and metabolic outcomes in overweight or obese psychiatric patients switched to amisulpride from other atypical antipsychotics.

Switching to a different second-generation antipsychotic (SGA) with a lower risk of weight gain is recommended for overweight or obese psychiatric patients undergoing SGA treatment. However, there have been no complete reports regarding the long-term metabolic effects of switching to amisulpride. In this open-label 1-year study, we investigated the effects on body weight and other metabolic profiles when psychiatric patients treated with another SGA were switched to amisulpride treatment. Forty-six schizophrenia or schizoaffective inpatients with a body mass index greater than 27 kg/m were enrolled in the switch group. These patients were cross-titrated to amisulpride treatment and followed up for 1 year prospectively. Another 46 inpatients matched with the baseline body mass index of those in the switch group were enrolled as the control group retrospectively. The results showed that the switch group had greater weight loss than the control group (7.80 +/- 6.67 vs 2.60 +/- 6.23 kg, respectively; repeated-measure analysis of variance, P < 0.0005). During the treatment course, the amisulpride-treated patients showed significantly decreased fasting triglyceride, total cholesterol, glucose, and insulin resistance levels; decreased diastolic blood pressure and pulse rate; and a significant increase in high-density lipoprotein cholesterol levels after switching to amisulpride (all with a P < 0.05). The prevalence of metabolic syndrome in amisulpride-treated patients also decreased significantly from 65.2% to 30.4% (McNemar test, P < 0.0005). These findings suggest that switching to amisulpride could be an effective treatment of overweight or obese psychiatric patients treated previously with other SGAs.

Development of a Chinese version of the Suicide Intent Scale.

This study established the psychometric properties of the Chinese version of the Suicide Intent Scale (SIS) in a clinic- and community-based sample of 36 patients and 592 respondents, respectively. Results showed that the Chinese SIS demonstrated good inter-rater and test-retest reliability. Factor analysis generated three factors (Precautions, Planning, and Seriousness) explaining 92.9% of the total variance with high internal consistency. It was moderately correlated with depressive symptoms. Results suggest that the Chinese SIS is a reliable and valid instrument for use in assessing the extent of suicidal intention among subjects with deliberate self-harm in ethnic Chinese populations.

Relationship of attention-deficit-hyperactivity disorder symptoms, depressive/anxiety symptoms, and life quality in young men.

AIM: Attention-deficit-hyperactivity disorder (ADHD) continues to be among the most frequently missed of psychiatric diagnoses in adults because its presentation in adulthood so often mimics those of better-known disorders. The aim of the present study was to examine the relationship between ADHD symptoms, depression/anxiety symptoms, and life quality in young men. METHODS: Nine hundred and twenty-nine draftees into the Taiwanese army completed the Adult ADHD Self-Report Scale (ASRS), the World Health Organization (WHO) Quality of Life-Brief Version, the Epworth Sleepiness Scale, the second edition of the Beck Depression Inventory, and the Beck Anxiety Scale. Based on high ASRS scores, a total of 328 adults (35.3%) were identified as having ADHD: 65 (7.0%) with definite ADHD and 263 (28.3%) with probable ADHD. RESULTS: The 328 subjects in the ADHD group had more severe depressive, anxiety symptoms and daytime sleepiness, and had poorer quality of life than the 601 controls (all P < 0.05). CONCLUSIONS: ADHD should be included in the differential diagnosis for young men presenting with anxiety, depression, daytime sleepiness, and poor quality of life.

Validation of attention-deficit-hyperactivity disorder subtypes among Taiwanese children using neuropsychological functioning.

OBJECTIVE: The findings regarding the validity of attention-deficit-hyperactivity disorder (ADHD) subtypes using neuropsychological functioning have been inconsistent; and no such study has been conducted in an ethnic Chinese population. The aim of the present paper was therefore to examine the validity of attention tasks in distinguishing the ADHD-combined type (ADHD-C) from the ADHD-inattention type (ADHD-I), as compared to children without ADHD in Taiwan. METHODS: Participants included 52 children with ADHD-C, 17 with ADHD-I, and 52 controls, aged 7-10 years. The clinical diagnosis of DSM-IV ADHD was further confirmed by a standardized psychiatric interview. Four attention components were examined: sensory selection, response selection, capacity/focus, and sustained attention, using the Cancellation Test, Digit Span, Trail-Making Test (TMT), Continuous Performance Test (CPT), and Circle-Tracing Test. Behaviour symptoms were rated by the parents, teachers, and investigators. RESULTS: Compared to children without ADHD, children with ADHD scored significantly higher in parent-reported and investigator-rated behavioural symptoms, and performed worse in the four domains of attention. Multiple comparisons indicated that children with ADHD-C had a worse performance on most tests than children with ADHD-I, except that children with ADHD-I had more off-target errors on the TMT with alphanumeric sequencing than children with ADHD-C. CONCLUSIONS: Attention tests can distinguish Taiwanese children with ADHD from those without ADHD, and these tests also demonstrate different profiles between the ADHD-C and ADHD-I groups. Further investigation on this topic should include the ADHD-hyperactivity-impulsivity subtype (ADHD-HI) and increase sample sizes of the children with ADHD-I and ADHD-HI.

A randomized, double-blind, placebo-controlled clinical trial on once-daily atomoxetine in Taiwanese children and adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVE: The aim of this study was to assess the efficacy and safety of the once-daily atomoxetine compared with placebo in pediatric patients with attention-deficit/hyperactivity disorder (ADHD) in Taiwan. METHOD: The study sample included 106 patients aged 6-16 years who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria of ADHD randomly assigned to atomoxetine once daily (n = 72) and placebo once daily (n = 34) in a double-blind, 6-week treatment study. The primary efficacy measure was the total score of the ADHD Rating Scale-IV Parents Version: Investigator Administered and Scored. The secondary efficacy measures included the Clinical Global Impressions--ADHD--Severity and Chinese Conner's Parent and Teacher Rating Scale--Revised: Short Form. Data were analyzed on an intent-to-treat basis and a last-observation-carried-forward approach. RESULTS: The two treatment groups did not differ in demographics and baseline measures. Compared to the placebo group, the atomoxetine group showed significantly greater reductions in ADHD-related symptoms according to the ratings of investigators, parents, and teachers. The treatment effect size of the primary efficacy measure was 0.70 at the end of study. Adverse events reported significantly more frequently with atomoxetine were decreased appetite (36.1%) and nausea (16.6%). No drug-related serious adverse event was observed. CONCLUSIONS: Once-daily atomoxetine is an effective, well-tolerable, and safe treatment for children and adolescents with ADHD in Taiwan.

Association between sleep problems and symptoms of attention-deficit/hyperactivity disorder in young adults.

STUDY OBJECTIVE: To examine the association between sleep-related problems and symptoms of attention-deficit/hyperactivity disorder (ADHD) in a community sample of young adults in Taiwan. DESIGN: A college-based cross-sectional survey. PARTICIPANTS: Two thousand two hundred eighty-four first-year college students (aged 18-20) in a university in Taiwan. MEASUREMENTS AND RESULTS: Each student completed a questionnaire regarding sleep schedule (self-estimated total sleep duration and sleep need), sleep problems (dyssomnia, parasomnia, and snoring), and the Chinese version of the Adult ADHD Self-Report Scale. Subjects were grouped separately for the inattention and hyperactivity subscales into highly likely ADHD (2.3%, 0.7%), probable ADHD (21.3%, 5.7%), and probably non-ADHD (76.4%, 93.6%) groups according to the scoring scheme of the subscales of the Adult ADHD Self-Report Scale. Results showed that, for both inattention and hyperactivity symptoms, the highly likely ADHD and probable ADHD groups were more likely than the non-ADHD group to have a variety of current and lifetime sleep problems. No significant difference in sleep problems was found between the highly likely ADHD and probable ADHD groups. Inattention, but not hyperactivity, was associated with greater sleep need and greater difference between sleep need and self-estimated nocturnal sleep duration. Hyperactivity, but not inattention, was associated with decreased nocturnal sleep duration. CONCLUSIONS: Consistent with prior findings from children and adolescents, ADHD symptoms in young adults are related to sleep problems. Further studies on adults with ADHD should help to refine our understanding of the causal basis for any implications of this association.

Psychiatric and psychosocial predictors of substance use disorders among adolescents: longitudinal study.

BACKGROUND: Few studies have prospectively examined psychosocial and psychiatric predictors of adolescent substance use disorders simultaneously. AIMS: To identify psychosocial and psychiatric predictors of substance use disorders in adolescence. METHOD: School children aged 12 years (s.d.=0.3) free from any substance use disorder at grade 7 (n=428) were assessed in three consecutive years, using a standardised psychiatric interview. Their baseline psychosocial information was also collected. The outcome was the onset age of a substance use disorder. The Cox regression model was used for data analysis. RESULTS: The most significant predictive factors for adolescent substance use disorder included male gender, attention-deficit hyperactivity disorder, conduct disorder and sibling use of tobacco. Three protective factors against such morbidity included living in a household with two parents, a good academic grade at grade 7 and objection to the use of substances. CONCLUSIONS: Early intervention for disruptive behaviour disorders and specific psychosocial risk factors might prevent substance use disorders in early adolescence.

Determinants of adherence to methylphenidate and the impact of poor adherence on maternal and family measures.

OBJECTIVE: The aim of this study was to examine the association between adherence to immediate-release methylphenidate (IR MPH) and maternal psychological distress, parenting style, parent- child relationship, and perceived family support. METHODS: The sample consisted of 307 children with attention-deficit hyperactivity disorder (ADHD) (271 boys and 36 girls), 6-17 years of age, who had been treated with IR MPH for the past 6 months. The measures included the Chinese Health Questionnaire, Parental Bonding Instrument, Family APGAR, and Home Behaviors of the Social Adjustment Inventory for Children and Adolescents. RESULTS: Reasons for poor adherence (n = 79; 25.7%) included forgetting medication (72.7%), the medication having no effect (20.0%), and refusing medication (12.7%). Increased age and three-times-daily administration were the major predictors for poor adherence to IR MPH. Poor adherence was associated with increased degree of maternal psychological distress, indifferent parenting, maternal overprotection/control, poor family support, decreased interaction with parents, and increased problems at home. CONCLUSIONS: Findings indicate that multiple daily dosing of MPH increases the likelihood of poor adherence, particularly in adolescents, and that poor adherence is associated with impaired maternal/family process. Once-daily administration of MPH is necessary to improve adherence and to decrease the possible exacerbation of tense parent-child relationships caused by poor drug adherence.

Development of a chinese version of the Yale-Brown obsessive compulsive scale for heavy drinking.

BACKGROUND: Measurement of craving is an important component in the investigation of the etiology and clinical pictures of alcoholism and dependence of other substances in different cultures. The aim of this study was to develop a Chinese version of the Yale-Brown Obsessive Compulsive Scale for heavy drinking (YBOCS-hd-C), the instrument most frequently used in assessing the severity of alcohol craving in Taiwan. METHODS: Four hundred twenty Han Chinese (220 with alcohol use disorders) and 218 Bunun aborigines (150 with alcohol use disorders) in Taiwan were interviewed by mental health professionals with the YBOCS-hd-C and a Chinese version of the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry to establish the psychiatric diagnosis. Validity and reliability of the YBOCS-hd-C were examined. RESULTS: The YBOCS-hd-C was found to have acceptable interrater reliability (intraclass correlation, 0.89-0.96), internal consistency (Cronbach's alpha = 0.99), construct validity, concurrent validity, and cross-cultural validity. The correlations between 10 items of the YBOCS-hd-C and 11 items of the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry adjusted for age, gender, and ethnicity ranged from 0.39 to 1.00. The YBOCS-hd-C also discriminated effectively among individuals with alcohol dependence, alcohol abusers, and normal drinkers. CONCLUSIONS: This study demonstrated that the YBOCS-hd-C is a reliable and valid instrument for assessing the extent of craving for alcohol in Taiwanese Han and Bunun individuals.

A 3-year panel study of mental disorders among adolescents in Taiwan.

OBJECTIVE: This study investigated the prevalence and changing trends of mental disorders and the effects of gender and urbanization among adolescents in Taiwan. METHOD: A random sample of seventh-grade students (N=1,070) was recruited from one urban and one rural junior high school in which 1,051 (98.2%) and 1,035 (96.7%) were reassessed in the second and third years, respectively. A two-stage case identification was conducted by mental health professionals with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version, supplemented by information from the Child Behavior Checklist. RESULTS: The weighted 3-month prevalence rates across the 3 consecutive years for overall psychiatric disorders were 20.3%, 22.7%, and 14.8%, respectively. The most prevalent psychiatric condition was attention deficit hyperactivity disorder (ADHD) in the first 2 years and substance use disorders in the third. During the 3 years, the rates for ADHD, specific phobia, and social phobia decreased, and the rates for major depression and substance use disorders, conversely, increased. Although conduct disorder, ADHD, and substance use disorders were more prevalent among boys, the rates for major depression, social phobia, specific phobia, and adjustment disorder were higher among girls. Rural adolescents had higher rates of conduct disorder, oppositional defiant disorder, and substance use disorders than their urban counterparts. CONCLUSIONS: Our findings are similar to those of previous studies among adolescents in prevalence rates, changing trends of most mental disorders, and gender effects. The differential changing trends in various diagnostic groups may imply the importance of specific measures for prevention during adolescence.

Mental illness and accidental death. Case-control psychological autopsy study.

BACKGROUND: Few studies have systematically investigated the psychiatric antecedents of accidental death. AIMS: To examine the patterns of psychiatric morbidities contributing to accidental death in three ethnic groups (Han, Ami and Atayal) in Taiwan. METHOD: A case-control psychological autopsy was conducted among 90 accidental deaths (randomly selected from a total of 413) and 180 living controls matched for age, gender, ethnicity and area of residence in Taiwan. RESULTS: The risk of accidental death was significantly associated with alcohol use disorder and with other common mental disorders. When jointly considered, it was greatest when these two types of disorders co-existed, followed by common mental disorders alone. The risk of accidental death increased with the number of comorbid conditions. CONCLUSIONS: The prevention of accidental death should be incorporated into preventive psychiatry, not just for alcohol use disorder, but also for all other common mental disorders.