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Abstract Older adults with major depressive disorder (MDD) or early cognitive decline during the subjective cognitive decline (SCD) stage may exhibit neuropsychiatric symptoms such as anxiety, depression, and subtle cognitive impairment. The clinicopathological features and biological mechanisms of MDD differ from those of SCD among older adults; these conditions thus require different treatment strategies. This study enrolled 82 participants above 50 years old with normal cognitive levels from the communities to examine biomarker–behavior correlations between MDD (n = 23) and SCD (n = 23) relative to a normal control (NC) group (n = 36). Multidomain assessments were performed for all participants, including immunomagnetic reduction tests to detect plasma beta-amyloid (Aβ), total tau (Tau), phosphorylated tau-181 (p-Tau181), neurofilament light chain, and glial fibrillary acidic protein (GFAP). This study observed that depressive symptoms in MDD were associated with amyloid pathology (plasma Aβ40 vs. HADS-D: R = 0.45, p = 0.031; Aβ42/Aβ40 vs. HADS-D: R = −0.47, p = 0.024), which was not observed in the NC (group difference p

Abstract Background Subjective cognitive decline (SCD) is an early stage of dementia linked to Alzheimer's disease pathology. White matter changes were found in SCD using diffusion tensor imaging, but there are known limitations in voxel-wise tensor-based methods. Fixel-based analysis (FBA) can help understand changes in white matter fibers and how they relate to neurodegenerative proteins and multidomain behavior data in individuals with SCD. Methods Healthy adults with normal cognition were recruited in the Northeastern Taiwan Community Medicine Research Cohort in 2018–2022 and divided into SCD and normal control (NC). Participants underwent evaluations to assess cognitive abilities, mental states, physical activity levels, and susceptibility to fatigue. Neurodegenerative proteins were measured using an immunomagnetic reduction technique. Multi-shell diffusion MRI data were collected and analyzed using whole-brain FBA, comparing results between groups and correlating them with multidomain assessments. Results The final enrollment included 33 SCD and 46 NC participants, with no significant differences in age, sex, or education between the groups. SCD had a greater fiber-bundle cross-section than NC (pFWE

Persons who have experienced traumatic brain injury (TBI) may encounter a range of changes in their physical, mental, and cognitive functions as well as high fatigue levels. To gain a comprehensive understanding of the challenges faced by persons after TBI, we conducted multi-domain assessments among community-dwelling persons with a history of TBI and compared them with age- and sex-matched controls from the Northeastern Taiwan Community Medicine Research Cohort between 2019 and 2021. A total of 168 persons with TBI and 672 non-TBI controls were not different in terms of demographics, comorbidities, and physiological features. However, compared with the non-TBI group, the TBI group had a distinct lifestyle that involved increased reliance on analgesics (6.9% vs. 15.0%, respectively; p?=?0.001) and sleep aids (p?=?0.008), which negatively affected their quality of life. Moreover, they consumed more coffee (p?0.001), tea (p?

Background: Flipped classroom (FC) style Australian faculty development program Teaching on the Run (TOTR) was introduced into Chang Gung Memorial Hospital since 2014. However, its effectiveness in Taiwan has not been formally assessed. This work intended to examine the learning gain of TOTR and identify the moderators of FC outcome by using TOTR as a representative model of FC. Methods: A non-controlled before-after study was undertaken by retrospective analysis of learning data collected during TOTR workshop. Multiple choice questions were tested at baseline (pre-test), after pre-class learning (mid-test) and after classroom activity (post-test) to assess the learning gain. All available demographic and learning variables were included in the moderator analysis. Results: Stepwise and significant improvement in exam scores was noted from pre-test to mid-test and post-test (p

Abstract Chronic ketamine abuse is associated with bladder dysfunction and cystitis. However, the effects of ketamine abuse on the urinary proteome profile and the correlations among urinary proteins, urinary ketamine (and metabolites) and clinicopathological features of ketamine-induced bladder dysfunction remain to be established. Here, we recruited 56 ketamine abusers (KA) and 40 age-matched healthy controls (HC) and applied the iTRAQ-based proteomics approach to unravel quantitative changes in the urine proteome profile between the two groups. Many of the differentially regulated proteins are involved in the complement and coagulation cascades and/or fibrotic disease. Among them, a significant increase in APOA1 levels in KA relative to control samples (392.1 ± 59.9 ng/ml vs. 13.7 ± 32.6 ng/ml, p

BackgroundSubjective cognitive decline (SCD) appears in the preclinical stage of the Alzheimer's disease continuum. In this stage, dynamic features are more sensitive than static features to reflect early subtle changes in functional brain connectivity. Therefore, we studied local and extended dynamic connectivity of the resting brain of people with SCD to determine their intrinsic brain changes.MethodsWe enrolled cognitively normal older adults from the communities and divided them into SCD and normal control (NC) groups. We used mean dynamic amplitude of low-frequency fluctuation (mdALFF) to evaluate region of interest (ROI)-wise local dynamic connectivity of resting-state functional MRI. The dynamic functional connectivity (dFC) between ROIs was tested by whole-brain-based statistics.ResultsWhen comparing SCD (N = 40) with NC (N = 45), mdALFFmean decreased at right inferior parietal lobule (IPL) of the frontoparietal network (FPN). Still, it increased at the right middle temporal gyrus (MTG) of the ventral attention network (VAN) and right calcarine of the visual network (VIS). Also, the mdALFFvar (variance) increased at the left superior temporal gyrus of AUD, right MTG of VAN, right globus pallidum of the cingulo-opercular network (CON), and right lingual gyrus of VIS. Furthermore, mdALFFmean at right IPL of FPN are correlated negatively with subjective complaints and positively with objective cognitive performance. In the dFC seeded from the ROIs with local mdALFF group differences, SCD showed a generally lower dFCmean and higher dFCvar (variance) to other regions of the brain. These weakened and unstable functional connectivity appeared among FPN, CON, the default mode network, and the salience network, the large-scale networks of the triple network model for organizing neural resource allocations.ConclusionThe local dynamic connectivity of SCD decreased in brain regions of cognitive executive control. Meanwhile, compensatory visual efforts and bottom-up attention rose. Mixed decrease and compensatory increase of dynamics of intrinsic brain activity suggest the transitional nature of SCD. The FPN local dynamics balance subjective and objective cognition and maintain cognitive preservation in preclinical dementia. Aberrant triple network model features the dFC alternations of SCD. Finally, the right lateralization phenomenon emerged early in the dementia continuum and affected local dynamic connectivity.

Objective: Although previous studies postulated that physical and cognitive decline codeveloped in preclinical dementia, the interconnected relationship among subjective cognitive complaints (SCCs), objective cognitive performance, and physical activity remained hazy. We investigated the mediating roles of physical activity between subjective and objective cognition. Diffusion tensor imaging (DTI) was utilized to test our hypothesis that brain white matter microstructural changes underlie the physical-cognitive decline in subjective cognitive decline (SCD).Methods: We enrolled cognitively normal older adults aged > 50 years in the Community Medicine Research Center of Keelung Chang Gung Memorial Hospital during 2017–2020. Regression models analyzed mediation effects of physical activity between subjective and objective cognition. The self-reported AD8 questionnaire assessed SCCs. The SCD group, defined by AD8 score ≥ 2, further underwent diffusion MRI scans. Those who agreed to record actigraphy also wore the SOMNOwatch™ for 72 h. Spearman's correlation coefficients evaluated the associations of diffusion indices with physical activity and cognitive performance.Results: In 95 cognitively normal older adults, the AD8 score and the Montreal Cognitive Assessment (MoCA) score were mediated partially by the metabolic equivalent of the International Physical Activity Questionnaire-Short Form (IPAQ-SF MET) and fully by the sarcopenia score SARC-F. That is, the relation between SCCs and poorer cognitive performance was mediated by physical inactivity. The DTI analysis of 31 SCD participants found that the MoCA score correlated with mean diffusivity at bilateral inferior cerebellar peduncles and the pyramids segment of right corticospinal tract [p < 0.05, false discovery rate (FDR) corrected]. The IPAQ-SF MET was associated with fractional anisotropy (FA) at the right posterior corona radiata (PCR) (p < 0.05, FDR corrected). In 15 SCD participants who completed actigraphy recording, the patterns of physical activity in terms of intradaily variability and interdaily stability highly correlated with FA of bilateral PCR and left superior corona radiata (p < 0.05, FDR corrected).Conclusions: This study addressed the role of physical activity in preclinical dementia. Physical inactivity mediated the relation between higher SCCs and poorer cognitive performance. The degeneration of specific white matter tracts underlay the co-development process of physical-cognitive decline in SCD.

Background: Subjective cognitive decline (SCD) is one of the early warning signs of objective cognition impairment and dementia. Methods: This cross-sectional study screened SCD and studied multiple domains of mental health, lifestyle, and life quality of the community-dwelling people in the northern coastal region of Taiwan. Results: Among 426 valid AD8 questionnaires, a cutoff of score 2 divided subjects into 115 with SCD (SCD+) and 311 without SCD (SCD–). Analysis of age, sex, body compositions, and blood tests revealed an older age (60.7 ± 10.9 years) of the SCD+ group than the SCD– group (57.6 ± 12.0 years, p < 0.05). Further exclusion of subjects younger than 50 years eliminated age differences and left 100 with SCD (SCD+_50) and 229 without (SCD–_50). Multidomain comparisons of the SCD+_50 group over the SCD–_50 group were made: the Taiwanese Depression Questionnaire found a higher likelihood of depression; the Pittsburgh Sleep Quality Index revealed suboptimal sleep quality; the SF-36 showed inferior function of all 8 aspects of quality of life; the Health-Promoting Lifestyle Profile documented a less health-seeking lifestyle of nutrition, self-actualization, and stress management. Conclusions: Aging increased the SCD risk. People with SCD had suboptimal performance in mental health and life quality in addition to subjective cognition problems.

Excessive alcohol consumption, as part of an unhealthy lifestyle, can contribute to metabolic abnormalities. This study investigated the sex differences in the relationship between excessive drinking and the risk of metabolic abnormalities. This community-based study included 3387 participants (age range: 30–103 years, mean age ± SD: 57 ± 13.5 years, 38.2% males) from the northeastern region of Taiwan. All participants completed a demographic survey and were subjected to blood tests. The risks of excessive drinking were evaluated using the Alcohol Use Disorder Identification Test (AUDIT). The results showed that males were at higher risks of obesity, hypertension, and hypertriglyceridemia, but at a lower risk of abdominal obesity than females. Males with hazardous drinking were at greater risks of hypertension, hyperglycemia, low serum levels of high-density lipoprotein cholesterol, and hypertriglyceridemia compared to those with no drinking. Females with hazardous drinking were at a greater risk of hypertension than those with no drinking. There was no interaction effect of sex and excessive drinking on the risks of metabolic abnormalities after controlling for demographics and lifestyle-related habits. Future studies are warranted to explore the sex-specific risk factors for metabolic abnormalities and to elucidate the mechanism underlying this association between alcohol consumption and metabolic abnormalities.

Major depressive disorder (MDD) is a global healthcare issue and one of the leading causes of disability. Machine learning combined with non-invasive electroencephalography (EEG) has recently been shown to have the potential to diagnose MDD. However, most of these studies analyzed small samples of participants recruited from a single source, raising serious concerns about the generalizability of these results in clinical practice. Thus, it has become critical to re-evaluate the efficacy of various common EEG features for MDD detection across large and diverse datasets. To address this issue, we collected resting-state EEG data from 400 participants across four medical centers and tested classification performance of four common EEG features: band power (BP), coherence, Higuchi’s fractal dimension, and Katz’s fractal dimension. Then, a sequential backward selection (SBS) method was used to determine the optimal subset. To overcome the large data variability due to an increased data size and multi-site EEG recordings, we introduced the conformal kernel (CK) transformation to further improve the MDD as compared with the healthy control (HC) classification performance of support vector machine (SVM). The results show that (1) coherence features account for 98% of the optimal feature subset; (2) the CK-SVM outperforms other classifiers such as K-nearest neighbors (K-NN), linear discriminant analysis (LDA), and SVM; (3) the combination of the optimal feature subset and CK-SVM achieves a high five-fold cross-validation accuracy of 91.07% on the training set (140 MDD and 140 HC) and 84.16% on the independent test set (60 MDD and 60 HC). The current results suggest that the coherence-based connectivity is a more reliable feature for achieving high and generalizable MDD detection performance in real-life clinical practice.

Background: Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is a common drug of abuse worldwide. Existing evidence suggest a disruption of oxytocin system involves in the development of addiction. In this study, we aimed to investigate the role of oxytocin in ketamine addiction by measuring the blood oxytocin levels in ketamine-dependent (KD) patients.Methods: Sixty-five KD patients and 65 controls were enrolled. Fasting plasma levels of oxytocin were determined at baseline and 1 and 2 weeks after ketamine withdrawal. Ketamine use variables, Beck Depression Inventory, Beck Anxiety Inventory (BAI), Visual Analog Scale for craving, and Childhood Trauma Questionnaire-short form were assessed in KD patients.Results: KD patients had significantly lower levels of oxytocin at baseline compared to controls (5.89 ± 2.13 vs. 9.53 ± 4.17 ng/mL, P < 0.001). Oxytocin levels increased after one (6.74 ± 2.63, P < 0.002) and 2 weeks (6.89 ± 2.69, P = 0.01) of withdrawal in KD patient despite the levels were still lower than controls (P = 0.001 and 0.002, respectively). The clinical variables did not correlate with baseline oxytocin levels except BAI scores, which showed a negative correlation with the levels (r = −0.263; P = 0.039).Conclusion: We found a distinctively reduced oxytocin level in KD patients and the level did not normalize after early abstinence. Lower oxytocin might be associated with anxious phenotype of ketamine dependence. These results suggest that oxytocin system dysregulated following chronic ketamine abuse and might provide insight in evaluating the potential therapeutic use of oxytocin for treating ketamine dependence.

Background Genetic variants and medication adherence have been identified to be the main factors contributing to lithium treatment response in bipolar disorders. Aims To simultaneously examine effects of variant glutamate decarboxylase-like protein 1 (GADL1) and medication adherence on response to lithium maintenance treatment in Han Chinese patients with bipolar I (BPI) disorder. Method Frequencies of manic and depressive episodes between carriers and non-carriers of the effective GADL1 rs17026688 T allele during the cumulative periods of off-lithium, poor adherence to lithium treatment and good adherence to lithium treatment were compared in Han Chinese patients with BPI disorder (n = 215). Results GADL1 rs17026688 T carriers had significantly lower frequencies of recurrent affective episodes than non-T carriers during the cumulative period of good adherence, but not during those of poor adherence. Conclusions GADL1 rs17026688 and medication adherence jointly predict response to lithium maintenance treatment in Han Chinese BPI patients.

A 2-week, randomized, parallel-group open trial was designed to evaluate the safety and tolerability of a rapid initiation regimen with a higher dose of quetiapine (up to 800 mg/d by Day 4) than that used in the conventional initiation regimen of quetiapine (up to 400 mg/d by Day 5) in patients with schizophrenia or schizoaffective disorders. Forty patients were recruited and randomly (3:1) assigned to either the group with rapid initiation of quetiapine or the group with conventional initiation. At the end of the investigation, the difference between the groups in the incidence of adverse events was not significant; a significant drop in the Barnes Akathisia Rating Scale and Simpson-Angus Scale scores was observed only in the group with the rapid initiation regimen. The groups did not differ in terms of improvement on the Clinical Global Impression—Severity of Illness and Positive and Negative Syndrome Scale at the end of the study. The results of our 2-week study suggest that rapid initiation with a higher dose of quetiapine (up to 800 mg/d by Day 4) is well tolerated in patients with schizophrenia or schizoaffective disorders and does not compromise efficacy relative to the conventional initiation.

Cardiovascular disease is the leading cause of mortality in hemodialysis patients and is associated with chronic inflammation. Elevation of uremic toxins, particular protein-bound uremic toxins, is a possible cause of hyper-inflammation in hemodialysis patients. But the association between uremic toxins and inflammatory markers in hemodialysis is still unclear.We conducted a cross-sectional study to evaluate the association of the serum uremic toxins and inflammatory markers in hemodialysis patients.The uremic toxins were not associated with inflammatory markers--including high sensitivity C-reactive protein, IL(Interleukin) -1β, IL-6, tumor necrosis factor-α. In multiple linear regression, serum levels of total p-cresol sulfate (PCS) were independently significantly associated with serum total indoxyl sulfate (IS) (standardized coefficient: 0.274, p

Objective: The Brief Assessment of Cognition in Schizophrenia (BACS) is a cognitive assessment tool used to measure the broad aspects of cognition that are most frequently impaired in patients with schizophrenia. This study aims to develop the normative data of the Chinese version of the BACS among the Mandarin-speaking population. Method: This cross-sectional study included 382 healthy participants (age range: 19-79 years; mean age: 48.0 ± 16.7 years, 47.6% men) in Taiwan, who were evaluated with the BACS. Means and standard deviations of subtests and composite scores were arranged by age group and gender. The Z-scores calculated based on the U.S. norms were compared to our scores based on the norms established in this study. Results: The raw scores of all the BACS tests (verbal memory, digit sequencing, token motor test, verbal fluency, symbol coding, and Tower of London) were negatively correlated with participants' age. Women were superior to men in verbal memory, but inferior to them in executive function. Furthermore, applying the U.S. norms of the BACS to determine the performance of the Chinese BACS results in bias with regard to verbal memory, token motor test, verbal fluency, symbol coding, Tower of London and composite score. Conclusions: These findings demonstrate that directly applying western cognitive norms to a Mandarin-speaking population can cause biased interpretations. The results of this study can be an important reference for clinical settings and research related to cognitive assessments in Mandarin-speaking Chinese populations. [ABSTRACT FROM AUTHOR]

Background: This study investigates differences in depression and anxiety between patients with chronic hepatitis C who are treated with peginterferon alpha-2a (PegIFN-a-2a) plus ribavirin and those who are treated with peginterferon alpha-2b (PegIFN-a-2b) plus ribavirin. Methods: In this 24 week, non-randomized, observational, prospective study, 55 patients with chronic hepatitis C were treated with PegIFN-α-2a plus ribavirin (Group 1), and 26 patients were treated with PegIFN-α-2b plus ribavirin (Group 2). All patients underwent assessment using the Hospital Anxiety and Depression Scale (HADS) at the baseline and at weeks 4, 12 and 24. Patients with depression scores (HADS-D) = 8 and anxiety scores (HADS-A) = 8 were defined as having depression and anxiety, respectively. The factors that were associated with depression and anxiety during the 24 week antiviral treatment were determined. Results: During the 24 week antiviral treatment, the proportion of patients with depression significantly increased over time in both groups (Group 1: p = 0.048; Group 2: p = 0.044). The proportion of patients with anxiety did not significantly change during the follow-up period in either group. Incidences of depression or anxiety did not differ significantly between Group 1 and Group 2. A history of alcohol use disorder was an independent predictor of depression at week 12 (p < 0.001) and week 24 (p < 0.001), and a poor virological response to treatment was associated with depression at week 24 (p = 0.029). Patients who had more physical comorbidities were more likely to suffer from anxiety at week 12 (p = 0.038). Conclusions: This study did not identify significant differences in depression or anxiety between in patients with chronic hepatitis C who underwent a 24 week antiviral treatment regimen with PegIFN-α-2a plus ribavirin and those who underwent a regiment with PegIFN-α-2b plus ribavirin. Future research with larger samples and a randomized, controlled design are required to verify the findings in this study. [ABSTRACT FROM AUTHOR]

Objective: A test battery that measures cognitive function impairment in patients with schizophrenia, the Brief Assessment of Cognition in Schizophrenia (BACS), has been translated into various languages and validated. This study aimed to test the reliability and validity of the Chinese version of the BACS in a Chinese-speaking population. Methods: All participants in this study (66 patients with schizophrenia [mean age: 41.2 years, 57.6% male] and 66 age- and sex-matched healthy controls) were from Taiwan and assessed using the BACS and the University of California, San Diego (UCSD) Performance-Based Skills Assessment, Brief Version (UPSA-B). Thirty-eight of the 66 patients with schizophrenia received a reassessment using the BACS. Results: The BACS had good test-retest reliability, and all BACS subtests had statistically insignificant practice effects. Principal components analysis demonstrated that a one-factor solution best fits our dataset (60.9% of the variance). In both patients and controls, the BACS composite scores were positively correlated with all BACS subscales (P,0.001) and UPSA-B scales (P,0.001). Furthermore, all BACS subtests (verbal memory, working memory, motor speed, verbal fluency, attention and processing speed, and executive function) significantly differentiated patients with schizophrenia from healthy controls (P,0.001), and the BACS composite score had the best discriminative validity (P,0.001). Conclusion: The Chinese version of the BACS exhibits satisfactory psychometric properties, including high test-retest reliability, high internal consistency, acceptable concurrent validity, and good discriminant validity. We suggest that the BACS is a reliable and practical tool for assessing cognitive function in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: Depression is the most prevalent comorbid psychiatric disease among hemodialysis patients with end-stage renal disease. This cross-sectional study investigated whether depression in hemodialysis patients is associated with the polymorphism of the 5' flanking transcriptional region (5-HTTLPR) of the serotonin transporter gene, the valine (Val)-to-methionine (Met) substitution at codon 66 (Val66Met) polymorphism of the brain-derived neurotrophic factor (BDNF) gene, or plasma BDNF levels. Methods: A total of 188 participants (mean age: 58.5±14.0 years; 89 men and 99 women) receiving hemodialysis at the Chang Gung Memorial Hospital were recruited. The diagnosis of major depressive disorder (MDD) was confirmed using the Chinese version of the Mini International Neuropsychiatric Interview. The genotypes of 5-HTTLPR and BDNF Val66Met were conducted using polymerase chain reactions plus restriction fragment length polymorphism analysis. The plasma BDNF levels were measured using an enzyme-linked immunosorbent assay kit. Results: Forty-five (23.9%) patients fulfilled the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) criteria for a MDD. There were no significant effects of the 5-HTTLPR or BDNF Val66Met gene polymorphism on MDD among the hemodialysis patients. The plasma BDNF levels correlated significantly with age (P=0.003) and sex (P=0.047) but not with depression, the genotypes of 5-HTTLPR and BDNF Val66Met, the current antidepressant treatment, or the duration under hemodialysis. Conclusion: Our results did not support the hypothesis of an involvement of the 5HTTLPR and BDNF Val66Met genotypes, or plasma BDNF levels in the pathogenesis of depression, in patients receiving hemodialysis. A study with a large sample size and homogenous patient group is warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: Suicide is a major public health concern. This study aimed to determine the predictors of repeated suicide attempts, focusing on whether lethality level of the suicidal method predicts the risk of subsequent suicide attempts. Methods: All consecutive individuals (N=2,070) with an episode of nonfatal self-harm registered in a surveillance database provided by the Department of Health of Keelung City Government in Taiwan from January 1, 2006 to December 31, 2010 were enrolled and followed up until the end of 2011. The earliest attempt recorded in the database was defined as the index attempt. Subjects were classified according to suicide method into low-lethal and high-lethal groups. Data on time of and methods chosen for subsequent suicide attempts during the follow-up period were analyzed. Results: Of the total people screened for the study, 18.1% made a repeated suicide attempt. Subjects in the high-lethal group were more likely to be male; aged 35-64 years; and single, divorced, or widowed. Compared to other time intervals, most subsequent suicide attempts occurred within 6 months from the index attempt. The independent predictors for repeated suicide attempts were the use of low-lethal methods in the index attempt and being 35-49 years old. Using high-lethal methods and being older than 50 years were associated with changing suicide method for the second attempt. Conclusion: Lethality level of former suicidal method could predict repeated suicide attempts and changing of suicide methods. Further clarification is needed on whether a higher risk of repeat attempts is associated with higher rates of suicide mortality. [ABSTRACT FROM AUTHOR]

Objectives: Use of anxiolytics-hypnotics, including benzodiazepines and "z" hypnotics, is a public health concern. This study aimed to investigate the trends in prevalence of anxiolytic-hypnotic drug use and polypharmacy (simultaneous use of two or more anxiolytics-hypnotics) in Taiwan. Methods: A dynamic sample of one million individuals who were randomly selected from the National Health Insurance database was used to detect populationwide trends in the use of anxiolytics-hypnotics in Taiwan between 2002 and 2009. The analyses included drugs that are administered orally, intravenously, or intramuscularly as well as single or compound drugs. The authors identified the number of individuals who used the drugs, the sum of days of reported drug use for all individuals (person-days), and the distribution of anxiolytic-hypnotic polypharmacy for all claims for ambulatory, pharmacy, and hospital care. Results: Annual prevalence of any anxiolytic-hypnotic use in Taiwan was higher than 20%. The number of person-days greatly increased from 2002 (4.0%) to 2009 (6.6%). The increases in use between 2002 and 2009 were greatest for clonazepam (prevalence, 7% versus 1.8%; person-days, .2% versus .6%) and zolpidem (prevalence, 2.4% versus 4.2%; person-days, .5% versus 1.5%). Polypharmacy accounted for almost 70% of all person-days of anxiolytic-hypnotic use. Conclusions: This nationwide, population-based survey presents real-world epidemiological evidence about anxiolytic- hypnotic use. The adverse effects of the long-term use of anxiolytics- hypnotics have been established, and unnecessary use of these drugs, particularly in polypharmacy regimens, should be avoided. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies (GWAS) have been conducted on many psychiatric disorders. Evidence from large GWAS indicates that the single nucleotide polymorphism (SNP) rs1344706 in the zinc-finger protein 804A gene (ZNF804A) is associated with psychotic disorders including bipolar disorder and schizophrenia. One study also found significant association between rs1344706 and the executive control network of attention. In this study we examine the role of the rs1344706 polymorphism that previously showed association with BD and is known to alter expression of the gene in two clinical family-based ADHD samples from the UK and Taiwan. Findings: To investigate the association between rs1344706 and ADHD, two family samples of ADHD probands from the United Kingdom (n = 180) and Taiwan (n = 212) were genotyped using TaqMan SNP genotyping assays and analysed using within-family transmission disequilibrium test. No significant associations were found between rs1344706 polymorphism and ADHD in either of the samples from Taiwan (P = 0.91) and UK (P = 0.41). Even combining the two datasets together the A allele of rs1344706 SNP was still not significantly over-transmitted to affected probands (P = 0.50). Furthermore, there was no evidence of association with the specific symptoms subgroups of inattention or hyperactivity-impulsivity. Conclusions: In this study we used family-based ADHD data in the UK and Taiwanese population to test for an association between rs1344706 SNP in the ZNF804A gene and ADHD. Results showed no significant association of rs1344706 with ADHD in UK and Taiwanese samples. [ABSTRACT FROM AUTHOR]

Objective: Hemodialysis has an adverse impact on the immunological, nutritional, and emotional status of patients. The biochemical markers of inflammation and nutrition were studied as well as the relationship of these factors to emotional symptoms. Method: One hundred and ninety-five patients undergoing hemodialysis were enrolled. The mean age was 58.5 years. Emotional symptoms were assessed using the Mini International Neuropsychiatric Interview, Hospital Anxiety and Depression Scale, Chalder Fatigue Scale, and Short-form Health-related Quality of Life. Venus blood was collected for laboratory assessment of serum hemoglobin, albumin, ferritin, C-reactive protein, interleukin (IL) 1(3), IL-6, and tumor necrosis factor a. Results: Among the 195 subjects (92 men and 103 women), 47 (24.1%) fulfilled the criteria for a major depressive disorder (MDD). The IL-6 level in patients with a MDD was significantly higher than in the patients without a MDD. Significant correlation was observed among the following factors: IL-6, fatigue, and quality of life for both physical and mental components. The albumin levels showed a significant correlation with the IL-6 and depression scores. Conclusions: These results show that the serum levels of albumin and IL-6 might be laboratory markers associated with the expression of emotional symptoms in patients undergoing hemodialysis. Prospective studies are needed to determine the causal relationships among these variables. [ABSTRACT FROM AUTHOR]

Background: Comorbid anxiety symptoms,in patients with a primary anxiety disorder or a mood disorder, leads to poor patient outcomes and burdens the healthcare system. This pilot study evaluated the feasibility of extended-release quetiapine fumarate (quetiapine XR) for the treatment of patients with either a primary anxiety disorder or a mood disorder with comorbid anxiety symptoms compared to a placebo, as an adjunct to antidepressant therapy. Methods: Thirty-nine patients with a diagnosis of a primary anxiety disorder or a mood disorder with comorbid anxiety symptoms were enrolled in this study. Patients with a stable dose of antidepressant therapy were randomized according to a 2:1 probability of receiving either quetiapine XR or a placebo adjunctive treatment for 8 weeks. The efficacy was assessed by the Hamilton Anxiety Rating Scale (HAM-A) and the Clinical Global Impression of severity (CGI-S) score at baseline, week 1, 4, and 8. Results: A total of 35 patients were included in this intention-to treat (ITT) population for the efficacy analysis (quetiapine XR: 22 patients; placebo: 13 patients). At week 4, statistically significant differences were observed on both the HAM-A score (p = 0.003) and the CGI-S score (p = 0.025), favouring the quetiapine XR (-13.00 ± 4.14) compared to placebo (-6.63 ± 5.42). However, no statistically significant difference was observed between the two groups with regard to changes from the baseline to week 8 on the HAM-A score (p = 0.332) or the CGI-S score (p = 0.833). Conclusions: Augmentation of antidepressant treatment with quetiapine XR did not result in clinical improvement according to the outcome measure of anxiety using the HAM-A and CGI-S scores at week 8, among the patients with either a primary anxiety disorder or a mood disorder with comorbid anxiety symptoms. However, treatment with quetiapine XR as an adjunct to antidepressant therapy appeared to provide a short-term benefit at 4 weeks. Further study is needed with a larger sample size, randomized controlled design and control of the dosage prescribed. Trial registration: Clinicaltrials.gov identifier: NCT00912535 [ABSTRACT FROM AUTHOR]

Background: Methylphenidate (MPH), a psycho-stimulant, is the most widely administered drug for the pharmacological management of patients with attention deficit hyperactivity disorder (ADHD). This study attempts to determine whether sustainable improvements occur in neurocognitive function among ADHD patients following 12-month treatment with MPH, at drug-free status. Whether age groups, gender or ADHD subtypes differ in neurocognitive performance during MPH treatment is also examined. Methods: Study participants consisted of 103 ADHD patients (mean age: 9.1 ± 1.9 years old) who were drug naïve or drug free for at least 6 months. The patients were prescribed oral short-acting MPH at each dose range of 0.3-1.0 mg/kg daily. During 12 months of the study, the patients underwent the test of variables of attention (TOVA) at the baseline, month 6 and month12. Patients were instructed to not intake MPH for one week before the second and the third TOVA. Results: Seventy five patients completed the study. Results of this study indicated that although commission errors and response sensitivity (d') significantly improved during MPH treatment for 12 months, omission errors, response time, response time variability and ADHD score did not. While younger ADHD patients (<9 y/o) performed better in response time, response time variability, d' and ADHD score than older ones (≥9 y/o), the latter more significantly improved in response time than the former during 12 months of treatment. Additionally, boys improved more than girls in omission error and d'. Moreover, although ADHD subtypes significantly differed in ADHD score during the treatment, MPH treatment and ADHD subtypes did not interact with each other for all TOVA indices. Conclusions: ADHD patients significantly improved in impulsivity and perceptual sensitivity, determined as TOVA, during MPH treatment for 12 months. Age and gender, yet not ADHD subtypes, appear to influence the MPH treatment effects in some indices of TOVA. A future study containing a comparison group is suggested to confirm whether the neurocognitive improvements are attributed to long-term effects of MPH or natural maturation of patients. [ABSTRACT FROM AUTHOR]

The article discusses the levels of job stress, depression and job related diseases among physicians of hospitals in Taiwan. The data was collected regarding health related hazards caused due to occupation among physicians with the help of questionnaires. According to the results provided by the authors, level of depression was higher in physicians than common people and higher depression rate was found in the individuals who were alcoholics. The depression level was low in Eastern Taiwan.

Background: The aims of this study were to determine the time course of improvements in attention deficit hyperactivity disorder (ADHD) clinical symptoms and neurocognitive function in a realistic clinical setting, and the differences in ADHD symptom improvement using different classifications of ADHD subtypes. Methods: The Child Behavior Checklist (CBCL) was completed by parents of ADHD children at the initial visit. The computerized Continuous Performance Test (CPT), Swanson, Nolan, and Pelham, and Version IV Scale for ADHD (SNAP-IV), and ADHD Rating Scale (ADHD-RS) were performed at baseline, one month, three months, and six months later, respectively. Patient care including drug therapy was performed at the discretion of the psychiatrist. The ADHD patients were divided into DSM-IV subtypes (Inattentive, Hyperactive-impulsive and Combined type), and were additionally categorized into aggressive and non-aggressive subtypes by aggression scale in CBCL for comparisons. Results: There were 50 ADHD patients with a mean age of 7.84 ± 1.64 years; 15 of them were inattentive type, 11 were hyperactive-impulsive type, and 24 were combined type. In addition, 28 of the ADHD patients were grouped into aggressive and 22 into non-aggressive subtypes. There were significant improvements in clinical symptoms of hyperactivity and inattention, and impulsivity performance in CPT during the 6-month treatment. The clinical hyperactive symptoms were significantly different between ADHD patients sub-grouping both by DSM-IV and aggression. Non-aggressive patients had significantly greater changes in distraction and impulsivity performances in CPT from baseline to month 6 than aggressive patients. Conclusions: We found that ADHD symptoms, which included impulsive performances in CPT and clinical inattention and hyperactivity dimensions, had improved significantly over 6 months under pragmatic treatments. The non-aggressive ADHD patients might have a higher potential for improving in CPT performance than aggressive ones. However, it warrant further investigation whether the different classifications of ADHD patients could be valid for predicting the improvements in ADHD patients' clinical symptoms and neurocognitive performance. [ABSTRACT FROM AUTHOR]

Background: The circadian locomotor output cycles kaput (CLOCK) gene encodes protein regulation circadian rhythm and also plays some roles in neural transmitter systems including the dopamine system. Several lines of evidence implicate a relationship between attention-deficit hyperactivity disorder (ADHD), circadian rythmicity and sleeping disturbances. A recent study has reported that a polymorphism (rs1801260) at the 3'-untranslated region of the CLOCK gene is associated with adult ADHD. Methods: To investigate the association between the polymorphism (rs1801260) in ADHD, two samples of ADHD probands from the United Kingdom (n = 180) and Taiwan (n = 212) were genotyped and analysed using withinfamily transmission disequilibrium test (TDT). Bonferroni correction procedures were used to just for multiple comparisons. Results: We found evidence of increased transmission of the T allele of the rs1801260 polymorphism in Taiwanese samples (P = 0.010). There was also evidence of preferential transmission of the T allele of the rs1801260 polymorphism in combined samples from the Taiwan and UK (P = 0.008). Conclusion: This study provides evidence for the possible involvement of CLOCK in susceptibility to ADHD. [ABSTRACT FROM AUTHOR]

Background: Attention deficit hyperactivity disorder (ADHD) is a complex neurobehavioral disorder. The dopamine transporter gene (DAT1/SLC6A3) has been considered a good candidate for ADHD. Most association studies with ADHD have investigated the 40-base-pair variable number of tandem repeat (VNTR) polymorphism in the 3'-untranslated region of DAT1. Only few studies have reported association between promoter polymorphisms of the gene and ADHD. Methods: To investigate the association between the polymorphisms -67A/T (rs2975226) and - 839C/T (rs2652511) in promoter region of DAT1 in ADHD, two samples of ADHD patients from the UK (n = 197) and Taiwan (n = 212) were genotyped, and analysed using within-family transmission disequilibrium test (TDT). Results: A significant association was found between the T allele of promoter polymorphism -67A/ T and ADHD in the Taiwanese population (P = 0.001). There was also evidence of preferential transmission of the T allele of -67A/T polymorphism in combined samples from the UK and Taiwan (P = 0.003). No association was detected between the -839C/T polymorphism and ADHD in either of the two populations. Conclusion: The finding suggests that genetic variation in the promoter region of DAT1 may be a risk factor in the development of ADHD. [ABSTRACT FROM AUTHOR]

Background: Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable disorder of childhood characterized by inattention, hyperactivity and impulsivity. Molecular genetic and pharmacological studies suggest the involvement of the dopaminergic, serotonergic and noradrenergic neurotransmitter systems in the pathogenesis of ADHD. Monoamine oxidase A (MAO-A) encodes an enzyme that degrades biogenic amines, including neurotransmitters such as norepinephrine, dopamine and serotonin. In this study we examined a 30 bp promoter variable number tandem repeat (VNTR) and a functional G/T single nucleotide polymorphism (SNP) at position 941 in exon 8 (941G/T) of MAO-A for association with ADHD in a Taiwanese sample of 212 ADHD probands. Methods: Within-family transmission disequilibrium test (TDT) was used to analyse association of MAO-A polymorphisms with ADHD in a Taiwanese population. Results: A nominally significant association was found between the G-allele of 941G/T in MAO-A and ADHD (TDT: P = 0.034. OR = 1.57). Haplotype analysis identified increased transmission of a haplotype consisting of the 3-repeat allele of the promoter VNTR and the G-allele of the 941G/T SNP (P = 0.045) to ADHD cases which the strong association with the G-allele drove. Conclusion: These findings suggest the importance of the 941G/T MAO-A polymorphism in the development of ADHD in the Taiwanese population. These results replicate previously published findings in a Caucasian sample. [ABSTRACT FROM AUTHOR]

The article cites a study which investigated the association between dopamine transporter gene (DAT1) and attention-deficit/hyperactivity disorder (ADHD). This disease is considered as a common heritable childhood behavioral disorder. The gene-environment interaction between DAT1 and maternal use of alcohol and tobacco during pregnancy was also examined. The objective of this study was to identify the gene responsible for ADHD.

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent and highly heritable childhood disorder. The dopamine D4 receptor (DRD4) gene has shown a genetic association with ADHD in Caucasian populations with meta-analysis indicating a small but significant effect across datasets. It remains uncertain whether this association can be generalised to non-Caucasian ethnic groups. Here we investigate two markers within the DRD4 gene in a Taiwanese population, the exon 3 variable number tandem repeat (VNTR) and a 5' 120 base-pair duplication. Methods: Within-family transmission disequilibrium tests of association of the 5' 120 base-pair duplication, and exon 3 VNTR in a Taiwanese population. Results: No evidence of association of ADHD with either polymorphism in this population was observed. Conclusion: The DRD4 gene markers investigated were not found to be associated with ADHD in this Taiwanese sample. Further work in Taiwanese and other Asian populations will therefore be required to establish whether the reports of association of DRD4 genetic variants in Caucasian samples can be generalised to Asian populations. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Substance use disorders are familial, and genetic factors explain a substantial degree of their familial aggregation. This study employs an association approach to examine the genetic underpinning of methamphetamine (MAMP) use and MAMP-induced psychosis. METHODS: A total of 416 MAMP abusers from a hospital and a detention center in Taipei were interviewed with the Diagnostic Interview for Genetic Study and the Family Interview for Genetic Study. Genetic polymorphisms of D2-like dopamine receptor genes, DRD2 TaqI A, DRD3 Ser-9-Gly, and DRD4 exon III variable number of tandem repeats, were compared between: (a) MAMP users as a whole and 435 normal controls, and (b) those 154 individuals with MAMP-induced psychosis and the 252 MAMP users with no psychosis. RESULTS: None of the three markers we studied were associated with predisposition to psychosis among the MAMP abusers. The MAMP abusers had a higher (P=0.011) prevalence of the seven-repeat allele of DRD4 than normal controls. CONCLUSIONS: Chance fluctuations in the frequency of rare alleles and ascertainment differences in the case and control samples cannot be ruled out. Therefore, further studies of the seven-repeat allele in MAMP abusers and controls should be performed before an association can be established. [ABSTRACT FROM AUTHOR]

The “Genetics and pharmacogenetics of substance use disorder” session was chaired by Dr Pao-Luh Tao and had three speakers. The speakers and topics were as follows. Dr Li-Shiun Chen discussed “Genomics and personalized medicine for smoking cessation treatments”. Dr Chih-Ken Chen presented a talk on the “Genetics of methamphetamine abuse and methamphetamine psychosis”. Dr Yu-Li Liu described a “Pharmacogenomics study in a Taiwan methadone maintenance cohort”. [ABSTRACT FROM AUTHOR]