Mortality among long-stay patients with schizophrenia during the setting-up of community facilities under the Yuli model.

Objective: Over the past 15 years, Yuli Veterans Hospital (YVH) in Taiwan has developed the Yuli model to reform long-stay care for psychiatric patients. The development of the Yuli model could be divided into pre-early (1998-1999), early (2000-2006) and late (2007-2008) periods according to the setting-up of the community facilities. In the pre-early period, a vocational rehabilitation program was established for psychiatric patients in YVH. In the later periods, the independent living skills training and the program for social reintegration were instituted in the community facilities. This study aimed to evaluate mortality among the long-stay patients with schizophrenia during the three periods. Methods: In all, 2457 patients with schizophrenia who had been hospitalized for at least one year initially were retrospectively followed from 1 January 1998 to 31 December 2008. Compared with the general population in Taiwan, we calculated the age- and sex-specific standardized mortality ratios (SMRs) of those patients by cause of death during the three periods. Results: Most of the patients were male (81.3%). The mean ± SD age of the patients was 57.83 ± 16.95 years. The all-, natural- and unnatural-cause mortalities of the patients were nearly two times greater than those of the general population during the whole study period. Compared with those in the pre-early and early periods, all patients in the late period had the lowest mortality gaps. In the pre-early, early and late periods, the all-cause SMR were 5.40 (95% confidence interval (CI) = 4.27-6.81), 2.90 (95% CI = 2.20-3.79) and 1.17 (95% CI = 0.54-2.22), respectively, for the 50-69-year-old male patients. Nearly half of all the patients who participated the whole comprehensive rehabilitation program belonged to this sex and age group (N = 156, 46.6%). Conclusions: With the setting-up of community facilities for the comprehensive rehabilitation program, the mortality gaps among the 50-69-year-old male patients apparently decreased using the Yuli model.

A systematic review of combination therapy with stimulants and atomoxetine for attention-deficit/hyperactivity disorder, including patient characteristics, treatment strategies, effectiveness, and tolerability.

OBJECTIVE: The purpose of this article was to systematically review the literature on stimulant and atomoxetine combination therapy, in particular: 1) Characteristics of patients with attention-deficit/hyperactivity disorder (ADHD) given combination therapy, 2) treatment strategies used, 3) efficacy and effectiveness, and 4) safety and tolerability. METHODS: Literature databases (MEDLINE(®), EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, and SciVerse Scopus) were systematically searched using prespecified criteria. Publications describing stimulant and atomoxetine combination therapy in patients with ADHD or healthy volunteers were selected for review. Exclusion criteria were comorbid psychosis, bipolar disorder, epilepsy, or other psychiatric/neurologic diseases that could confound ADHD symptom assessment, or other concomitant medication(s) to treat ADHD symptoms. RESULTS: Of the 16 publications included for review, 14 reported findings from 3 prospective studies (4 publications), 7 retrospective studies, and 3 narrative reviews/medication algorithms of patients with ADHD. The other two publications reported findings from two prospective studies of healthy volunteers. The main reason for prescribing combination therapy was inadequate response to previous treatment. In the studies of patients with ADHD, if reported, 1) most patients were children/adolescents and male, and had a combined ADHD subtype; 2) methylphenidate was most often used in combination with atomoxetine for treatment augmentation or switch; 3) ADHD symptom control was improved in some, but not all, patients; and 4) there were no serious adverse events. CONCLUSIONS: Published evidence of the off-label use of stimulant and atomoxetine combination therapy is limited because of the small number of publications, heterogeneous study designs (there was only one prospective, randomized controlled trial), small sample sizes, and geographic bias. Existing evidence suggests, but does not confirm, that this drug combination may benefit some, but not all, patients who have tried several ADHD medications without success.

Genetic and environmental influences on the Wisconsin Card Sorting Test performance in healthy adolescents: a twin/sibling study.

This study aimed to estimate the relative contributions from genetic and environmental factors to the Wisconsin Card Sorting Test (WCST) performance, a widely used measurement for assessing frontal lobe function. Participants included 350 pairs of twins (257 MZ and 93 DZ) and 47 same-sex sib-pairs, aged 12-16 years, systematically recruited from junior high schools in Taipei. A computerized version of the WCST was administered for each participant and its nine indexes were used for subsequent analysis. Univariate analysis in structural equation modeling was performed for each WCST index using Mx program. The ACE model for each WCST index indicated no significant genetic influence, whereas the shared environmental influence ranged from 30 to 38% for four indexes (Perseverative Errors, Perseverative Responses, Categories Achieved, and Conceptual Level Responses). We concluded that WCST performance might be an indicator more for environmental insult than for genetic influences on frontal lobe function.

Effects of DRD2/ANKK1 gene variations and clinical factors on aripiprazole efficacy in schizophrenic patients.

OBJECTIVES: Aripiprazole, a novel antipsychotic agent, acts as a partial agonist at dopamine D2 receptors (DRD2). We investigate whether its efficacy is predictable by DRD2/ANKK1 gene polymorphisms and clinical factors in Han Chinese hospitalized patients with acutely exacerbated schizophrenia. METHOD: After hospitalization, the patients (n=128) were given aripiprazole for up to 4 weeks. They were genotyped for four functional DRD2/ANKK1 polymorphisms: -141 Ins/Del, Ser311Cys, C957T, and TaqIA. Clinical factors such as gender, age, illness duration, education level, diagnostic subtype, and medication dosage were also recorded. Psychopathology was measured biweekly with the positive and negative syndrome scale (PANSS). The effects of genetic and clinical factors on PANSS performance upon aripiprazole treatment were analyzed by a mixed modeling approach (SAS Proc MIXED). RESULTS: Compared to the patients with TaqI A2/A2 genotype, A1 carriers are associated with superior therapeutic response on positive symptoms after 4-week aripiprazole treatment. Regarding the C957T polymorphism, patients with C/C genotype were associated with poor aripiprazole response for excitement symptoms when compared with T/T patients. The other two polymorphisms, -141 Ins/Del, and Ser311Cys, have no significant effects on PANSS performance. The clinical factors including medication dosage, illness duration, and diagnostic subtype could influence PANSS performance upon aripiprazole treatment. CONCLUSION: This study suggests that DRD2/ANKK1 gene variations and some clinical factors may predict individual response to aripiprazole.

Concomitant use of lamotrigine and aripiprazole increases risk of Stevens-Johnson syndrome?

Stevens-Johnson syndrome is a severe and potentially life-threatening cutaneous reaction associated with lamotrigine. The incidence of developing Stevens-Johnson syndrome during lamotrigine therapy is low. On the basis of the glutamate and dopamine neuron dysregulation hypothesis in schizophrenia, we propose new strategies for the treatment of schizophrenic patients using a glutamate system stabilizer lamotrigine as an adjunctive treatment for the poor responders of a dopamine system stabilizer, aripiprazole. The finding of Stevens-Johnson syndrome in two cases out of three treated with lamotrigine plus aripiprazole, however, has a much higher index of suspicion and it is correct to warn of its possible raised risk. As lamotrigine is currently licensed for the prophylactic treatment of bipolar depression, many of these patients have psychotic features where it would be considered reasonable to add an antimanic atypical antipsychotic such as aripriprazole. The two case reports raised the question about the possible increased risk of Stevens-Johnson syndrome with the combination therapy.

Orally disintegrating olanzapine for the treatment of a manic patient with esophageal stricture plus chronic pharyngitis.

An orally disintegrating tablet formulation of olanzapine (ODT olanzapine) is designed to dissolve rapidly upon contact with saliva. We describe a manic patient who has an esophageal stricture and chronic pharyngitis, two conditions that impede the swallowing of medications. She was successfully treated for her mania with this orally disintegrating formulation. This case report shows that ODT olanzapine may be useful in the psychiatric management of manic and other patients for whom olanzapine is appropriate, and who have an underlying medical condition that impedes swallowing oral medications.

Genetic and environmental influences on schizotypy among adolescents in Taiwan: a multivariate twin/sibling analysis.

This study aimed to examine the relative contribution of genes and environment to psychometrically measured schizotypy and the causes for the covariation between different dimensions of schizotypy in a total of 330 pairs of twins and 36 same-sex sib-pairs aged 12-16 and systematically recruited from junior high schools in Taipei. Twins' zygosity was determined by a combination of DNA typing and physical similarity. Schizotypy was measured using the Perceptual Aberration Scale (PAS) as well as the Schizotypal Personality Questionnaire (SPQ) and its three factors (Cognitive-perceptual Dysfunction, Disorganization, and Interpersonal Dysfunction). Univariate analyses of structural equation modeling using Mx program showed that scores on these schizotypal measures were substantially heritable (h (2) ranging from 41 to 49%), with some genetic effects being non-additive. Multivariate analyses revealed common genetic factors linking between various traits of schizotypy, with bivariate heritability ranging from 50 to 65%. The proportion of the genetic contributions not shared with the other measures of schizotypy ranged from 24% for the Disorganization to 49% for the PAS scores. We concluded that there exist both common and specific genetic factors between the various dimensions of schizotypy, and at least half of their correlations were genetic in nature.

Employment experience in relation to alcohol, tobacco, and betel nut use among youth in Taiwan.

The aim of this study is to assess the association linking employment experience with alcohol, tobacco, and betel nut involvement among youth in Taiwan. In 2004, an outreach program was conducted during weekdays to recruit youth sample in seven major geographic regions. A total of 5886 youth aged 12-18 years drawn from 26 cities or towns were assessed by a two-page anonymous self-administered questionnaire, including sociodemographic characteristics, employment-, development-, and drug-related experiences. In Taiwan, youthful experience of alcohol, tobacco, and polydrug use varies by employment status, work intensity, and job type. Holding a full-time job and working in certain settings (e.g., grocery, restaurants) were found associated with an excess of drug-using behaviors. With taking age, male gender, family context, disposable allowance, and school attendance into account, working youths were two to four times as likely to have recent drug involvement than their non-working counterparts, especially for tobacco and polydrug (OR=3.32, 95% CI: 2.58-4.27, p<0.001; OR=3.76, 95% CI: 2.76-5.13, p<0.001). Youths in the labor force emerge as a subgroup experiencing greater use of alcohol, tobacco, betel nut, and polydrug. Future prevention programs may target this high-risk group to reduce possible drug-related negative consequences in developmental and health domains in Taiwan.

The Taipei Adolescent Twin/sibling Family Study I: behavioral problems, personality features, and neuropsychological performance.

The present study aimed to investigate genetic and environmental influences on behavioral problems, personality features, and neuropsychological performance among adolescents in Taipei, Taiwan. Between 1996 and 1998, with the assistance of the Twin Association and junior high schools in Taipei City, we solicited a list of twins from 51 junior high schools in Taipei. Names, addresses, and telephone numbers of the twins enrolled in these schools were obtained. The vast majority of the recruited twins were between 12 and 16 years old. The recruited twins received assessments for behavioral problems, general and schizotypal personality, and cognitive functions. Their parents rated their children on behavioral/ emotional problems and were assessed on their own general and specific personality. Same-sex sibling pairs (ages vary within 2 years) and their parents from three schools were also recruited to increase sample size for the group with a kinship coefficient of .50. Twins' zygosity was determined by a combination of DNA typing and physical similarity. The Mx program was used to estimate parameters for the full model and its reduced models. The recruitment, measurements, data managements, and published results are described in this article.

A school-based twin study of handedness among adolescents in Taiwan.

This study aimed to evaluate whether twinning might influence handedness and the relative contribution of genetic and environmental factors to handedness in a total of 321 pairs of twins, 36 same-sex sib-pairs, and 1020 singletons, aged 12-16 and systematically recruited from the junior high schools in Taipei. Twins' zygosity was determined by a combination of DNA typing and physical similarity. The direction and consistency of handedness in twins did not differ from that seen in singletons. Compared with the full model containing additive genes (A), shared (C), and non-shared (E) environment, both AE and CE models had equivalently acceptable fit. The contribution from additive genes in the AE model was estimated to be 16% (directional) to 13% (consistent) for the continuous handedness and 34-10% for the categorical one, whereas the corresponding contribution from shared environment in the CE model was 14-14% and 32-11%, respectively. Handedness in adolescents appears to be not influenced by twinning and not substantially heritable, whereas environmental factors, especially those not shared between siblings, are the most important ones for explaining individual variations.

A twin study of competence and behavioral/emotional problems among adolescents in taiwan.

This work reports on a study to evaluate the relative contributions of genetic and environmental factors to both competence scales and behavioral/emotional syndromes as assessed by the Child Behavior Checklist (CBCL). A total of 279 pairs of twins and same-sex sib-pairs aged 12-16 years were recruited from 51 junior high schools in Taipei City, Taiwan. Twins' zygosity was determined by a combination of DNA typing and physical similarity. The Mx program was used to estimate parameters for a full model that contains effects from sex-specific additive genes, shared environment, and nonshared environment for the majority of the scales. The shared environment in the full model was replaced with nonadditive genetic factors for some scales when indicated. All girls' competence and behavioral/emotional syndromes exhibited a substantial heritability (h2 > 0.4), except for Social Competence and Withdrawn. For boys, though the heritability was also >0.4 for some scales (Social and School Competence, Thought Problems, Attention Problems, Delinquent Behavior, and Total Behavior Problems), environmental influences, especially shared environment, were predominant for most of the scales (10 out of 15 scales). Genetic factors are important for explaining adolescent behavioral problems, especially for girls, while shared environmental influences cannot be ignored for boys. Gender differences in heritability exist for various CBCL-based competence and behavioral/emotional problems.