Variant GADL1 and response to lithium therapy in bipolar I disorder.

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

Examining the Application of the DC-IA-A Diagnostic Criteria for Internet Addiction Disorder in At-Risk College Students.

Internet addiction disorder is a relatively new condition, and the criteria for its diagnosis have been developed only over the last several years. The criteria for Internet addiction remain controversial. We strive to further elucidate the clinical validity of the diagnostic criteria for Internet addiction. To test items of the diagnostic criteria for Internet addiction among adolescents, we conducted a clinical interview study of college students based on longitudinal data on their risky use of the Internet. Forty-one high-risk cases were selected from a 3-year 5-time point longitudinal survey of 716 college freshmen. We examined disputes relevant to symptoms and impairment in the DC-IA-A (Diagnostic Criteria for Internet Addiction among Taiwanese Adolescents). Of the 41 cases, 21 were diagnosed with Internet addiction via a psychiatric interview. In the Internet addiction disorder group, 23.8% of cases had a diagnosis of depression, whereas only 15.0% of the cases in the non-Internet addiction group had a diagnosis of depression. Two major criteria (A8 and A3) had low incidences in these high-risk college students and thus did not help provide a differential diagnosis between the groups. We suggest that A8, 'excessive effort spent on activities necessary to obtain access to the Internet', should be omitted, and that A3, 'tolerance: a marked increase in the duration of Internet use needed to achieve satisfaction', should be modified. A1 and A9 should be discussed regarding their role in the diagnosis of Internet addiction disorder. Additional well-designed studies examining the diagnostic criteria and the relationship between factors are needed.

Examining the diagnostic criteria for Internet addiction: Expert validation.

BACKGROUND/PURPOSE: Internet addiction is the coming problem around the world. The diagnostic criteria for Internet addiction among adolescents (DC-IA-A) has become a widely used measure for assessing the presence of Internet addiction in Taiwan. This study examined the diagnosis criteria for Internet addiction in adolescents by expert evaluation. METHODS: Twenty psychiatrists rated the adequacy of each criterion in DC-IA-A. The content validity and homogeneity reliability proposed by Aiken were calculated. RESULTS: The coefficients content validity and homogeneity reliability showed twenty psychiatrists agreed on each of DC-IA-A as relevant to the diagnosis of Internet addiction, though several criteria need improvements. Two criteria "excessive time spent on Internet activities and leaving the Internet" and "excessive effort spent on activities necessary to obtain access to the Internet" should be omitted, and the criteria of "tolerance" should be modified. CONCLUSION: The diagnostic criteria for Internet addiction among adolescents should be revised to meet the real condition of this population.

Sleep complaints and memory in psychotropic drug-free euthymic patients with bipolar disorder.

BACKGROUND/PURPOSE: Few studies have been conducted examining the genuine sleep condition and memory in patients with euthymic bipolar disorder. Thus we evaluated sleep complaints and memory functions in psychotropic drug-free euthymic patients with bipolar disorder. METHODS: Twenty-two psychotropic drug-free euthymic patients with bipolar disorder and 44 healthy controls matched by age and sex were recruited and assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Wechsler Memory Scale-Revised (WMS-R). RESULTS: The quality of sleep and memory function of the euthymic patients with bipolar disorder were significantly poorer than those of the controls. Both years of education and the hypnotic use sub-item of the PSQI were significantly correlated with visual memory index of the WMS-R. CONCLUSION: Sleep complaints management is important in euthymic patients with bipolar disorder.

High dosage of aripiprazole-induced dysphagia.

BACKGROUND: Dysphagia as a main manifestation of extrapyramidal symptoms is an uncommon adverse effect of second-generation antipsychotics. METHOD: We present a 54-year-old drug-naïve patient with schizophrenia, who developed dysphagia with aripiprazole 30 mg daily treatment. RESULTS: This is the first case report on aripiprazole-induced dysphagia. We discuss the risk factors that led to dysphagia in this case. CONCLUSION: Aripiprazole-induced dysphagia is rare, and it is important to be aware that it does occur with high-dosage treatment.

Clinical features of delirious mania: a series of five cases and a brief literature review.

BACKGROUND: Little is known about the cause and psychopathology of delirious mania, a type of disorder where delirium and mania occur at the same time. This condition still has no formal diagnostic classification. To provide more information about this potentially life-threatening condition, we studied five patients with delirious mania. METHODS: We describe the cases of five patients with delirious mania admitted to an acute inpatient psychiatric unit between January 2005 and January 2007, and discuss the cases in the context of a selective review of the clinical literature describing the clinical features and treatment of delirious mania. RESULTS: Two patients had two episodes of delirious mania. Delirium usually resolved faster than mania though not always the case. Delirious mania remitted within seven sessions of the electroconvulsive therapy (ECT). CONCLUSIONS: Delirious mania is a potentially life-threatening but under-recognized neuropsychiatric syndrome. Delirious mania that is ineffectively treated may induce a new-onset manic episode or worsen an ongoing manic episode, and the patient will need prolonged hospitalization. Delirious mania also has a close relationship with catatonia. Early recognition and aggressive treatment, especially with electroconvulsive therapy, can significantly reduce morbidity and mortality.

Suicide Ideation among Outpatients with Alcohol Use Disorder.

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.

A Multi-Center Study for the Development of the Taiwan Cognition Questionnaire (TCQ) in Major Depressive Disorder.

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/specificity of the TCQ was 0.610/0.689. The TCQ score was positively associated with a history of being admitted to acute psychiatric care and the severity of depression and negatively associated with objective cognitive measures. The TCQ provides a reliable, valid, and convenient measure of subjective cognitive dysfunction in patients with MDD.

Escitalopram for psychogenic nausea and vomiting: a report of two cases.

Psychogenic nausea and vomiting is defined as vomiting without any obvious organic pathology or vomiting with a psychological etiology. The treatment for such a condition is a challenge in clinical practice. The first patient was a 46-year-old married factory worker who was repeatedly hospitalized for recurring bouts of nausea and vomiting. After consultation, she was diagnosed with major depressive disorder. The frequency of nausea and vomiting decreased after treatment with daily doses of 10-20 mg escitalopram. The second patient was a 37-year-old married teacher who had bouts of nausea and vomiting and was also hospitalized repeatedly. She was diagnosed with mixed anxiety-depressive disorder. After treatment with 10 mg/day escitalopram, her episodes of nausea and vomiting decreased. Escitalopram may be an effective treatment for psychogenic nausea and vomiting associated with depression.

Application of electroconvulsive therapy in treatment of retinitis pigmentosa comorbid with major depressive disorder and panic disorder.

A substantial proportion of retinitis pigmentosa (RP) patients have depression/anxiety and a phobic pathology that may be related to changes in melatonin secretion. We discuss electroconvulsive therapy (ECT) in a patient with RP comorbid with depression and panic disorder. A 51-year-old man was admitted because of major depression, panic disorder, and RP. Ultrabrief pulse (0.3 millisecond) right unilateral ECT was performed 9 times in total. The symptoms relieved, and patient tolerated the treatments well. Electroconvulsive therapy increases serum melatonin, providing therapeutic effects in depression. The application of ECT in this population therefore appears to be an alternative treatment.

Taiwan Expert Consensus Recommendations for Switching to Aripiprazole Long-Acting Once-Monthly in Patients with Schizophrenia.

In the last decade, long-acting injectable antipsychotics has been widely used in schizophrenia. Aripiprazole long-acting once-monthly (AOM) is the only long-acting dopamine partial agonist antipsychotic approved for schizophrenia; however, a literature search revealed no guidance on safely switching from oral and long-acting injectable antipsychotics to AOM. This study aimed to develop recommendations of AOM use based on existing data and expert consensus. A committee of 30 experts in psychopharmacology from major hospitals across Taiwan was invited. A modified Delphi method was conducted, consisting of two rounds of questionnaires, literature review, three rounds of face-to-face discussion meeting, and two rounds of anonymous voting. The consensus recommendations were developed based on existing data, clinical experiences, and consensus opinions, with 80% agreement among panel members required for final adoption. The panel developed nine consensus statements of switching to AOM for both acute and stable schizophrenia patients receiving oral or long-acting injectable atypical antipsychotics. Recommendations regarding dose adjustment of oral medication and pregnancy/breastfeeding were also included. The nine consensus recommendations provide a guidance on safely switching to AOM. Substantial gaps in knowledge, and more research is necessary.

Comparison of intramuscular olanzapine, orally disintegrating olanzapine tablets, oral risperidone solution, and intramuscular haloperidol in the management of acute agitation in an acute care psychiatric ward in Taiwan.

INTRODUCTION: The purpose of this study was to compare efficacy and safety among intramuscular olanzapine, intramuscular haloperidol, orally disintegrating olanzapine tablets, and oral risperidone solution for agitated patients with psychosis during the first 24 hours of treatment in an acute care psychiatric ward. METHODS: Forty-two inpatients from an acute care psychiatric ward of a medical center in central Taiwan were enrolled. They were randomly assigned to 1 of the 4 treatment groups (10-mg intramuscular olanzapine, 10-mg olanzapine oral disintegrating tablet, 3-mg oral risperidone solution, or 7.5-mg intramuscular haloperidol). Agitation was measured by using the excited component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation-Calmness Evaluation Scale, and the Clinical Global Impression--Severity Scale during the first 24 hours. RESULTS: There were significant differences in the PANSS-EC total scores for the 4 intervention groups at 15, 30, 45, 60, 75, and 90 minutes after the initiation of treatment. More significant differences were found early in the treatment. In the post hoc analysis, the patients who received intramuscular olanzapine or orally disintegrating olanzapine tablets showed significantly greater improvement in PANSS-EC scores than did patients who received intramuscular haloperidol at points 15, 30, 45, 60, 75, and 90 minutes after injection. CONCLUSIONS: These findings suggest that intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution are as effective treatments as intramuscular haloperidol for patients with acute agitation. Intramuscular olanzapine and disintegrating olanzapine tablets are more effective than intramuscular haloperidol in the early phase of the intervention. There is no significant difference in effectiveness among intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution.

A single-blind, comparative study of zotepine versus haloperidol in combination with a mood stabilizer for patients with moderate-to-severe mania.

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

A 64-week, multicenter, open-label study of aripiprazole effectiveness in the management of patients with schizophrenia or schizoaffective disorder in a general psychiatric outpatient setting.

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

Prolonged psychosis associated with interferon therapy in a patient with hepatitis C: case study and literature review.

BACKGROUND: Although rare, psychosis can emerge during interferon (IFN)-alpha therapy and persist after therapy is completed. OBJECTIVE: The authors report the case of a 30-year-old man with hepatitis C infection treated with IFN-alpha and ribavirin who developed acute psychosis with persecutory delusions and auditory hallucinations, resulting in a suicide attempt. METHOD: The patient was treated with amisulpride for 6 weeks and then with risperidone for 6 weeks. RESULTS: There was no improvement in symptoms until the patient was treated with quetiapine; he then had a marked recovery from the psychotic symptoms. The duration of the psychosis was 28 weeks. CONCLUSION: Hepatitis C can be successfully treated with IFN therapy, and the risk of IFN-induced psychosis is low, with psychotic symptoms resolving in most cases after completion of IFN therapy with or without antipsychotic treatment. In prolonged psychosis induced by IFN, quetiapine might also be of benefit.

The association between cigarette smoking and obstructive sleep apnea.

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 non-smokers. RESULTS: Smokers had significantly higher apnea-hypopnea index (p<0.001) for non-rapid eye movement sleep stage, higher apnea-hypopnea index (p<0.001) for total sleep time, and higher snore frequency (p<0.001) in t-test analysis. They also demonstrated higher Epworth Sleepiness Scale scores, shorter sleep times, lower percentage of slow-wave (deep) sleep, and longer snore times. However, no significant association was found between cigarette smoking and OSA after adjusting for sex, age, and BMI (OR=1.02, 95% CI: 0.66-1.57). CONCLUSIONS: We did not find any significant association between cigarette smoking and OSA after adjusting for age, sex, and BMI. Further well-designed prospective controlled cohort studies might clarify the relationship between cigarette smoking and OSA.

Depression is differently associated with sleep measurement in obstructive sleep apnea, restless leg syndrome and periodic limb movement disorder.

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.

Association between Thioridazine Use and Cancer Risk in Adult Patients with Schizophrenia-A Population-Based Study.

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.