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Objective Although both partners of a married couple can have mental disorders, the concordant and cross-concordant categories of disorders in couples remain unclear. Using national psychiatric population-based data only from patients with mental disorders, we examined married couples with mental disorders to examine spousal concordance and cross-disorder concordance across the full spectrum of mental disorders.Methods Data from the 1997 to 2012 Taiwan Psychiatric Inpatient Medical Claims data set were used and a total of 662 married couples were obtained. Concordance of mental disorders was determined if both spouses were diagnosed with mental disorder of an identical category in the International Classification of Diseases, Ninth Revision, Clinical Modification; otherwise, cross-concordance was reported.Results According to Cohen’s kappa coefficient, the most concordant mental disorder in couples was substance use disorder, followed by bipolar disorder. Depressive and anxiety disorders were the most common cross-concordant mental disorders, followed by bipolar disorder. The prevalence of the spousal concordance of mental disorders differed by monthly income and the couple’s age disparity.Conclusion Evidence of spousal concordance and cross-concordance for mental disorders may highlight the necessity of understanding the social context of marriage in the etiology of mental illness. Identifying the risk factors from a common environment attributable to mental disorders may enhance public health strategies to prevent and improve chronic mental illness of married couples.

This study aimed to examine the institutionalization rate in patients with dementia in Taiwan, identify the predictors of institutionalization, and conduct a mediation analysis of caregiver burden between neuropsychiatric symptoms and institutionalization. We analyzed data from a retrospective cohort registered in dementia collaborative care ( N = 518). The analyses applied univariate and multivariate Cox proportional hazard regression with Firth’s penalized likelihood to assess the relationship between each predictor at entry and institutionalization for survival analysis. Thirty (5.8%) patients were censored due to institutionalization after a median follow-up of one-and-a-half years. Neuropsychiatric symptoms, loss of walking ability, and living alone predicted institutionalization. Caregiver burden may partially mediate the effects of neuropsychiatric symptoms and institutionalization. High caregiver burden due to presence of neuropsychiatric symptoms may partially contribute to institutionalization among people living with dementia in Taiwan. However, proper management of neuropsychiatric symptoms and caregiver empowerment may ameliorate institutionalization risk.

Background Bipolar disorder (BD) is associated with cognitive impairment and mitochondrial dysfunction. However, the associations among mitochondrial DNA copy number (MCN), treatment response, and cognitive function remain elusive in BD patients. Methods Sixty euthymic BD patients receiving valproate (VPA) and 66 healthy controls from the community were recruited. The indices of metabolic syndrome (MetS) were measured. Quantitative polymerase chain reaction analysis of blood leukocytes was used to measure the MCN. Cognitive function was measured by calculating perseverative errors and completed categories on the Wisconsin Card Sorting Test (WCST). The VPA treatment response was measured using the Alda scale. Results BD patients had significantly higher MCN, triglyceride, and C-reactive protein (CRP) levels, waist circumference, and worse performance on the WCST than the controls. Regression models showed that BD itself and the VPA concentration exerted significant effects on increased MCN levels. Moreover, the receiver operating characteristic curve analysis showed that an MCN of 2.05 distinguished VPA responders from nonresponders, with an area under the curve of 0.705 and a sensitivity and specificity of 0.529 and 0.816, respectively. An MCN level ≥2.05 was associated with 5.39 higher odds of being a VPA responder (P = .006). BD patients who were stratified into the high-MCN group had a higher VPA response rate, better WCST performance, lower CRP level, and less MetS. Conclusions The study suggests a link between the peripheral MCN and cognitive function in BD patients. As an inflammatory status, MetS might modulate this association.

Although agomelatine may be associated with an increased risk of hepatotoxicity, the incidence rate of acute hepatitis seemed divergent between clinical trials and daily practice. Whether aging or gender is a risk factor in developing hepatotoxicity due to agomelatine is not clear. We present 3 older female cases with acute hepatitis occurring due to highly probable idiosyncratic drug-induced liver injury caused by agomelatine. From these cases, regular surveillance on liver function in the older women taking antidepressants would be of benefits.

Cheng-Chen Chang, 1, 2,* Wen-Fu Wang, 3, 4,* Yi-Ying Li, 5,* Yu-An Chen, 1 Yen-Jen Chen, 1 Yi-Cheng Liao, 1 Kai-Ming Jhang, 3 Hsin-Hung Wu 5– 7 1Department of Psychiatry, Changhua Christian Hospital, Changhua, Taiwan; 2School of Medicine, Chung Shan Medical University, Taichung City, Taiwan; 3Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan; 4Department of Holistic Wellness, Ming Dao University, Changhua, Taiwan; 5Department of Business Administration, National Changhua University of Education, Changhua, Taiwan; 6Department of M-Commerce and Multimedia Applications, Asia University, Taichung City, Taiwan; 7Faculty of Education, State University of Malang, Malang, East Java, Indonesia*These authors contributed equally to this workCorrespondence: Hsin-Hung Wu Email hhwu@cc.ncue.edu.twPurpose: The purpose of this study was to identify the caring scenarios that result in severe depression in caregivers caring for dementia patients.Patients and Methods: A cross-sectional study with 1111 dementia patients and their caregivers in Taiwan from October 2015 to January 2020 was conducted. Gender, age, type of dementia, clinical dementia rating, walking ability, mood symptoms, behavioral symptoms, and psychological symptoms were the variables from the dementia patients. Age, relation to the patient, employment, type of primary care, frequency of care, mood symptoms, and the score from the Center for Epidemiologic Studies Depression Scale were the variables from the caregivers. A comprehensive viewpoint of both dementia patients and their caregivers was evaluated by the Apriori algorithm to find the attributes resulting in different caregiving depressions.Results: Forty-seven rules were found with 18 rules of mild depressive symptomatology, 17 rules of moderate depressive symptomatology, and 12 rules of severe depressive symptomatology. A total of 7 general rules were summarized to be the severe depressive symptomatology. The results showed that an unemployed or retired caregiver with the mood symptoms such as helplessness, anger, emotional liability, or anxiety who took care of AD patients or AD patients with a moderate severity would have severe depression. Increased care frequencies (≥ 6 days per week) and multiple mood problems from caregivers result in severe depression. The composition of adult children, patients’ aggression, and caregivers’ helplessness as well as the combinations of male patients aged 75– 84 years with the caregiver’s mood of helplessness or nervousness and hopelessness were highly associated with severe depression.Conclusion: For those caring for AD patients, severe depression was associated with the combination of different parameters to constitute each of these seven scenarios. Unlike previous studies which often evaluated one or two variables related to caregiver’s depression, this study provided a more comprehensive viewpoint that enabled the collaborative team to efficiently identify and manage different scenarios by summarizing the rules of caregivers with severe depression from a systematic viewpoint.Keywords: patient with dementia, Alzheimer’s disease, behavioral and psychological symptoms of dementia, caregiver, caregiver’s mood, depressive symptomatology, Center for Epidemiologic Studies Depression Scale, caring scenario, Apriori algorithm

Yu-An Chen,1,* Cheng-Chen Chang,1,2,* Wen-Fu Wang,3,4,* Ya-Sian Lin,5 Kai-Ming Jhang,3 Tzu-Ying Lo,5 Hsin-Hung Wu5– 7 1Department of Psychiatry, Changhua Christian Hospital, Changhua, Taiwan; 2School of Medicine, Chung Shan Medical University, Taichung City, Taiwan; 3Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan; 4Department of Holistic Wellness, Ming Dao University, Changhua, Taiwan; 5Department of Business Administration, National Changhua University of Education, Changhua, Taiwan; 6Department of M-Commerce and Multimedia Applications, Asia University, Taichung City, Taiwan; 7Faculty of Education, State University of Malang, Malang, East Java, Indonesia*These authors contributed equally to this workCorrespondence: Hsin-Hung WuNational Changhua University of Education, No. 2 Shida Road, Changhua City, 500, TaiwanTel +886 4 7232105 ext. 7412Fax +886 4-7211292Email hhwu@cc.ncue.edu.twPurpose: This study examined the attributes causing higher burdens for caregivers caring for female patients with Alzheimer’s disease by analyzing a combination of various variables, including demographic data, dementia severity, and neuropsychiatric symptoms.Patients and Methods: This study included 99 female patients with Alzheimer’s disease who were cared for by the dementia collaborative care team at Changhua Christian Hospital, Taiwan. Neuropsychiatric symptoms used in this study included affections (9 types), behavior symptoms (9 symptoms), and psychological symptoms (3 symptoms). The Apriori algorithm was employed to identify association rules that reveal the relationships among demographic data, dementia severity, neuropsychiatric symptoms, and caregivers’ burden.Results: A total of 185 rules were determined, including 51 rules with little or no burden, 108 rules with mild to moderate burden, and 26 rules with moderate to severe burden. The major findings are as follows. Neuropsychiatric symptoms were associated with varying degrees of caregivers’ burden among female patients aged 75 to 84 years with mild dementia. Crying spells and aggression were specifically associated with a moderate to severe burden. Delusion was associated with a mild to moderate and moderate to severe burden. Dysthymia and depression were associated with little or no burden to moderate to severe burden.Conclusion: Clinicians can provide early interventions to reduce the burden of caregivers caring for female patients with Alzheimer’s disease and can refer caregivers for timely assistance to reduce their burden.Keywords: Alzheimer’s disease, female patients, female patients with Alzheimer’s disease, neuropsychiatric symptom, Apriori algorithm, caregiving burden

Introduction. Individuals with substance use disorders, particularly those with alcohol use disorder (AUD), have a high risk of suicide. Therefore, identifying risk factors for suicide in these individuals is crucial. Methods. This retrospective study reviewed the medical records of individuals with AUD who participated in an alcohol treatment program in central Taiwan during 2019–2020. We collected data using the Cut down, Annoyed, Guilty, and Eye-opener questionnaire, Alcohol Use Disorders Identification Test (AUDIT), Brief Michigan Alcoholism Screening Test (MAST), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and a suicidal ideation question. Furthermore, we collected information on several related variables, namely, sex, age, marital status, years in school, employment status, family history of alcohol problems, age at first exposure to alcohol, duration of alcohol use, history of alcohol cessation, history of domestic violence, and history of drunk driving. In total, 136 individuals were recruited to participate in this study. Results. The suicidal ideation group had significantly younger participants, a higher proportion of women, a higher proportion of participants with a history of domestic violence, a greater severity of alcohol addiction (based on both AUDIT and MAST scores), higher depression scores, higher anxiety scores, less social support, a lower quality of life (World Health Organization Quality of Life (WHOQOL)), and poorer sleep quality (Pittsburgh Sleep Quality Index, PSQI) compared with the nonsuicidal ideation group. The suicidal ideation score was correlated with the AUDIT score after age, and BDI, BAI, WHOQOL, and PSQI scores were controlled for ( P = 0.034 ). Conclusion. Individuals with higher AUDIT scores visiting a clinic for alcohol treatment might have a higher risk of suicidal ideation. Therefore, clinicians should pay close attention to the suicidal ideation problem in this population. Furthermore, appropriate medication or management programs for suicide prevention should be considered.

Background: Using data from the National Health Insurance (NHI) of Taiwan, we conducted a nationwide population-based cohort study to investigate the association between antidepressant (ATD) use and the risk of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) who had received interferon (IFN) therapy. Methods: This study included a total of 274,952 HCV-infected patients without hepatitis B virus infection who were enrolled in the NHI program between January 1, 1997 and December 31, 2013. Among these patients, only 10,713 (age ≥18 years) had received IFN therapy between 2004 and 2008. Among the patients who had received IFN therapy, 2014 had received ATDs, and 8684 had not. A Cox proportional hazards regression model was applied after adjusting for age, sex, income, urbanization, medical comorbidity, and medication use. Results: Compared with non-ATD-treated patients, ATD-treated patients were more likely to receive a diagnosis of alcohol-related disease, diabetes mellitus (DM), hypertension, and hyperlipidemia. ATD-treated patients had a significantly lower incidence of HCC than non-ATD-treated patients (P = 0.0019). Female, older (age ≥50 years), and non-DM patients who had received cumulative high doses of ATDs had a significantly lower risk of HCC than non-ATD-treated patients. After adjustment, only high-dose selective serotonin reuptake inhibitor (SSRI) use was inversely associated with HCC risk (adjusted hazard ratio 0.37, 95% confidence interval 0.19–0.71, P = 0.0027). Conclusions: Our study showed that ATD use, especially a relatively high cumulative dose of SSRIs, in HCV-infected patients who had received IFN was associated with reduced HCC risk. Future clinical studies are warranted to explore the underlying mechanisms and to apply them to newer direct-acting antiviral agent treatments.

Objective Several cell line studies have demonstrated thioridazine's anticancer, multidrug resistance-reversing and apoptosis-inducing properties in various tumors. We conducted this nationwide population-based study to investigate the association between thioridazine use and cancer risk among adult patients with schizophrenia. Methods Based on the Psychiatric Inpatient Medical Claim of the National Health Insurance Research Database of Taiwan, a total of 185,689 insured psychiatric patients during 2000 to 2005 were identified. After excluding patients with prior history of schizophrenia, only 42,273 newly diagnosed patients were included. Among them, 1,631 patients ever receiving thioridazine for more than 30 days within 6 months were selected and paired with 6,256 randomly selected non-thioridazine controls. These patients were traced till 2012/12/31 to see if they have any malignancy. Results The incidence rates of hypertension and cerebrovascular disease were higher among cases than among matched controls. The incidence of hyperlipidemia, coronary artery disease and chronic pulmonary disease did not differ between the two groups. By using Cox proportional hazard model for cancer incidence, the crude hazard ratio was significantly higher in age, hypertension, hyperlipidemia, cerebrovascular disease, coronary artery disease and chronic pulmornary disease. However, after adjusting for other covariates, only age and hypertension remained significant. Thioridazine use in adult patients with schizophrenia had no significant association with cancer. Conclusion Despite our finding that thioridazine use had no prevention in cancer in adult patients with schizophrenia. Based on the biological activity, thioridazine is a potential anticancer drug and further investigation in human with cancer is warranted.

BackgroundThe decreased life expectancy and care costs of mental disorders could be enormous. However, research that compares mortality and utilization concurrently across the major category of mental disorders is absent. This study investigated all-cause mortality and medical utilization among patients with and without mental disorders, with an emphasis on identifying the psychiatric category of high mortality and low medical utilization.MethodsA total of 570,250 individuals identified from the 2002–2013 Taiwan National Health Insurance Reearch Database consistuted 285,125 psychiatric patients and 285,125 non-psychiatric peers through 1:1 dual propensity score matching (PSM). The expenditure survival ratio (ESR) was proposed to indicate potential utilization shortage. The category of mental disorders and 13 covariates were analyzed using the Cox proportional hazard model and general linear model (GLM) through SAS 9.4.ResultsPSM analyses indicated that mortality and total medical expenditures per capita were both significantly higher in psychiatric patients than those in non-psychiatric patients (allPP P P ConclusionSubstance use disorders are the category of highest YPLL but notably in insufficient utilization. Health care utilization in patients with substance use disorders should be augmented timely after the diagnosis, especially toward home and community care. The factors related to mortality and utilization identified by this study merit clinical attention.

Introduction Obstructive sleep apnea (OSA) is a serious sleep disorder characterized by repetitive episodes of paused or shallow breathing during sleep. Patients with OSA often have excessive daytime sleepiness. The role of cigarette smoking in OSA remains controversial. The aim of this study was to examine the relationship between cigarette smoking and OSA. Methods In this retrospective chart review, we reviewed 18-month sleep laboratory charts in central Taiwan. We collected data regarding sleep, current cigarette smoking status, sex, age, body mass index (BMI), neck circumference, Epworth Sleepiness Scale score, and polysomnographic sleep parameters. In total, 733 subjects were recruited; among these, 151 were smokers and 582 were nonsmokers. Results Smokers had significantly higher apnea–hypopnea index (p

Differences in child abuse perpetration between individuals with and without mental disorders remain obscure. This study compared the risk difference and further investigated the association between the category of mental disorders and child abuse perpetration. A total of 681,970 adults from the 2002 to 2013 Taiwan National Health Insurance Research Database were analyzed, including 340,985 patients with psychiatric disorders (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 290.x–319.x) and 340,985 sex- and age-matched individuals without psychiatric disorders. Child abuse perpetration (ICD-9-CM N-codes 995.5x and E-code E967) was the outcome variable. Matched analyses indicated that the risk of child abuse among patients with psychiatric disorders (0.25%) was significantly higher than that among those without psychiatric disorders (0.16%; odds ratio [OR] = 1.464, p < .0001). Among the six categories of mental disorders, the prevalence rates of committing child abuse were significantly higher for personality disorders, substance use, and affective disorders (0.56%, 0.45%, and 0.40%, respectively; p < .0001). Compared with anxiety disorders, substance use disorders were significantly associated with higher odds of child abuse perpetration (OR = 2.032, p < .05), especially physical abuse (OR = 2.018, p < .0001). Psychiatric morbidity was associated with higher odds of child abuse, with substance use determined as the major risk category. Screening high-risk families by using the associated factors is crucial.

Depression causes sleep disturbance and is associated with various sleep-related disorders. However, how depression affects the symptomatic presentation of different sleep-related disorders is unclear. In this study, we investigated the sleep parameters of different sleep-related disorders between depressive and non-depressive patients. A total of 785 patients underwent polysomnography in a mental hospital from Jan 2012 to Jun 2013. We first analyzed variables between the depressive and non-depressive groups. The patients were then divided into four groups: obstructive sleep apnea (OSA, n = 339), restless leg syndrome (RLS, n = 51), periodic limb movement disorder (PLMD, n = 58) and comorbid group (OSA and RLS, n = 46). We next compared sleep measures between the depressive and non-depressive subjects within each groups. The patients with OSA and depression were significantly associated with a higher periodic limb movement index. Significantly more patients with RLS patients and depression had initial insomnia complaints. However, significantly more patients with PLMD and depression middle insomnia. Compared with non-depressive population, depressive patients had higher comorbidity with RLS and PLMD. Depression may have different association with the sleep parameters in different sleep-related disorders. Further investigations are needed to investigate how these findings may affect patients' awareness and clinicians' diagnosis and management of sleep-related disorders.

In this prospective study, we investigated the effects of antidepressant therapy on total antioxidant capacity and free radical levels in patients with major depressive disorder (MDD). We recruited thirty-five first-episode patients who met the criteria of the Fourth Edition of Diagnostic and Statistical Manual of Mental Disorders of MDD and 35 age- and sex-matched healthy controls. Superoxide and hydroxyl radicals were measured to investigate oxidative status and the total radical-trapping antioxidant parameter (TRAP) assay was performed to evaluate antioxidant capacity in healthy controls and in patients before and after receiving a 12-week regimen of sertraline. The severity of depression was evaluated using the 17-item Hamilton Depression Rating Scale (HDRS). Before treatment, the mean HDRS score in patients with MDD was 26.11±4.93. Of the 35 patients with MDD, 19 (54.29%) completed the 12-week treatment regimen and all achieved remission. Patients with MDD had significantly lower TRAP baseline values than healthy controls. After adjusting for age, sex, occupation, education and marital status, we found that HDRS score was negatively correlated with TRAP value and level of superoxide radicals. After treatment, the MDD group demonstrated significantly higher TRAP values and significantly lower levels of superoxide and hydroxyl radicals. In conclusion, MDD patients are accompanied by lowered antioxidant capacity than healthy individuals. Antidepressant treatment for 12 weeks results in increased antioxidant capacity and a decrease in circulating free radicals. Key words: major depressive disorder; antidepressant; antioxidant capacity; free radical, total radical-trapping antioxidant parameter (TRAP)

Delirium is common in daily practice. Drug-induced delirium constitutes approximately one-third of all cases of delirium. In cases characterized by the limited efficacy of a single antidepressant, a combination of two antidepressants is required, which may induce a complex drug-drug interaction. We reviewed a case of duloxetine- and bupropion-related delirium in an elderly male patient in our clinical practice. The patient was diagnosed with major depressive disorder and was treated with duloxetine. However, he developed delirium 10 days after bupropion was added to his treatment regimen. Three days after the cessation of bupropion, his delirious condition gradually improved. Duloxetine and bupropion are both cytochrome P450 2D6 inhibitors that may result in a higher level of hydroxybupropion. An increased level of hydroxybupropion may cause the elevation of dopamine and a risk of subsequent delirium. We should be aware of the risk of delirium induced by drug-drug interactions.

Aim The aim of this study was to compare alterations of mitochondrial DNA (mtDNA) copy number, single nucleotide polymorphisms, and oxidative damage of mtDNA in clinically stable patients with bipolar I disorder (BD). Methods Patients meeting DSM-IV diagnostic criteria for BD were recruited from the psychiatric outpatient clinic at Changhua Christian Hospital, Taiwan. They were clinically stable and their medications had not changed for at least the preceding 2 months. Exclusion criteria were substance-induced psychotic disorder, eating disorder, anxiety disorder or illicit substance abuse. Comparison subjects did not have any history of major psychiatric disorders and they were non-smokers. By analyzing peripheral blood leukocytes, copy number, single nucleotide polymorphisms and oxidative damage of mtDNA were compared between the two groups. Results The median age of the subjects was 38 years and 41.5 years in the comparison and BD groups, respectively. The leukocyte mtDNA copy number of the BD group was significantly lower than that of the comparison group (P

Major depressive disorder (MDD), the most prevalent mental disorder is a global public health issue. The aim of this study was to assess the association between low income and major depressive disorder (MDD) by age and sex. The National Health Insurance Research Database (NHIRD) of Taiwan was used to retrieve data. A total of 1,743,948 participants were eligible for the study. Low-income individuals were identified from 2001 and 2003 (specifically, Group Insurance Applicants, ie, category"51" or "52") and followed from 2004 to 2010. MDD was identified using the ICD-9-CM 296.2 and 296.3 codes. Among non-low-income individuals, the MDD incidence rates increased with age in both males and females, that is, 0.35, 0.93, 0.97, 1.40 per 10,000 person-months for males and 0.41, 1.60, 1.89, 1.95 per 10,000 person-months for females aged 0 to 17, 18 to 44, 45 to 64, and ≥65 years, respectively. Low-income females (18-44 years) and males (45-64 years) had the highest incidence of MDD, which was 3.90 and 3.04, respectively, per 10,000 person-months. Among low and non-low-income individuals, the MDD incidence rates were higher in the females than males in all age groups. Males aged 45 to 64 and 0 to 17 years had highest hazard ratios (HR) of 2.789 (95% confidence interval [CI], 1.937-4.014) and 2.446 (95% CI, 1.603-3.732), respectively. The highest HRs for females were 2.663 (95% CI, 1.878-3.775) and 2.219 (CI, 1.821-2.705) in the 0 to 17 and 18- to 44-year age groups. Low income was not found to serve as a risk factor for the development of MDD in males and females aged ≥65 years. Among the non-low-income males and females, the incidence rates of MDD were found to increase with age. Low income was found to serve as a significant risk factor for MDD only in individuals under age 65.

Non-clinical schizotypy was found to be related to poorer Wisconsin Card-Sorting Test (WCST) performance, but the results were inconsistent. Two subgroups, the higher negative–higher positive and the lower negative–lower positive (15 vs 16), were selected from the top and the bottom quartiles of negative and positive scale scores of the Schizotypal Personality Questionnaire (SPQ) completed by 177 healthy volunteers, respectively. The higher negative–higher positive SPQ score subgroup had significantly poorer performance regarding the completed categories of WCST than the lower negative–lower positive SPQ score subgroup. Subjects with higher non-clinical schizotypy trait showed relatively mild cognitive dysfunction.

Postmortem studies have documented abnormalities in the dorsolateral prefrontal cortex (dlPFC) in depressed subjects. In this study we used magnetic resonance imaging to test for dlPFC volume differences between older depressed and non-depressed individuals. Eighty-eight subjects meeting DSM IV criteria for major depressive disorder and thirty-five control subjects completed clinical evaluations and cranial 3T magnetic resonance imaging. After tissue types were identified using an automated segmentation process, the dlPFC was measured in both hemispheres using manual delineation based on anatomical landmarks. Depressed subjects had significantly lower gray matter in the left and right dorsolateral prefrontal cortex (standardized to cerebral parenchyma) after controlling for age and sex. Our study confirmed the reduction of dorsolateral prefrontal cortex in elderly depressed subjects, especially in the gray matter. These regional abnormalities may be associated with psychopathological changes in late-life depression.

The role of olanzapine in treatment-resistant schizophrenia has still not been clearly resolved. In addressing this issue, the current report presents an open-label, prospective, 13 week trial with olanzapine use in Chinese schizophrenic patients who were resistant to more than two different classes of antipsychotics during a minimal 4 week treatment period for each antipsychotic drug at adequate dosage. Fifty-one inpatients were recruited after a cross-titration period and given 10-25 mg of olanzapine daily, without any concomitant antipsychotic medication. Patients were evaluated with the Brief Psychotic Rating Scale (BPRS), the Positive and Negative Symptoms Scale, the Clinical Global Impression Scale (CGI), the Abnormal Involuntary Movement Scale, the Simpson-Angus scale, and the Barnes Akathisia Scale. The olanzapine-treated patients showed significant improvement in both the positive and negative symptoms of schizophrenia by the end of the study. Overall, 20 of 51 (39.2%) responded to 10-25 mg of olanzapine per day as measured by the BPRS and CGI scores. Five patients dropped out due to the worsening of their psychotic symptoms, two patients discontinued owing to poor drug compliance, and the remaining patient complained of a lack of efficacy. Extrapyramidal side-effects were mild, and anticholinergic medications required has decreased. The present open study suggests that olanzapine may be effective and well-tolerated in Chinese treatment-resistant schizophrenic patients. Further double-blinded trials are needed to confirm this result.

Catatonia is a clinical syndrome consisting of catalepsy and waxy flexibility, mutism, rigidity, negativism, and stereotypy. It was first described by Kahlbaum and then considered as a purely psychiatric condition. Although commonly associated with schizophrenia upon influences of Kraepelin and Bleuler, there were several reports associating catatonia and mood disorders as well as general medical conditions. Benzodiazepine withdrawal and alcohol withdrawal induced catatonia have been previously reported in the literature. Here, we present a case of catatonia that occurred after zolpidem withdrawal.

The aim of this study was to compare alterations of mitochondrial DNA (mtDNA) copy number, single nucleotide polymorphisms, and oxidative damage of mtDNA in clinically stable patients with bipolar I disorder (BD).Patients meeting DSM-IV diagnostic criteria for BD were recruited from the psychiatric outpatient clinic at Changhua Christian Hospital, Taiwan. They were clinically stable and their medications had not changed for at least the preceding 2 months. Exclusion criteria were substance-induced psychotic disorder, eating disorder, anxiety disorder or illicit substance abuse. Comparison subjects did not have any history of major psychiatric disorders and they were non-smokers. By analyzing peripheral blood leukocytes, copy number, single nucleotide polymorphisms and oxidative damage of mtDNA were compared between the two groups.The median age of the subjects was 38 years and 41.5 years in the comparison and BD groups, respectively. The leukocyte mtDNA copy number of the BD group was significantly lower than that of the comparison group (P 0.001). BD patients had significantly higher mitochondrial oxidative damage than the comparison group (6.1 vs 3.9, P 0.001). After generalized linear model adjusting with age, sex, smoking, family history, and psychotropic use, mtDNA copy number was still significantly lower in the BD group (P 0.001). MtDNA oxidative damage was positively correlated with age (P = 0.034), although mtDNA oxidative damage was similar between these two groups.Possible involvement of oxidative stress and mitochondria in the pathophysiology of BD needs more large-scale studies. It is important that psychiatrists retain a high level of suspicion for mitochondrial dysfunction in patients with bipolar disorder.

OBJECTIVE This study aims to investigate association between early recognizable minor physical abnormality (MPA) during childhood is associated with mental health problems in young adults. METHODS In 1984, 169 preschool children in central Taiwan underwent a detailed physical examination for subtle abnormalities (MPA). Fourteen years later, the Brief Symptom Rating Scale (BSRS) and Chinese Health Questionnaire (CHQ) were used to measure specific psychiatric symptoms. RESULTS There is an association between MPA during childhood and adult characterized with interpersonal sensitivity, anxiety, depression and paranoid mental health symptoms. CONCLUSION The signs of childhood MPA can be easily identified and should be regarded as risk factors when predicting mental disorder. Mental health professionals should consider MPAs as important signs for possible development of emotional problems.

Non-clinical schizotypy was found to be related to poorer Wisconsin Card-Sorting Test (WCST) performance, but the results were inconsistent. Two subgroups, the higher negative-higher positive and the lower negative-lower positive (15 vs 16), were selected from the top and the bottom quartiles of negative and positive scale scores of the Schizotypal Personality Questionnaire (SPQ) completed by 177 healthy volunteers, respectively. The higher negative-higher positive SPQ score subgroup had significantly poorer performance regarding the completed categories of WCST than the lower negative-lower positive SPQ score subgroup. Subjects with higher non-clinical schizotypy trait showed relatively mild cognitive dysfunction.

To the Editor: Spinocerebellar ataxia (SCA) is an inherited disorder of brain function characterized by progressive incoordination of gait and is often associated with poor coordination of hands, speech, and eye movements. It is a slowly progressive disease that gradually worsens over a period of years. Zolpidem is a nonbenzodiazepine sedative in the imidazopyridine class and is chemically distinct from other sedatives. It is a short-acting hypnotic with a selective agonist effect for γ-aminobutyric acid (GABA) type A receptors in the brain. It was considered originally by physicians as almost devoid of abuse and dependence potential. Intriguingly, aside from its hypnotic effect, zolpidem has been shown to improve catatonia,1 aphasia,2 Parkinson's disease,3 and ataxia.4 However, reports of zolpidem abuse or dependence are increasing,5,6 and more attention should be paid in terms of zolpidem withdrawal. We report a patient with SCA who took zolpidem for movement difficulties initially, developed dependence on high-dose zolpidem treatment, and encountered serious withdrawal symptoms. We also review the literature on the possible mechanism for the effect of zolpidem on SCA. Case report. Ms A, a 40-year-old married woman, was referred in 2009 for psychiatric consultation due to high-dose zolpidem use. She was diagnosed with SCA type IV at age 35 years with initial symptoms of unsteady gait and mild slurred speech. Her father and brother were also afflicted with SCA. This time, she was admitted via emergency department to our neurology department because of loss of consciousness. Generalized seizure lasted for 1 minute at home, and initial management at the emergency department with phenytoin intravenous drip terminated further progression. Toxicology testing detected no plasma alcohol, whereas plasma benzodiazepine level was 64.80 ng/mL. She claimed she had abused triazolam and alcohol during early adulthood due to insomnia. Other illicit substance use was denied. She had started taking zolpidem 3 years earlier for insomnia, and, paradoxically, zolpidem relieved her ataxia and spasticity. She recalled being able to move her arms and turn her trunk more easily, although the improvement lasted only around 1 hour after taking zolpidem. The dose of zolpidem was gradually escalated by the patient to reach optimal effect. The dose usually amounted to 1,000 mg/d for the past year. Nausea, palpitation, jitters, hand tremor, and perspiration were noted if she did not take enough zolpidem. She was bedridden due to SCA and was cared for by her husband. Although she consumed high doses of zolpidem, her husband tried to cater to all her needs out of sympathy. Zolpidem had been prescribed from different physicians. Withdrawal seizures were noted several times if her supply of zolpidem fell short. Ms A was detoxified by taper of zolpidem gradually over 2 weeks. We prescribed trazodone 100 mg before sleep and diazepam 20 mg/d and propranolol 30 mg/d for anxiety. No seizure attack was noted during hospitalization. After this 2-week hospitalization, she was referred to the psychiatric clinic for further management. The imidazopyridine hypnotic zolpidem binds preferably to the α1 subtype of the benzodiazepine receptor, which is part of GABAA receptor complex. This highly accounts for its sedative effect, whereas the anxiolytic action of benzodiazepines appears to be mediated by receptors that contain the α2 subunit.7 Zolpidem at high doses might lose its selectivity on α1 subunits and bind to lower-affinity α2 units, leading to an anxiolytic effect. Thus, high-dose zolpidem may have a paradoxical effect for alleviating anxiety, and abrupt discontinuation would produce withdrawal symptoms such as palpitation, anxiety, tremor, or seizure similar to those seen with benzodiazepine withdrawal. There is no definite treatment that can prevent or slow the progression of SCA. Clauss et al4 reported transient improvement of SCA with zolpidem in 4 cases. Single photon emission computed tomography demonstrated that GABAergic function may be decreased in the cerebral cortex, thalamus, striatum, and cerebellum in patients with SCA.8 Zolpidem has been shown to mildly improve catatonia, aphasia, and Parkinson's disease.9 Such motor improvement may be due to selective inhibition by zolpidem of GABAergic inhibitory neurons in the internal globus pallidus and substantia nigra pars reticulata, resulting in activation of the thalamus and cerebral cortex.9 Positron emission tomography imaging also has shown normalized tracer uptake in the left thalamus and cerebellum after treatment with zolpidem.4 Our case further corroborates that zolpidem has a mode of action apart from hypnotic properties. To our knowledge, this is the first case report concerning high-dose zolpidem withdrawal seizure in a patient with SCA. We should be more cautious in prescribing zolpidem to patients with past drug abuse or dependence to prevent unwanted consequence. Further investigation of the pharmacologic efficacy of zolpidem in SCA might be needed.

A sensitive high-performance CZE combining on-column field-amplified sample injection (FASI) has been developed for simultaneous determination of aripiprazole and its active metabolite, dehydroaripiprazole, in human plasma. A sample pretreatment by means of liquid-liquid extraction (LLE) (diethyl ether) with subsequent quantitation by FASI-CZE was used. The separation of aripiprazole and dehydroaripiprazole was performed using a BGE containing 150 mM phosphate buffer (pH 3.5) with 40% methanol and 0.02% PVA as a dynamic coating to reduce interaction of analytes with the capillary wall. Before sample loading, a methanol plug (0.3 psi, 6 s) was injected to permit FASI for stacking. The samples were injected electrokinetically (10 kV, 30 s) to introduce sample cations and the applied voltage was 20 kV with on-column detection at 214 nm. Several parameters affecting the separation and sensitivity of the drug and its active metabolite were studied, including reconstitution solvent, organic modifier, pH and concentration of phosphate buffer. The linear ranges of the method for test drug and its active metabolite, in plasma using amlodipine as an internal standard, were over the range 5.0-100.0 ng/mL. One female volunteer (25 years old) was orally administered a single dose of 10 mg aripiprazole (Abilify, Otsuka) and blood samples were drawn over a 60 h period for pharmacokinetic study. The method was also applied to monitor the concentration of aripiprazole and dehydroaripiprazole in plasma collected after oral administration of 20 or 30 mg aripiprazole (Abilify, Otsuka) daily at steady state in one schizophrenic patient.

Background To compare alterations of mitochondria DNA (mtDNA) copy number, single nucleotide polymorphisms (SNPs), and oxidative damage of mtDNA in clinically stable patients with major depressive disorder (MDD). Methods Patients met DSM-IV diagnostic criteria for MDD were recruited from the psychiatric outpatient clinic at Changhua Christian Hospital, Taiwan. They were clinically stable and their medications had not changed for at least the preceding two months. Exclusion criteria were substance-induced psychotic disorder, eating disorder, anxiety disorder or illicit substance abuse. Comparison subjects did not have any major psychiatric disorder and they were medically healthy. Peripheral blood leukocytes were analyzed to compare copy number, SNPs and oxidative damage of mtDNA between the two groups. Results 40 MDD patients and 70 comparison subjects were collected. The median age of the subjects was 42 years and 38 years in MDD and comparison groups, respectively. Leukocyte mtDNA copy number of MDD patients was significantly lower than that of the comparison group (p = 0.037). MDD patients had significantly higher mitochondrial oxidative damage than the comparison group (6.44 vs. 3.90, p