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Objectives: The association between older-age bipolar disorder and cognitive impairments may be mediated by vascular burden. The aim of the study was to examine the difference of cognitive function between older people with late-onset bipolar disorder (LOBD) and early-onset bipolar disorder (EOBD) by considering rigorous vascular risk burden evaluation, comprehensive cognitive tests, and relevant biochemistry data. Methods: We recruited 95 outpatients aged over 55 with a DSM-IV-TR diagnosis of bipolar I disorder. Fifty had LOBD, defined by age of onset after 40. Cognitive function was evaluated through a battery of tests assessing verbal memory, attention/speed, visuospatial function, verbal fluency, and cognitive flexibility. Vascular risk assessments included individual disorders, 10-year Framingham cardiovascular risk scores, and serum levels of homocysteine, vitamin B12, folate, and triiodothyronine. Results: No differences were observed between LOBD and EOBD on any cognitive test after adjusting for potential confounders. In addition to age and educational years, multiple linear regression analyses indicated significantly negative associations between serum homocysteine levels and cognitive performances in attention, psychomotor speed, verbal memory, and executive function. Conclusions: Among older people with bipolar disorder, LOBD is not associated with more cognitive dysfunction in this study. However, higher serum homocysteine levels were significantly associated with worse cognitive performance in this particular group. Clinicians therefore have to pay attention to the cognitive function in older bipolar patients with higher levels of homocysteine.

Differences in cognitive function have been suggested in people with late-life depression between those with early- (EOD) and late-onset (LOD), possibly reflecting different etiologies. The cutoff point for EOD and LOD was the first depressive episode before age 60 or later. However, depressive symptoms at the time of disorder are important confounders. The study aimed to compare cognitive function in older people with EOD and LOD in the euthymic state. A sample of 135 participants aged 60+ with a history of major depressive disorder in remission, received neuropsychological evaluation including tests of memory, attention, processing speed, visuospatial function, language, and executive function. Individual test scores and a derived composite score were investigated as dependent variables against age of onset using multiple linear regressions adjusted for potential confounders, including residual depressive symptoms. We found EOD (N = 67) and LOD (N = 68) groups did not differ significantly in overall composite cognitive scores after adjustment. Of individual test scores, only those for immediate recall were significantly lower in participants with EOD compared to LOD. In conclusion, the study found no associations between cognitive function and age of onset in this sample of people with depressive disorder in remission. Active or residual depressive symptoms might have confounded this relationship in previous research.

Objective The aim of this study was to compare the treatment effectiveness between long-acting injectable risperidone and long-acting injectable first-generation antipsychotics among patients with bipolar disorder. Method We conducted a retrospective cohort study using Taiwan's National Health Insurance Research Database. Patients with bipolar disorder aged 15 years or higher, who were newly administered long-acting injectable antipsychotics between June 1, 2004 and December 31, 2011 were included. The clinical outcome indexes were hospitalization for any mood, manic/mixed, or depressive episodes. In addition, the all-cause discontinuation of long-acting injectable antipsychotic treatment was also assessed. Results A total of 3916 patients with bipolar disorder were extracted. Compared with risperidone, the use of first-generation antipsychotics was associated with a higher rate of hospitalization for any mood episode and major depressive episode. However, there was no statistically significant difference in treatment discontinuation rate between risperidone and first-generation antipsychotics. Limitations Information for the severity of mood symptoms, social support, life style, neurological and metabolic adverse effect was not available in this database. In addition, we only measured severe mood episodes with hospitalization as our outcome index. It may not be possible to generalize our findings to mild mood episodes. Conclusions Our findings suggested that patients treated with long-acting injectable risperidone might be superior to first-generation antipsychotics in the rate of psychiatric hospitalization.

Bipolar disorder is an important psychiatric disorder with different disease phases. The pharmacological treatment is complicated, and is updated frequently as new research evidence emerges. For the purpose of international collaboration, research, and education, the Taiwan consensus of pharmacological treatment for bipolar disorders was initiated by the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN) – the Bipolar Chapter, which was established in August 2010 and approved as a member of International Society of Bipolar Disorder. TSBPN is the country member of the World Federation of Societies of Biological Psychiatry (WFSBP). The development of the Taiwan consensus for bipolar disorder was mainly based on the template of WFSBP Guidelines, with references to other international guidelines including the Canadian Network for Mood and Anxiety Treatments, and British Association for Psychopharmacology. We have also added Taiwanese experts’ experience, Taiwan national health insurance data, and the indications for the pharmacological treatment of bipolar disorder given by the Taiwan Department of Health, to emphasize the balance between efficacy and safety, and to make this consensus a concise, empirical, and important reference for clinical psychiatric practice.

Bipolar disorder (BD) is burdensome for patients and healthcare systems. This study evaluated changes in concomitant medication patterns, healthcare utilization, and costs after the initiation of risperidone long-acting injection (RLAI) treatment among BD patients.287 BD patients receiving regular RLAI treatment for 1 year were identified from the Taiwan National Health Insurance Research database during 2007-2012. The bootstrapping procedure was performed to create 1000 samples to generate normally distributed data. The paired t-tests with a correction for multiple comparisons using Bonferroni correction were used to compare the proportion of patients of concomitant psychiatric medication and resource use and costs between pre- and post-RLAI periods. Rapid and non-rapid cycling stratification was performed based on the number of change-in-mood episodes within 1 year prior to the index date.The mean annual dose of RLAI was 638.41mg, which was equal to an average dose of 24.6mg every 2 weeks. The prevalence of concomitant use of conventional antipsychotics, atypical antipsychotics, lithium, and antidepressants decreased from the pre-RLAI period to the post-RLAI period by 23.75%, 31.91%, 1.29%, and 7.08%, respectively. RLAI use decreased emergency room (ER) visits, hospital admissions, length of hospital stay, and non-medication costs (all P0.0001). The cost savings with RLAI were attributed to lower hospitalization costs in spite of higher medication costs. Moreover, rapid cycling patients (n=36) demonstrated greater reduction in ER and inpatient services with RLAI than non-rapid cycling patients (n=251).Of the patients who initiated RLAI, 15% of them who had regular treatment were included. Furthermore, data on measures of symptom severity, side effects, and hyperprolactinemia were not available.BD patients had lower inpatient and ER utilization, and non-medication costs after using RLAI. In addition, RLAI use decreased the number of change-in-mood episodes in rapid cycling patients; which provides additional insights into the treatment of rapid cycling BD patients.

Background: Lower concentrations of n23 PUFAs have been reported to be associated with cognitive impairment and dementia, but also with depression—itself a potential risk factor for cognitive decline. Objective: The aims of this study were to investigate associations between n23 PUFA concentrations in erythrocyte membrane or plasma and cognitive function in an at-risk sample of older people with previous major depression and to explore specificity with respect to cognitive domains. Design: A cross-sectional sample of 132 eligible participants who had recovered from major depression (mean 6 SD age: 67.8 6 6.6 y) were enrolled from outpatient psychiatric services. A series of cognitive tests and a structured questionnaire were administered. Fasting blood samples were collected for n23 PUFA measurements. Results: Higher EPA and total n23 PUFA concentrations and a lower ratio of arachidonic acid to EPA in erythrocyte membranes were associated with a higher cognitive composite score: independent of age and sex, but no longer significant after adjustment for education. No associations were found with plasma concentrations of any fatty acid. Considering individual cognitive tests, the strongest and most consistent correlations were found between immediate recall and concentrations of total n23 PUFAs and a-linolenic acid (ALA) in erythrocytes, which were observed only in participants with recurrent depression. Conclusions: Total erythrocyte n23 PUFA concentrations are positively associated with cognitive function, particularly immediate recall, in older people with previous depression. Lower concentrations of n23 PUFAs or ALA in erythrocyte membranes may be good predictors for cognitive impairment in older people with previous recurrent depression. Am J Clin Nutr 2012;95:420–7.

Gau C-S, Chang C-J, Tsai F-J, Chao P-F, Gau SS-F. Association between mood stabilizers and hypothyroidism in patients with bipolar disorders: a nested, matched case-control study. Bipolar Disord 2010: 12: 253–263. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: This study investigated whether lithium, carbamazepine, and valproate increased the risk for hypothyroidism using Taiwan’s National Health Insurance Dataset. Methods: The sample included 557 bipolar disorder patients with incident hypothyroidism first diagnosed between 1998 and 2004, and 2,228 sex-, age-, and index date-matched bipolar disorder patients without hypothyroidism from 1996–2004. We compared the use of lithium, carbamazepine, and valproate before the onset of hypothyroidism between the two groups using a conditional logistical regression model. Results: Compared with patients who had never used any of the three mood stabilizers, patients were more likely to have hypothyroidism if they only used carbamazepine [odds ratio (OR) = 1.68; 95% confidence interval (CI): 1.07–2.65]; or comedication of lithium and valproate (OR = 2.40; 95% CI: 1.70–3.40), lithium and carbamazepine (OR = 1.52; 95% CI: 1.10–2.08), and three mood stabilizers (OR = 2.34; 95% CI: 1.68–3.25). There was a dose-response relationship between the number of mood stabilizers and risk for hypothyroidism (OR = 1.34, 95% CI: 1.21–1.49) and a significant interaction between lithium and valproate on the risk for hypothyroidism (p = 0.020). Conclusions: Our findings indicate that lithium, carbamazepine, and valproate may increase the risk for hypothyroidism, particularly if combined, and suggest regular monitoring of thyroid function and monotherapy of mood stabilizers for treating patients with bipolar disorders.

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

Aims: Atypical antipsychotics are increasingly used in the management of acute mania. This study was conducted to investigate the efficacy and tolerability of zotepine compared to haloperidol in combination with a mood stabilizer (lithium or valproate) for treatment of acute mania. Methods: This was a multi-center, randomized, rater-blinded, parallel-group, flexible-dose study. Forty-five hospitalized patients with moderate-to-severe manic, bipolar disorder (DSM-IV) were randomly assigned to a zotepine or a haloperidol 4-week treatment group. Results: There was no significant between-group difference in the Young Mania Rating Scale total scores between the zotepine and haloperidol groups (−23.7 ± 12.1 vs –22.3 ± 11.0, respectively). The adverse events in both groups were mild to moderate. The haloperidol group reported a higher incidence of treatment-related adverse events, especially parkinsonism and akathisia, compared to the zotepine group. Serum uric acid decreased more in the zotepine group than in the haloperidol group. Conclusion: In combination with a mood stabilizer, zotepine appears to be as effective as haloperidol in treating moderate-to-severe mania in the acute phase, but has the advantages of lowering hyperuricemia and fewer extrapyramidal side-effects. Double-blinded studies with larger sample sizes are warranted to confirm these findings.

In this paper, topology optimization problems with three types of body forces are considered: gravitational force, centrifugal force and inertia force. All these body forces are design dependent as they vary with the redistribution of materials during topology optimization process. In this study, a total mean compliance formulation is used to produce the stiffest structure under both external and body forces. Sensitivity analysis is carried out by the adjoint method. Finally, de-sign examples are presented and compared to show the effects of body forces on the optimized results.

In this paper, the layout of structures under design-dependent pressure loading is optimized using a topology optimization approach. In contrast to topology optimization problems with conventional static external loading, the position and direction of pressure loading are changing with topology of structure during optimization iterations. In order to model the changing structural surface boundaries under design-dependent pressure loading, a pseudo equal-potential function is introduced. Design sensitivity analysis is derived from the adjoint method. Three examples solved by the proposed method are presented.

Objective: This study investigated the association between 2 mood stabilizers (carbamazepine and valproate) and other medications (including other anticonvulsants) and the risks of erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) among patients with bipolar disorder. Methods: Using the data of patients with bipolar disorder between March 1997 and December 2004 from the Psychiatric Inpatient Medical Claims databank, we identified 72 patients with bipolar disorder who had an inpatient or outpatient diagnosis of EM, SJS, or TEN by the International Classification of Diseases, Ninth Revision, Classical Modification code 695.1 and 288 controls with the absence of EM, SJS, or TEN diagnosis who were matched for sex, age, and index day. The use of carbamazepine, valproate, and other medications during the 60 days before the index date of diagnosis of EM, SJS, or TEN were compared. Results: Results showed that carbamazepine (odds ratio, 3.7; 95% confidence interval, 2.0-6.8) and valproate use (odds ratio, 2.2; 95% confidence interval, 1.2-4.2) significantly predicted EM, SJS, or TEN. Other significant predictors for EM, SJS, or TEN included other anticonvulsants (phenytoin, phenobarbital, and lamotrigine), cephalosporin, some nonsteroid anti-inflammatory drugs (acetic acid derivatives and fenamates [mefenamic acid]), salicylates, and acetaminophen. The most predictive exposures were carbamazepine, valproate, other anticonvulsants, and acetaminophen. We also found that the combination of carbamazepine and acetaminophen further increased the risk for the occurrence of EM, SJS, or TEN. There was no interaction effect from age and sex. Conclusions: Our study suggests that carbamazepine and valproate as well increase the risk for EM, SJS, or TEN. We should be especially cautious about the combined use of carbamazepine and acetaminophen.

A 24-week, randomized, double-blind placebo-controlled study was carried out to test the feasibility of using omega-3 polyunsaturated fatty acids (PUFAs) monotherapy in people with cognitive impairment and to explore its effects on cognitive function and general clinical condition in these participants. Twenty three participants with mild or moderate Alzheimer's disease and twenty three with mild cognitive impairment were randomized to receive omega-3 PUFAs 1.8 g/day or placebo (olive oil). The data of 35 (76%) participants with at least one post-treatment visit was analyzed. There were no severe adverse effects in either group and it suggests that omega-3 PUFAs were well tolerable in this population. The treatment group showed better improvement on the Clinician's Interview-Based Impression of Change Scale (CIBIC-plus) than those in the placebo group over the 24 week follow-up (p=0.008). There was no significant difference in the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog) change during follow-up in these two groups. However, the omega-3 fatty acids group showed significant improvement in ADAS-cog compared to the placebo group in participants with mild cognitive impairment (p=0.03), which was not observed in those with Alzheimer's disease. Higher proportions of eicosapentaenoic acid on RBC membranes were also associated with better cognitive outcome (p=0.003). Further studies should be considered with a larger-sample size, diet registration, higher dosages, comparisons between different combinations of PUFAs, and greater homogeneity of participants, especially those with mild Alzheimer's disease and mild cognitive impairment.

This study investigates acculturation and other antecedent psychiatric and socio-environmental risk factors for posttraumatic stress disorder (PTSD) in one aboriginal group (the Bunun) exposed to an earthquake disaster in Taiwan. Respondents (n = 196) were assessed 5 months after the disaster, using a Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry and the Taiwan Aboriginal Acculturation Scale. Four risk factors exerted independent effect on the risk of PTSD, including magnitude of the earthquake, subsequent traumas, antecedent major depressive disorder and acculturation status. Public mental health programs need to consider the liability to PTSD in populations with different ethnicity and socio-cultural environments.

Energy harvesting devices based on the piezoelectric effect that converts ambient energy to electric energy is a very attractive energy source for remote sensors and embedded devices. Although topology optimization has been applied to the design of piezoelectric transducers, the locations of piezoelectric materials are predefined and only the optimal layout of elastic materials is considered. In this paper, both elastic materials as well as piezoelectric materials are considered for the design of energy harvesting devices under the topology optimization formulation. The objective function for this study is to maximize the energy conversion factor. The sensitivities of both stored strain energy and electrical energy are derived by the adjoint method. Examples of energy harvesting devices are presented and discussed using the proposed method.

This paper presents an automated method to generate thin-walled packaging structures with reinforcement. This method first obtains a thin-walled design space compose of hexahedral elements, which covers the models to be packaged without undercut effect. After the proper boundary conditions are assigned by designers, topology optimization is applied to identify the optimal placement of reinforcement. This automated method can also be used to generate foam packaging structures. Design examples are presented to demonstrate the efficiency of this method.

Apolipoprotein E epsilon-4 (APOE ε4) allele, methylenetetrahydrofolate reductase (MTHFR C677T), and methionine synthase (MTR A2756G) were tested their associations with cognitive impairment in people with late-life depression (LLD).People with LLD were assessed by mini-mental state examination and were examined the distribution of APOE ε4 allele, MTHFR, and MTR polymorphisms.Odds ratio of MTR 2756 AA to MTR 2756 AG and GG genotypes for the risk of cognitive impairment was 5.80 (95% confidence interval = 1.18-28.50; P = 0.03).People with LLD carrying MTR2756 AA genotype have higher risk of cognitive impairment than those carrying G allele.

Background: Polymorphisms within intron 7 of the tryptophan hydroxylase (TPH1) gene were found to be associated with alcohol dependence in different ethnic groups, including the aboriginal Bunun group in Taiwan. This study aimed to identify genetic variants at the TPH1 locus and to examine their associations with alcoholism. We hypothesized that the polymorphism of TPH1 gene is functional and influences the human circadian rhythm to contribute to the pathophysiology of alcohol dependence. Methods: DNA from the Taiwanese Han and Bunun was subjected to sequence for screening genetic variation in the coding and promoter regions of the TPH1 locus. Polymorphisms among individuals with alcohol dependence and control subjects in two ethnic groups in Taiwan were investigated. Results: Three variants in the TPH1 promoter region were identified, and the markers are in complete linkage disequilibrium in both populations. Positive associations at both allelic and genotypic levels were obtained between case and control groups in the Bunun. Expression studies demonstrated that the variants indeed affected reporter gene activity in human choriocarcinoma and colon adenocarcinoma cell lines. Conclusions: Polymorphisms in the promoter region may influence the function of the TPH1 gene and further influence the proclivity of alcohol dependence in one ethnic group in Taiwan. The associations between TPH1 genotypes and alcoholism may deserve further investigation.

Background: Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders, such as depression, anxiety, migraine, substance abuse, and alcoholism. The human serotonin receptor 1B, encoded by the HTR1B gene, is a presynaptic serotonin autoreceptor that plays a role in regulating serotonin synthesis and release. Because the linkage of antisocial alcoholism to the HTR1B gene was recently reported in two populations, it was of interest to identify genetic variants at the HTR1B locus and study their association with alcoholism in the Taiwanese Han population. Methods: We sequenced DNA from Taiwanese Han to screen for genetic variation in the coding, promoter, and partial 3′ untranslated regions of the HTR1B locus of 158 alcohol-dependent cases with withdrawal symptoms and 149 control subjects, who either never drank or drank only occasionally and in low quantities. Results: Seven variants were identified. Positive associations were found between variant A-161T and alcohol dependence at both the allelic and genotypic level. In addition, an expression study showed that the A-161T variant affected reporter gene activity. Conclusions: Our results support an association between HTR1B and alcohol dependence. The HTR1B A-161T polymorphism may be valuable both as a functional and as an anonymous genetic marker for HTR1B .

The authors compared sustained attention deficits measured by the Continuous Performance Test in patients with various affective disorders and patients with schizophrenia and examined whether Continuous Performance Test deficits in patients with affective disorders improve with remission of affective disorder symptoms.Patients with schizophrenia (N=41), major depression without psychotic features (N=22), bipolar disorder without psychotic features (N=22), and bipolar disorder with psychotic features (N=46) completed Continuous Performance Test sessions with an undegraded version of the test and a 25% degraded version in which the stimulus images were visually distorted. Subjects were also interviewed with the Chinese version of the Diagnostic Interview for Genetic Studies. All inpatients with schizophrenia (N=41) and bipolar disorder (N=15) were assessed both at admission and discharge. Subjects' Continuous Performance Test scores were standardized in comparison with scores for a community sample of 345 subjects, with adjustment for age, sex, and level of education.Compared with the general population, all patient groups except the group with nonpsychotic major depression were significantly impaired in their ability to discriminate target stimuli from nontarget stimuli on the Continuous Performance Test. Patients with schizophrenia had the severest impairment, followed by patients with bipolar disorder with psychotic features and those with bipolar disorder without psychotic features. From admission to discharge, Continuous Performance Test deficits in schizophrenia remained unchanged, but inpatients with bipolar disorder showed significant improvement on the degraded Continuous Performance Test. All patients adopted a similar response criterion (the amount of perceptual evidence the person requires to decide that a stimulus is a target) to that in the general population, except that the patients with schizophrenia had a less stringent response criterion during the degraded Continuous Performance Test.Continuous Performance Test deficits are stable vulnerability indicators for schizophrenia, mediating indicators for bipolar disorder, and state-dependent indicators for major depression.

The goal of this study is to investigate associations between subjective memory complaint and objective cognitive performance in older people with previous major depression±a highrisk sample for cognitive impairment and later dementia. A cross-sectional study was carried out in people aged 60 or over with previous major depression but not fulfilling current major depression criteria according to DSM-IV-TR. People with dementia or Mini-Mental State Examination score less than 17 were excluded. Subjective memory complaint was defined on the basis of a score ≧4 on the subscale of Geriatric Mental State schedule, a maximum score of 8. Older people aged equal or over 60 without any psychiatric diagnosis were enrolled as healthy controls. Cognitive function was evaluated using a series of cognitive tests assessing verbal memory, attention/speed, visuospatial function, verbal fluency, and cognitive flexibility in all participants. One hundred and thirteen older people with previous major depression and forty-six healthy controls were enrolled. Subjective memory complaint was present in more than half of the participants with depression history (55.8%). Among those with major depression history, subjective memory complaint was associated with lower total immediate recall and delayed verbal recall scores after adjustment. The associations between subjective memory complaint and worse memory performance were stronger in participants with lower depressive symptoms (Hamilton Depression Rating Scale score

Lithium has been a first-line choice for maintenance treatment of bipolar disorders to prevent relapse of mania and depression, but many patients do not have a response to lithium treatment.We selected subgroups from a sample of 1761 patients of Han Chinese descent with bipolar I disorder who were recruited by the Taiwan Bipolar Consortium. We assessed their response to lithium treatment using the Alda scale and performed a genomewide association study on samples from one subgroup of 294 patients with bipolar I disorder who were receiving lithium treatment. We then tested the single-nucleotide polymorphisms (SNPs) that showed the strongest association with a response to lithium for association in a replication sample of 100 patients and tested them further in a follow-up sample of 24 patients. We sequenced the exons, exon-intron boundaries, and part of the promoter of the gene encoding glutamate decarboxylase-like protein 1 (GADL1) in 94 patients who had a response to lithium and in 94 patients who did not have a response in the genomewide association sample.Two SNPs in high linkage disequilibrium, rs17026688 and rs17026651, that are located in the introns of GADL1 showed the strongest associations in the genomewide association study (P=5.50×10(-37) and P=2.52×10(-37), respectively) and in the replication sample of 100 patients (P=9.19×10(-15) for each SNP). These two SNPs had a sensitivity of 93% for predicting a response to lithium and differentiated between patients with a good response and those with a poor response in the follow-up cohort. Resequencing of GADL1 revealed a novel variant, IVS8+48delG, which lies in intron 8 of the gene, is in complete linkage disequilibrium with rs17026688 and is predicted to affect splicing.Genetic variations in GADL1 are associated with the response to lithium maintenance treatment for bipolar I disorder in patients of Han Chinese descent. (Funded by Academia Sinica and others.).

The strong thermal hysteresis of thermoelectric power (TEP) in Pr0.5(Sr, Ca)0.5MnO3 is observed. A simple estimation shows that the electrostatic energy between Mn3+/Mn4+ alone cannot account for the large shift of Tco with changing A size. Based on our experimental evidence, we attribute the distinct features exhibited in the thermal hysteresis to the manifestation of the underlying competition between the delocalization and localization effects assisted respectively by the double exchange interaction and the charge ordering. The observed features include the following: (1) the A-size effect can depress Tco by as much as 70 K for Pr0.5Sr0.5-xCaxMnO3; (2) large thermal hysteresis of resistivity and TEP are exhibited in Pr0.5Sr0.5-xCaxMnO3; (3) for x = 0.3 and 0.4, the thermal hysteresis is larger than those of x = 0.1 and 0.5 and (4) magnetic field induces a large shift in Tco.

The temperature dependent thermoelectric power (TEP) for a series of superconducting Y(Ba 2− x Sr x )Cu 3 O 6.95 with x =0 to 0.8 has been investigated. We have kept the oxygen content at the optimal value (6.95±0.02) and have changed the lattice parameters by Sr-doping to study the strain dependent TEP. We have observed that a hump occurs at 240 K for all samples except that with x =0. With increasing the Sr-doping level, S shifts to a higher value and changes its sign from negative to positive. This study demonstrates that the sign as well as the absolute value of TEP has been affected by the lattice strains.

To help determine whether sustained attention deficits as measured with the Continuous Performance Test (CPT) are stable vulnerability indicators of schizophrenia, we compared the CPT performance of schizophrenic patients before and after treatment with risperidone or haloperidol. In this double blind trial, 56 schizophrenic patients were randomly assigned to a 12-week regimen of either risperidone or haloperidol, after a 1-week washout period. The patients undertook two sessions of the CPT (undegraded and 25% degraded) twice, one at the end of the washout period and the other at the end of the study. Thirty-eight patients completed the study, 19 in each group. Both groups experienced significant improvements in clinical symptoms, and the risperidone group showed no change in the severity of extrapyramidal symptoms. Despite those improvements, the CPT performance indexes did not change significantly from the beginning to the end of the study. These findings indicate that sustained attention deficits might be stable vulnerability indicators of schizophrenia.

Twenty drug-naïve patients with obsessive-compulsive disorder (OCD) were compared with matched controls on their performance of the Continuous Performance Test (CPT). There was no difference on any measure of the CPT in the two groups. Higher obsession scores, rather than compulsion scores, were associated with poorer sensitivity of the CPT in drug-naïve OCD patients.

Positive and negative symptom (NGS) dimensions were examined for their concordance in 46 coaffected schizophrenic sib-pairs. Results showed that the symptom dimensions of negative symptoms (NGS), delusion-hallucination (DHS), and thought disorganization (TDS) could be formulated. Discrete genetic endowment of these three symptom dimensions was not found as shown by the low concordance in sib pair analysis (kappa = 0.20–0.30). Thirty-seven pairs (80.4%) and 21 pairs (45.7%) had liability, defined by the presence of NGS in any one member of the coaffected sib-pairs, of NGS of “any degree,” and of “severe degree” in 46 sib-pairs, respectively. Both groups had high prevalence (59.1–81.0%) of positive symptoms. Another 9 (19.6%) and 25 (54.3%) pairs had no liability of NGS of “any degree” or of “severe degree” out of 46 sib-pairs, respectively. These two groups had high concordance (kappa = 0.45–1.00) of TDS or DHS between coaffected sib-pairs. Based on the results, it is hypothesized that schizophrenia, as defined by DSM-III-R, may consist of two subtypes: one has liability of NGS and a high prevalence of positive symptoms, while the other has only positive symptoms. Am. J. Med. Genet. 74:1–6, 1997. © 1997 Wiley-Liss, Inc.

Backgrounds Apolipoprotein E epsilon-4 (APOE e4) allele, methylenetetrahydrofolate reductase (MTHFR C677T), and methionine synthase (MTR A2756G) were tested their associations with cognitive impairment in people with late-life depression (LLD). Methods People with LLD were assessed by mini-mental state examination and were examined the distribution of APOE e4 allele, MTHFR, and MTR polymorphisms. Results Odds ratio of MTR 2756 AA to MTR 2756 AG and GG genotypes for the risk of cognitive impairment was 5.80 (95% confidence interval = 1.18–28.50; P = 0.03). Conclusion People with LLD carrying MTR2756 AA genotype have higher risk of cognitive impairment than those carrying G allele. © 2016 Wiley Publishing Asia Pty Ltd

Background It remains unclear whether depression in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) during pegylated interferon-based therapy is associated with the virus, drug or ethnic background. We aimed to perform a prospective study to evaluate the clinical course of depression and its predictors in consecutive non-cirrhotic CHB and CHC patients of the same ethnicity receiving pegylated interferon-based therapy. Methods The occurrence and severity of depression were actively assessed by the Hamilton Depression Rating Scale before therapy and at weeks 2, 4, 6, 8, 10, 12 and every 4 weeks during treatment until the end of therapy. Extensive numbers of variables (repeated measurements, time variables and interactions between all variables) were included in generalized estimating equations to analyse the predictors of depression. Results A total of 158 consecutive patients (73 CHB and 85 CHC patients) were enrolled. Depression (Hamilton Depression Rating Scale ≥11) occurred in a biphasic pattern at treatment weeks 2-10 and weeks 16-36. Treatment weeks 12 predicts less depression, suggesting the predictability of the time variable during treatment on depression. Furthermore, CHC or pre-existing depression is an independent predictor of depression in these patients ( PConclusions Depression occurred in a biphasic pattern during pegylated interferon-based therapy and should be early and actively assessed, especially in patients with CHC or pre-existing depression.

Backgrounds Depression in late life often follows a chronic course with residual depressive and anxiety symptoms. Levels of omega-3 polyunsaturated fatty acids (PUFAs) have been found to be depleted in people with major depression in the acute stage. Additionally, lower omega-3 PUFA levels have been suggested to be associated with anxiety. The aim of this study was to investigate whether PUFAs levels (omega-3 or omega-6) are correlated with residual depressive or anxiety symptoms in older people with previous depression. Methods Participants aged 60 years or over with previous major depression in remission were enrolled from outpatient psychiatric services of four hospitals. Participants with residual depressive symptoms were defined as the Hamilton Depression Rating Scale (HDRS) scores > 5, and those with anxiety were defined as sum of scores for the two anxiety subscale of HDRS≧2. The levels of fatty acids in erythrocyte membranes and in plasma were measured separately by gas chromatography. Results One hundred and thirty two older people with previous major depression (mean age of 68 years, range 60–86 years) were analyzed. Erythrocyte membrane linoleic acid levels had a curvilinear association with depressive symptoms and anxiety symptoms. Plasma linoleic acid levels were found to have a negative linear relationship with depressive symptoms. No significant associations were found between any omega-3 fatty acid level and depressive or anxiety symptoms. Conclusion Linoleic acid levels may be a possible biomarker for residual depression and anxiety in older people with previous depression. Possible clinical applications need further investigation.

Objective To evaluate the overall long-term effectiveness of aripiprazole in patients with schizophrenia in a general psychiatric practice setting in Taiwan. Methods This was a prospective, open-label, multicenter, post-market surveillance study in Taiwanese patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder requiring a switch in antipsychotic medication because current medication was not well tolerated and/or clinical symptoms were not well controlled. Eligible patients were titrated to aripiprazole (5-30 mg/day) over a 12-week switching phase, during which their previous medication was discontinued. Patients could then enter a 52-week, long-term treatment phase. Aripiprazole was flexibly dosed (5-30 mg/day) at the discretion of the treating physicians. Efficacy was assessed using the Clinical Global Impression scale Improvement (CGI-I) score, the Clinical Global Impression scale Severity (CGI-S) score, The Brief Psychiatry Rating Scale (BPRS), and the Quality of Life (QOL) scale, as well as Preference of Medicine (POM) ratings by patients and caregivers. Safety and tolerability were also assessed. Results A total of 245 patients were enrolled and switched from their prior antipsychotic medications, and 153 patients entered the 52-week extension phase. In all, 79 patients (32.2%) completed the study. At week 64, the mean CGI-I score was 3.10 and 64.6% of patients who showed response. Compared to baseline, scores of CGI-S, QOL, and BPRS after 64 weeks of treatment also showed significant improvements. At week 12, 65.4% of subjects and 58.9% of caregivers rated aripiprazole as better than the prestudy medication on the POM. The most frequently reported adverse events (AEs) were headache, auditory hallucinations and insomnia. A total of 13 patients (5.3%) discontinued treatment due to AEs. No statistically significant changes were noted with respect to fasting plasma glucose, lipid profile, body weight, and body mass index after long-term treatment with aripiprazole. Conclusions Although the discontinuation rate was high, aripiprazole was found to be effective, safe and well tolerated in the long-term treatment of Taiwanese patients with schizophrenia who continued to receive treatment for 64 weeks.

Gradient search methods for linkage synthesis have difficulty on the design convergence due to the non-convexity and non-uniqueness characteristics on linkage design. Although evolutionary optimization approach can solve non-convex problems and produce multiple optimal solutions, it cannot be applied to linkage synthesis easily because a general and efficient method for mechanism analysis is not available. In order to automate the linkage synthesis process, a novel linkage analysis method, called the Constrained Superposition Method (CSM), is presented in this paper. The CSM is based on the concept of Finite Element Analysis. The CSM can analyze any linkage mechanism with Single-Input-Single-Output (SISO). To further improve the efficiency of evolutionary optimization process, two feasibility checks are introduced to ensure the connectivity and mobility. Finally, four linkage synthesis examples are presented and discussed to demonstrate the effectiveness of this method.Copyright © 2008 by ASME

In this paper, topology optimization is used to study the design of piezoelectric actuator with in-plane motion. Two case studies are reported, the maximization of the in-plane motion toward a pre-defined direction and the maximization of the output force. In addition to volume density as design variable used in the conventional topology optimization, a new design variable, electrode density, is introduced to model the electrode topology on the piezoelectric plate surface. Based on the electrode potential model, the relation between the nodal potential and the electrode density is established. Sensitivity analyses of objective function with respect to volume density and electrode density are derived from the adjoint method. Examples of optimized piezoelectric actuators from the proposed method are presented and discussed.Copyright © 2007 by ASME

This paper presents an efficient method to generate packaging space that can be used to create molded foam. This method first reduces the number of facets presenting the product and then detects heights of supporting lines from an evenly spaced mesh grid on the bottom space of a pre-defined bounding box. The height of each supporting line is further relaxed and smoothed to form the final supporting surface. Based on the supporting surface, an STL format is created so it can be fabricated using RP machines. Three examples are presented to demonstrate this method.Copyright © 2006 by ASME

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 α= 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.

Background: Nonselective opioid antagonists reduce alcohol consumption under various experimental situations, and several association studies have examined possible roles of opioid receptor mu (OPRM), delta (OPRD), and kappa (OPRK) genes in the development of alcohol dependence. Methods: We examined 20 single nucleotide polymorphisms (SNPs) across the OPRM, OPRD, and OPRK genes in 158 alcohol-dependent subjects and 149 controls. Differences in allele frequency and genotype distribution between case subjects and controls, as well as the deviation from Hardy-Weinberg equilibrium, were examined using Fisher's exact tests. Results: No significant difference in either allele or genotype frequency was found between case subjects and controls for each of the SNPs. Conclusions: Our findings do not support a possible role of the opioid receptor genes for the proclivity to alcohol dependence in the Taiwanese Han.

OBJECTIVE: To describe a patient who developed visual perception distortion after a single dose of zolpidem. CASE SUMMARY: A 50-year-old Asian woman had been prescribed conjugated estrogen 1 tablet daily for hormone replacement therapy and tricalcium phosphate twice daily for osteoporosis. One day, she took zolpidem 10 mg for insomnia as well as acetaminophen 500 mg for headache at bedtime and began to have visual perception distortion (e.g., the shapes of objects were twisted, houses were crooked) within 20 minutes, lasting for approximately 30 minutes, and then her vision returned to normal. She only partially recalled the event. She had never taken zolpidem before, and she had not had any such disturbances in the past. DISCUSSION: There have been 21 case reports of zolpidem-related psychotic symptoms in the literature; however, the exact mechanism by which zolpidem may cause visual perception changes is undetermined. Many factors have been correlated with zolpidem-induced visual experiences, such as pharmacokinetic factors, gender, age, and hypoalbuminemia. This patient shared certain similarities such as gender, dosage, and time of onset and duration of adverse reactions. CONCLUSIONS: An objective causality assessment revealed that the zolpidem-induced visual perception distortion in this patient was probable. Clinicians should be aware of the potential for visual perception distortion, as this is an uncommon adverse effect.

This study aimed to assess the boundaries of the schizophrenia spectrum and whether inclusion of such phenotypes increases power for linkage analysis of schizophrenia. Participants were 234 first degree relatives (FDRs) of 94 schizophrenia probands in Northern Taiwan who completed a direct interview using the Diagnostic Interview for Genetic Studies (DIGS). Based on best estimate diagnosis, the morbidity risk in the relatives for schizophrenia was 2.5 percent (Weinberg's shorter method) or 3.9 percent (Kaplan-Meier estimate). Depending on the stringency of diagnosis, lifetime prevalence was 2.6 percent to 4.7 percent for schizotypal personality disorder, 3.4 percent to 8.6 percent for paranoid personality disorder, and 1.3 percent to 3.4 percent for schizoid personality disorder. These figures are significantly higher than the corresponding figures in the general population. However, none of the recurrence risk ratio for any spectrum that included both schizophrenia and a personality disorder (3.0 to 5.9) was greater than that of schizophrenia alone (9.3 to 14.4). Thus, including schizophrenia-related personality disorders in the spectrum did not increase power for linkage analysis of schizophrenia.

Association of the gamma-aminobutyric acid A receptor gene cluster with alcohol dependence in Taiwanese Han

The lifetime prevalence rate of major depressive disorder (MDD), as defined by the Chinese Diagnostic Interview Schedule, is 1.14% in Taiwan. This is significantly lower than the lifetime prevalence rates reported in Western studies and similar to other studies in the Chinese population using similar methods for assessing cases of MDD. Epidemiological data from 136 MDD cases were analyzed to provide possible explanations for this difference in lifetime prevalence rates. The low rate of broken families in Chinese culture, low comorbidity rate, and older age of onset of MDD may suggest a reality of low lifetime prevalence rates of MDD in Taiwan.

Schizophrenic patients have been shown to have a moderate excess of winter births in the areas where seasonal variations in weather are large. In this report, we examined the seasonality of schizophrenic births in Taiwan, which has a subtropical climate. Using nationwide hospitalization data (2429 male and 1320 female schizophrenic patients), we applied the life table method to compare the risk of schizophrenia among 12 cohorts of month-of-birth for males and females, respectively. Differences among the risks of the 12 cohorts were tested using the logrank test. The samples were further stratified by family history and age at onset. There was a significant association between the risk of being admitted as a schizophrenic and month of birth for both males and females. The cohorts born in November and January had the highest risks. After stratification, the association was significant only for non-familial, male, and early onset schizophrenic patients. The results indicate that seasonally varying factors might increase the risk of schizophrenia, especially in those without a family history of the disease. Men are more vulnerable to such factors than women, and the schizophrenics resulting from such insults tend to be early onset.