Papers by Tzung-Jeng Hwang
International Psychogeriatrics
Neuropsychiatric Symptoms in Different Subtypes of Mild Cognitive Impairment
台灣老年醫學暨老年學雜誌, Nov 1, 2015
Background: Mild cognitive impairment (MCI) is considered to be an intermediate cognitive state b... more Background: Mild cognitive impairment (MCI) is considered to be an intermediate cognitive state between the normal cognitive aging and dementia. Different MCI subtypes are classified by the number and characteristics of the affected cognitive domains. Neuropsychiatric symptoms (NPS) in dementia and MCI have been extensively studied, but little is known about its prevalence in MCI subtypes. In this study, we aimed to investigate NPS in different MCI subtypes. Methods: In this cross-sectional study, a total of 159 MCI subjects were recruited from the outpatient clinics of two hospitals in Taiwan from 2007-2011. All participants received baseline diagnostic evaluations, including medical history, physical examinations, neurologic and neuropsychological assessments. MCI patients were classified into different subtypes, including amnestic (aMCI), non-amnestic (non-aMCI), single-domain MCI, and multiple-domain MCI. The Neuropsychiatric Inventory was used to assess NPS. The prevalence and score of each neuropsychiatric symptom were compared between aMCI and non-aMCI, and between single-domain and multiple-domain MCI subtypes. Results: Of the 159 subjects with MCI, 99 (62.3%) met the criteria for aMCI, 60 (37.7%) for non-aMCI, 75 (47.2%) for single-domain MCI, and 84 (52.8%) for multiple-domain MCI. The non-aMCI group was associated with more prevalent anxiety and a higher anxiety score than the aMCI group. The difference became insignificant after controlling for age, sex, education and MMSE. When compared with the single-domain MCI group, the multiple-domain MCI group was more likely to have at least one NPS (63.1% vs. 45.3%, p=0.027), more prevalent apathy (26.2% vs. 13.3%, p=0.049), and a higher apathy score. After controlling for covariates, multiple-domainMCI group was still more likely to have at least one NPS (p=0.042). Conclusions: Our findings suggest that multiple-domain MCI is associated with more prevalent NPS than single-domain MCI. More studies are needed to determine the prevalence and pathophysiology of the NPS in different MCI subtypes.
Journal of Personalized Medicine, 2022
Cognitive dysfunction is associated with functional impairment of patients with Major Depressive ... more Cognitive dysfunction is associated with functional impairment of patients with Major Depressive Disorder (MDD). The goals were to explore the associated factors of cognitive impairment in MDD and to develop and validate a brief and culture-relevant questionnaire, the Taiwan Cognition Questionnaire (TCQ), among patients with MDD. This was a cross-sectional, multi-center observational study of MDD patients in Taiwan. Participants of Group 1 from 10 centers contributed to the validation of the TCQ by their response and sociodemographics. The participants of Group 2 from one center received an objective cognitive assessment for clarification of the relationship between the TCQ score and its associated factors. In Group 1, 493 participants were recruited. As for Group 2, an extra 100 participants were recruited. The global Cronbach’s alpha for the TCQ was 0.908. According to the coordinates of the ROC curve, 9/10 was the ideal cut-off point. With the criteria, the sensitivity/specificit...
Identifying dopamine supersensitivity through a randomized controlled study of switching to aripiprazole from other antipsychotic agents in patients with schizophrenia
Therapeutic Advances in Psychopharmacology, 2022
Background: Aripiprazole has been reported to worsen psychotic symptoms when switching from other... more Background: Aripiprazole has been reported to worsen psychotic symptoms when switching from other antipsychotics, possibly due to dopamine supersensitivity psychosis. Objective: This study aimed to explore the predictors and possible underlying mechanisms of aripiprazole-related psychotic exacerbation. Methods: We conducted an 8-week, open-label, randomized controlled study from October 2007 to September 2009, assigning patients with a primary diagnosis of schizophrenia or schizoaffective disorder to switch from other antipsychotics to aripiprazole with 2-week dual administration, and then to taper off the original agents in fast (n = 38, within 1 week) or slow (n = 41, within 4 weeks) strategies. Positive and Negative Syndrome Scale (PANSS) was examined at day 0, 7, 14, 28, 56. Aripiprazole-related exacerbation (ARE) was defined positive as a 2-point increase in delusion/hallucination dimension score within 28 days compared with baseline. Baseline demographic, clinical and interven...
BMC Psychiatry, 2020
Background Switching to aripiprazole from other antipsychotics can avoid antipsychotic-induced hy... more Background Switching to aripiprazole from other antipsychotics can avoid antipsychotic-induced hyperprolactinemia but may result in an abnormally low prolactin level. This study aimed to assess whether the aripiprazole-induced abnormally low prolactin level was a biomarker for subsequent rebound of positive symptoms in schizophrenia patients. Methods Participants were 63 patients in an 8-week trial of switching to aripiprazole, in which preswitching antipsychotics were maintained for the first 2 weeks and aripiprazole was fixed at 15 mg orally throughout the trial. A prolactin level of < 3.7 ng/ml was defined as abnormally low, and an increase of two or more points in the positive subscore of the Positive and Negative Syndrome Scale at two adjacent ratings was defined as a psychotic rebound. Results Among 63 patients, 25 (39.7%) had an abnormally low prolactin level and 21 (33.3%) had a psychotic rebound after switching to aripiprazole. In patients with abnormally low prolactin l...
Alzheimer's & Dementia, 2020
Background: Agitation is highly prevalent in patients with dementia and off-label use of antipsyc... more Background: Agitation is highly prevalent in patients with dementia and off-label use of antipsychotic agents for agitation is common. But antipsychotic agents are clearly associated with increased adverse effects. A recent study found dextromethorphan (DXM) and low dose quinidine may be effective for the management of agitation in patients with Alzheimer disease (AD). Methods: This is an open-label, 10-week study. Eligible dementia patients (AD or VaD) were enrolled. These patients received DXM 60 mg/day from Day 1 through Day 7. If the symptoms of agitation were not reduced, the dose might be gradually increased to 240 mg/day. The primary endpoint was score change in agitation domain of the Neuropsychiatric Inventory (NPI), and secondary endpoints include change on NPI total score and subscores, CGI, and MMSE. Results: A total of 16 patients were recruited. The mean (SD) of age was 79.3 (9.9) years, with male to female ratio 1:1. The mean (SD) of MMSE was 9.7 (9.7). At baseline, CGI-Severity for agitation was 4 to 6 (mean=4.9), The mean and SD of behavioral disturbances were: 8.4 (3.5) for NPI agitation score, 8.1 (4.3) for NPI irritability score, 7.6 (4.8) for NPI aberrant motor behavior, and 58.8 (33.7) for NPI total score. At the endpoint, the mean dose of DXM was 150 mg/day. There was a significant decrease of the score of behavioral disturbance: 3.8 (3.0) for NPI agitation score (p<0.001), 4.2 (3.9) for NPI irritability score (p<0.001), 2.3 (3.9) for NPI aberrant motor behavior (p<0.036), and 24.4 (19.6) for NPI total score (p<0.001). The CGI-I on agitation revealed 69% (n=11) with much/very much improved, 25% (n=4) minimal improved, and 6% (n=1) minimally worse. There were some mild to moderate adverse effects reported, including malaise, anemia, drowsiness, skin itching, and increased appetite. No severe adverse effects were found. Conclusions: The results of this preliminary study suggest DXM 60-240 mg/day seem quite efficacious for the treatment of agitation in dementia and without severe adverse reactions. It may be suitable for short-term use for control of agitation in elderly dementia patients.
Protocol of guided antipsychotic reduction to reach minimum effective dose ( GARMED ) in patients with remitted psychosis based on pragmatic design
Early Intervention in Psychiatry, 2021
Patients with psychosis intend to discontinue antipsychotic treatment for various reasons. As ant... more Patients with psychosis intend to discontinue antipsychotic treatment for various reasons. As antipsychotic discontinuation involves a high risk of relapse, maintenance treatment is recommended by mainstream opinion even when remission is attained. To optimize the risk‐to‐benefit ratio of long‐term antipsychotic treatment, we proposed an operationalized guided dose‐reduction algorithm to serve as an intermediate approach as to achieve the lowest effective antipsychotic dose and better functioning for patients with remitted psychosis.
Journal of the Formosan Medical Association = Taiwan yi zhi, 2003
BACKGROUND AND PURPOSE There has been a marked increase in the prevalence of alcoholism in the Ta... more BACKGROUND AND PURPOSE There has been a marked increase in the prevalence of alcoholism in the Taiwanese population over the past 6 decades. This study was designed to establish a Taiwanese Brief Alcoholism Screening Questionnaire (BASQ) for use in early detection in medical and public health settings. METHODS Interview data were collected from the database of the Taiwan Psychiatric Epidemiological Project (TPEP). The TPEP interviews had been conducted using the Chinese-modified version of the Diagnostic Interview Schedule (DIS-CM) that included a section on alcoholism diagnosis. Data collected from a community sample of 13,373 subjects was used in this study. Twenty nine DIS-CM items for alcoholism diagnosis were entered into an analytic model with 7 statistical filters to identify cross-cultural items. A brief alcoholism screening questionnaire was constructed using these selected items. The validity of the questionnaire was tested in subjects (n = 457) recruited from a local medi...
Outcome and Cognitive Impairment of Dsm-Iv Schizophreni: A 5-Year Follow- Up
Schizophrenia Bulletin, 2005
Characteristics of Parasuicide Patients Using Acetaminophen Overdose
A quarter of century after: The changing ecology of psychiatric emergency services
Asia-Pacific Psychiatry, 2021
INTRODUCTION Previous studies demonstrated a trend of increasing common mental disorders among th... more INTRODUCTION Previous studies demonstrated a trend of increasing common mental disorders among the Emergency Department (ED) visitors in Western countries. Little is known about the current conditions of the emergency psychiatric services in Asian countries. This study aims to survey the current epidemiology and the changing ecology of emergency psychiatry services in Taiwan. METHODS A total of 804 psychiatry consultations were initiated at the ED during the 1-year period from July 1, 2014 to June 30, 2015 in a medical center in northern Taiwan. Clinical data of gender, age, chief complaints, tentative diagnoses, dispositions, and ED staying hours were compared to a previous report in the same hospital in 1988. RESULTS Psychiatry consultation was initiated in 0.72% of all ED visits (804/111,923). Among these visits, females were 1.73 times of the males. The most common chief complaints were psychosis/mania (33.5%) and suicide/self-harm (33.2%), followed by homicide/violence (12.8%) and anxiety/depression (10.3%). Top tentative diagnoses were schizophrenia spectrum and other psychotic disorders (31.3%), trauma- and stressor-related disorders (17.5%), bipolar disorders (15.9%), and depressive disorders (14.2%). Compared to 1988, there are three major changes: (1) over-representation of female patients, (2) an increase of "neurosis" patients, and (3) an increase of suicide/self-harm as chief problem. DISCUSSION This study portrays the current epidemiology and changing ecology of psychiatric emergency in Taiwan. The increase of neurotic and suicide/self-harm patients requires more services and clinical training in managing common mental disorders and suicide in the ED.
Antipsychotic Prescriptions for Patients with Dementia: The Strengths and Weaknesses of the National Health Insurance System of Taiwan
Taiwanese Journal of Psychiatry, 2020
Risk of Intracranial Hemorrhage With Concomitant Use of Antidepressants and Nonsteroidal Anti-inflammatory Drugs: A Nested Case-Control Study
Annals of Pharmacotherapy, 2020
Background Whereas previous studies found that concomitant antidepressant and nonsteroidal anti-i... more Background Whereas previous studies found that concomitant antidepressant and nonsteroidal anti-inflammatory drug (NSAIDs) use may increase the risk of gastrointestinal bleeding, either drug alone increases the risk of intracranial hemorrhage (ICH). Objective To assess the risk for ICH in patients on concomitant treatment with antidepressants and NSAIDs. Methods This was a nested case-control study using national insurance claims data in Taiwan between 2005 and 2013. Drug exposure was measured and compared during 3 time windows: 1 to 30, 31 to 60, and 61 to 90 days before the index date, which is the date of the ICH event. Both traditional and newer-generation antidepressants were considered in this study. Results Patients exposed to both antidepressants and NSAIDs 1 to 30 days before the index date presented a 50% increased odds of developing ICH (OR: 1.53; 95% CI: 1.31-1.80) compared with patients receiving antidepressants alone. Specifically, the concomitant use of nonselective N...
P3‐611: Potential Risk Predictors of Complex Sleep Behaviors for Patients with Dementia or Mild Cognitive Impairment
Alzheimer's & Dementia, 2018
Frontiers in Psychiatry, 2019
Background: Auditory event-related potentials (ERPs) have been utilized to study defective inform... more Background: Auditory event-related potentials (ERPs) have been utilized to study defective information processing of patients with schizophrenia. To delineate the pathophysiological processes from pre-psychotic state to first-episode psychosis, a study on subjects from ultra-high-risk (UHR) state to first-episode psychosis, ideally in an antipsychotic-free condition, can add important information to our understanding. Methods: Patients with UHR state or at their first-episode psychosis (FEP) who were drug-naive or only have been temporarily treated with antipsychotics were assessed by auditory ERPs measurement, including P50/N100 (sensory gating) and duration mismatch negativity (MMN; deviance detection). A group of age-matched healthy subjects served as their controls. Results: A total of 42 patients (23 UHR and 19 FEP) and 120 control subjects were recruited, including 21 pure drug-naive and 21 with very short exposure to antipsychotics. Collapsing FEP and UHR as a patient group, they exhibited significant sensory deficits manifested as larger P50 S2 amplitude, larger N100 ratio, and smaller N100 difference, and significantly less deviance detection response revealed by MMN. Such differences were less significant when treating FEP and UHR separately for comparisons. Comparisons of ERP results between drug-naive subjects and antipsychotic-short-exposure subjects revealed no significant difference in any P50/N100 and MMN parameter. Conclusion: Our study is one of the few studies focused on drug-naive or minimally treated patients at pre-or early-psychotic states. Our results exhibited impaired performance in sensory gating and deviance detection shown by certain parameters. A longitudinal study with larger sample sizes will be helpful to provide more evidence to elucidate the role of antipsychotics on an individual's neurophysiological performance at different stages of psychosis.
Journal of Human Genetics, 2019
Disrupted-in-schizophrenia 1 (DISC1) was reported to be associated with schizophrenia. In a previ... more Disrupted-in-schizophrenia 1 (DISC1) was reported to be associated with schizophrenia. In a previous study, we found significant association with schizophrenia patients with deficient sustained attention assessed by continuous performance test (CPT). This study aimed to identify risk polymorphisms in this specific neurocognitive subgroup and investigate the expression of different isoforms of DISC1. A total of 83 genetic variants were identified through direct sequencing in 50 controls and 100 schizophrenia patients. Fourteen variants were genotyped in 600 controls and 912 patients. Patients were subgrouped by familial loading (multiplex or simplex) and performance on CPT. The frequency of AA genotype of rs11122324 at the 3′-UTR of Es and Esv1 isoforms and of rs2793091 at intron 4 were significantly higher in multiplex schizophrenia patients than those in controls (corrected p < 0.05). In further subgrouping, the frequency of AA genotype of the two SNPs were significantly higher in multiplex schizophrenia patients with deficient sustained attention than those in controls (corrected p < 0.005). The mRNA expression levels of two extra-short isoforms (Es and Esv1) in the EBVtransformed lymphocytes of schizophrenia were significantly higher than those of controls. Luciferase reporter assays demonstrated that the A-allele of rs11122324 significantly upregulated DISC1 extra-short isoforms transcription compared with the G-allele. We found two SNPs (rs11122324 and rs2793091) of DISC1 may be specifically associated with multiplex schizophrenia patients with deficient sustained attention. The SNP rs11122324 may be a risk polymorphism, which may have functional influence on the transcription of Es and Esv1 through increasing their expression.
Biological Psychiatry, 2019
BACKGROUND: Whether the paternal age effect on schizophrenia is a causation or just an associatio... more BACKGROUND: Whether the paternal age effect on schizophrenia is a causation or just an association due to confounding by selection into late parenthood is still under debate. We investigated the association between paternal age and offspring's early-onset of schizophrenia controlling for both paternal and maternal predisposition to schizophrenia as empirically estimated using polygenic risk score (PRS) derived from Psychiatric Genomics Consortium. METHODS: Among 2923 sporadic schizophrenia cases selected from the Schizophrenia Trio Genomic Research in Taiwan project, 1649 had parents' genotyping data. The relations of paternal schizophrenia PRS to paternal age at first birth (AFB) and that of maternal schizophrenia PRS to maternal AFB were examined. A logistic regression model of patients' early-onset (≤ 18) on paternal age was conducted. RESULTS: Advanced paternal age over 20 exhibited a trend of an increasing proportion of early-onset (odds ratio per 10-year increase in paternal age = 1.28, p = 0.007) after adjusting for maternal age, sex, and age. Older paternal AFB also exhibited an increasing trend of paternal schizophrenia PRS. Additionally, a U-shaped relationship between maternal AFB and maternal schizophrenia PRS was observed. After adjusting for both paternal and maternal schizophrenia PRS, the association of paternal age with patients' early-onset remained (odds ratio = 1.29, p = 0.04). CONCLUSIONS: The association between paternal age and the early-onset schizophrenia is not confounded by parental PRS to schizophrenia, which captures partially parental genetic vulnerability to schizophrenia. Our findings support an independent role of paternal age per se in the increased risk of early-onset offspring.
Correlates of Dependence and Beliefs About the Use of Hypnotics Among Zolpidem and Zopiclone Users
Substance Use & Misuse, 2014
Zolpidem and zopiclone are the two most commonly prescribed Z-drugs approved to treat insomnia. T... more Zolpidem and zopiclone are the two most commonly prescribed Z-drugs approved to treat insomnia. To examine the demographic and clinical correlates of dependence and beliefs about hypnotic use among long-term zolpidem and zopiclone users in psychiatric treatment for insomnia. A total of 392 psychiatric outpatients who received zolpidem or zopiclone treatment for at least 3 months for insomnia were studied. Participants&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; severity of hypnotic dependence and beliefs about the use of hypnotics to treat sleep problems were assessed. The correlation of dependence and beliefs about zolpidem and zopiclone treatment with demographic characteristics, hypnotic-using behaviors, co-use of addictive substances, and depressive symptoms were analyzed using multiple regression analysis models. Zolpidem users reported more severe dependence and a lower level of necessity regarding the use of hypnotics than zopiclone users did. High equivalent doses of hypnotics and long duration of use were significantly associated with severe dependence and a low level of necessity. Severe depressive symptoms were signiciantly associated with severe dependence, a low level of necessity, and a low level of concern. Educational level was also associated with the levels of concern and necessity. Conclusions/Importance: There were differences in the level of dependence and belief about hypnotic use between zolpidem and zopiclone users. The correlates of dependence and belief identified in this study can serve as the basis for prevention and intervention programs.
Schizophrenia Research, 2010
genes is not very successful as the enormous investments that are made on the genotypic level (e.... more genes is not very successful as the enormous investments that are made on the genotypic level (e.g., genotyping ∼1,000,000 SNPs) are not matched by similar investments on the phenotypic level. We aim to improve the assessment of individual differences in schizophrenia. Methods: We performed Latent Class Factor Analysis on 76 Comprehensive Assessment of Psychiatric History (CASH) symptoms in a sample of 2,290 patients with schizophrenia, schizophreniform, schizoaffective disorder, bipolar disorder or depression, and 1,888 healthy controls from the Netherlands. IQ was assessed in a subsample (N=2.373). Results: Exploratory factor analyses show that variation in schizophrenia symptoms is best represented by five latent dimensions (positive, negative, mania, disorganisation, and depression). For each individual, factor scores were estimated on each of these five dimensions. Latent class analysis was applied to the individual factor scores and showed the existence of eight clusters of subjects. Patients diagnosed with a psychotic disorder were assigned to three of these classes which were separated based on the scores on the disorganisation and negative dimensions while scores on the remaining dimensions were high irrespective of class. Controls and subjects with depression were most often assigned to healthy or moderately affected classes, but were also assigned to the three "affected" classes. Linear regression analyses, with diagnosis included as a covariate, showed that IQ was significantly associated with the dimensions negative, depression, and disorganisation. A relatively high IQ was associated with low scores on the negative and disorganisation dimensions and a high score on depression. Univariate analyses of variance showed differences between latent classes. Within the schizophrenia and schizoaffective patients, IQ scores were below average in the two classes which obtained high scores on the negative dimension, and were about average in the class which obtained a low score on the negative dimension. Within controls (including subjects diagnosed with depression), subjects who were assigned to one of the three "affected" classes, obtained lower IQ scores than subjects who were assigned to a relatively healthy class. Discussion: Despite the fact that schizophrenia is a highly heterogeneous disorder, gene finding studies collapse patients with different symptom patterns into one group. However, if in reality these patients have distinct genetic vulnerabilities, this would dramatically decrease the statistical power to detect functional genetic variants. We show large phenotypic heterogeneity both within patients with a psychotic disorder and within controls. This phenotypic heterogeneity is associated with IQ. Future Genome Wide Association studies should take this heterogeneity into account.
Molecular Psychiatry, 2007
Calcineurin is a calcium/calmodulin-dependent protein phosphatase composed of two subunits, a reg... more Calcineurin is a calcium/calmodulin-dependent protein phosphatase composed of two subunits, a regulatory subunit of calcineurin B (CNB) and a catalytic subunit of calcineurin A (CNA). PPP3CC is the c isoform of CNA located at the chromosome 8p21.3 region. To evaluate the association between PPP3CC and schizophrenia in the Taiwanese population, 10 single nucleotide polymorphism (SNP) markers across the gene were genotyped by the method of MALDI-TOF in 218 schizophrenia families with at least two affected siblings. One SNP (rs2272080) located around the exon 1 untranslated region was nominally associated with schizophrenia (P = 0.024) and significantly associated with the expression of PPP3CC in lymphoblast cell line; the TT and TG genotype had significantly higher relative expression levels than the GG genotype (P = 0.0012 and 0.015, respectively). In further endophenotype stratification, the single locus of rs2272080 and the haplotypes of both two-SNP haplotype (rs7833266-rs2272080) and seven-SNP haplotype (rs2461491-rs2469758-rs2461489-rs2469770-rs2449340-rs1482337-rs2252471) showed significant associations with the subgroup of schizophrenia with deficits of the sustained attention as tested by the continuous performance test (CPT, P < 0.05) and the executive functioning as tested by the Wisconsin Card Sorting Test (WCST, P < 0.05). The results suggest that PPP3CC gene may be a true susceptibility gene for schizophrenia.
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Papers by Tzung-Jeng Hwang