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The search for susceptibility genes underlying the heterogeneous bipolar disorder has been inconclusive, often with irreproducible results. There is a hope that narrowing the phenotypes will increase the power of genetic analysis. Early-onset bipolar disorder is thought to be a genetically homogeneous subtype with greater symptom severity. We conducted a genome-wide association study (GWAS) for this subtype in bipolar I (BPI) disorder. Study participants included 1779 patients of Han Chinese descent with BPI disorder recruited by the Taiwan Bipolar Consortium. We conducted phenotype assessment using the Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry and prepared a life chart with graphic depiction of lifetime clinical course for each of the BPI patient recruited. The assessment of onset age was based on this life chart with early onset defined as ≤20 years of age. We performed GWAS in a discovery group of 516 early-onset and 790 non-early-onset BPI patients, followed by a replication study in an independent group of 153 early-onset and 320 non-early-onset BPI patients and a meta-analysis with these two groups. The SNP rs11127876, located in the intron of CADM2, showed association with early-onset BPI in the discovery cohort (P = 7.04 × 10-8) and in the test of replication (P = 0.0354). After meta-analysis, this SNP was demonstrated to be a new genetic locus in CADM2 gene associated with early-onset BPI disorder (P = 5.19 × 10-8).

Objectives: Schizophrenia is associated with an increased risk of suicide. Few studies have investigated the risk of suicide across different ages, likely due to limitations around sample size. Methods: From the National Health Insurance Research Database in Taiwan, this study identified 195,787 patients with schizophrenia from January 1, 2000, to December 31, 2019. During the study period, 3848 patients died from suicide. We calculated the standardized mortality ratio (SMR) for suicide stratified by age. In this age‐stratified, nested case–control study, risk set sampling was used to match each case with 4 living controls by age, sex, and the year of the first diagnosis with schizophrenia. Conditional logistic regression was used for estimating age‐stratified risk profiles. Results: The SMR was the highest in the <25 years age group (52.8) and inversely correlated with age. Unemployment was associated with an increased risk of suicide in the 25 to 34, 35 to 44, 45 to 54, and 55 to 64 years age groups. Depressive and sleep disorders before suicide were more common among suicide cases with schizophrenia than among controls across all age groups. Drug‐induced and alcohol‐induced mental disorders were significantly associated with suicide but were observed only in the age group younger than 54. Heart disease, pneumonia, and moderate or severe renal disease were risk factors for suicide in the age groups less than 65. Conclusions: The risk factors for suicide differ by age. This study's findings can be used to optimize health‐care interventions for preventing suicide in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Sepsis constitutes a condition that involves life-threatening organ dysfunction induced by severe infection. This nested case–control study investigated risk factors for severe sepsis and whether antipsychotic use is associated with severe sepsis risk in patients with schizophrenia, a topic that has not been comprehensively explored in previous studies. Methods: We selected 39,432 patients with schizophrenia aged between 15 and 65 years from Taiwan's Psychiatric Inpatient Medical Claims database for the period 2000–2012. The case group comprised patients with severe sepsis after their first psychiatric admission (n = 1382). The case and control groups were randomly matched (1:4) by age, sex and first psychiatric admission (year) and finally comprised 1382 and 5528 individuals, respectively. We employed multivariable conditional logistic regression to identify (1) risk factors (physical illnesses and nonpsychiatric medications) and (2) antipsychotic–severe sepsis associations. Results: Higher numbers of psychiatric admissions and physical illnesses such as delirium, cerebrovascular disease and cancer were significantly associated with a higher risk of severe sepsis. Furthermore, severe sepsis was associated with the use of antithrombotic agents, systemic corticosteroids and agents targeting the renin–angiotensin system. Clozapine (adjusted risk ratio = 1.65) and quetiapine (adjusted risk ratio = 1.59) use were associated with an increased risk of severe sepsis. The use of more than one antipsychotic drug could further increase this risk. Conclusion: Several physical illnesses and nonpsychiatric medications increase the risk of severe sepsis in patients with schizophrenia. Specifically, clozapine or quetiapine use significantly increased the risk of severe sepsis in these patients. [ABSTRACT FROM AUTHOR]

Background: Individuals with schizophrenia face high mortality risks. The effects of lipid-modifying agents on this risk remain understudied. Aim: This study was conducted to investigate the effects of lipid-modifying agents on mortality risk in people with schizophrenia. Method: This nationwide cohort study collected the data of people with schizophrenia from Taiwan's National Health Insurance Research Database for the period between 1 January 2001 and 31 December 2019. Multivariable Cox proportional hazards regression with a time-dependent model was used to estimate the hazard ratio for mortality associated with each lipid-modifying agent. Results: This study included 110 300 people with schizophrenia. Of them, 22 528 died (19 754 from natural causes and 1606 from suicide) during the study period, as confirmed using data from Taiwan's national mortality database. The use of lipid-modifying agents was associated with reduced risks of all-cause (adjusted hazard ratio [aHR]:0.37; P < 0.001) and natural (aHR:0.37; P < 0.001) mortality during a 5-year period. Among the lipid-modifying agents, statins and fibrates were associated with reduced risks of all-cause mortality (aHRs:0.37 and 0.39, respectively; P < 0.001 for both) and natural mortality (aHRs: 0.37 and 0.42, respectively; P < 0.001 for both). Notably, although our univariate analysis indicated an association between the use of lipid-modifying agents and a reduced risk of suicide mortality, the multivariate analysis revealed no significant association. Conclusions: Lipid-modifying agents, particularly statins and fibrates, reduce the risk of mortality in people with schizophrenia. Appropriate use of lipid-modifying agents may bridge the mortality gap between these individuals and the general population. [ABSTRACT FROM AUTHOR]

Background: Patients with asthma experience more physical, psychological, and financial burdens; a link between asthma and suicidality has been reported in research. Purpose: This study analyzed the medical utilization and comorbidity before their self-injurious behavior in patients with asthma. Methods: We enrolled 186,862 patients newly diagnosed with asthma between 1999 and 2013 from the National Health Insurance Research Database in Taiwan. A total of 500 case subjects had ever conducted self-injurious behaviors during the study period. Based on a nested case-control study, each case was matched with 10 controls derived from the asthma cohort to analyze differences between them and their medical use models. Results: The results indicated that, compared to the control group, the cases presented higher frequencies of outpatient visits and hospitalizations. Regarding comorbidity, the cases had more cardiovascular diseases (adjusted odds ratio [aOR]=1.58; p< 0.001), bipolar disorder (aOR=2.97; p< 0.001), depression (aOR=4.44; p< 0.001), and sleep disorder (aOR=1.83; p< 0.001) than the controls. Conclusion: The evidence-based information serves as a reference for medical staff to reduce the occurrence of self-injurious behavior in patients with asthma. [ABSTRACT FROM AUTHOR]

Case management (CM)-based community therapy for patients with schizophrenia had little effect on reducing suicide mortality. We investigate the long-term suicide mortality outcome and associated risk factors in patients with schizophrenia receiving homecare (CM) in Taiwan. We enrolled a nationwide cohort of patients with schizophrenia who newly received homecare CM intervention (n = 13 317) between January 1, 2001, and December 31, 2015; their data were derived from Taiwan's National Health Insurance Research Database. We calculated the incidence rate of suicide methods. We examined the demographic and medical utilization profile for suicide and then performed a nested case–control study and multivariate regression to identify independent risk factors for suicide mortality. Among the 13 317 patients who received homecare CM intervention, 1766 died during the study period, of whom 213 died by suicide, which is the leading cause of unnatural death. Jumping from a high place, self-poisoning, and hanging were the top 3 suicide methods. Increased medical utilization was noted for both psychiatric and non-psychiatric services within 3 months of suicide mortality. Comorbidities of depressive disorder, nonspecific heart diseases, pneumonia, and gastrointestinal ulcers were identified as independent risk factors for suicide mortality. Suicide was the leading cause of unnatural mortality in patients with schizophrenia receiving homecare CM intervention in Taiwan. We noted the preferred suicide methods, high medical utilization, and comorbidities before suicide. Thus, we suggest that the CM team should assess lethal methods for suicide and ensure that patients adhere to psychiatry treatment for improving the current care model for this specified population. [ABSTRACT FROM AUTHOR]

Background: Examining patients with first-episode psychosis (FEP) provides opportunities to better understand the mechanism underlying these illnesses. By incorporating quantitative measures in FEP patients, we aimed to (1) determine the baseline distribution of clinical features; (2) examine the impairment magnitude of the quantitative measures by comparing with external controls and then the counterparts of schizophrenia patients of different familial loadings; and (3) evaluate whether these quantitative measures were associated with the baseline clinical features. Methods: Patients with FEP were recruited from one medical center, two regional psychiatric centers, and two private clinics in northern Taiwan with clinical features rated using the Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale. Quantitative measurements included the Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), niacin response abnormality (NRA), and minor physical anomalies and craniofacial features (MPAs). To evaluate the relative performance of the quantitative measures in our FEP patients, four external comparison groups from previous studies were used, including three independent healthy controls for the CPT, WCST, and NRA, respectively, and one group of treatment-resistant schizophrenia patients for the MPAs. Additionally, patients from simplex families and patients from multiplex families were used to assess the magnitude of FEP patients’ impairment on the CPT, WCST, and NRA. Results: Among the 80 patients with FEP recruited in this study (58% female, mean age = 25.6 years, mean duration of untreated psychosis = 132 days), the clinical severity was mild to moderate (mean PANSS score = 67.3; mean PSP score = 61.8). Patients exhibited both neurocognitive and niacin response impairments (mean Z-scores: −1.24 for NRA, − 1.06 for undegraded d', − 0.70 for degraded d', − 0.32 for categories achieved, and 0.44 for perseverative errors) but did not show MPAs indicative of treatment resistance. Among these quantitative measures, three of the four neurocognitive indices were correlated with the baseline clinical features, whereas NRA did not show such correlation. Conclusions: This FEP study of Taiwanese patients revealed the presence of neurocognitive performance and niacin response and their different relationships with clinical features, rendering this sample useful for future follow-up and incorporation of multiomics investigation. [ABSTRACT FROM AUTHOR]