Validation of the Chinese Version of Penn Alcohol Craving Scale for Patients With Alcohol Use Disorder.

OBJECTIVE: The Penn Alcohol Craving Scale (PACS) is a five-item, single-dimension questionnaire that is used to measure a patient's alcohol craving. We sought to develop the Chinese version of the PACS (PACS-C) and assess its reliability and validity. METHODS: A total of 160 Taiwanese patients with alcohol use disorder were enrolled in this study. The internal consistency and concurrent validity of the PASC-C with the visual analogue scale (VAS) for craving, the Yale-Brown Obsessive Compulsive Scale for heavy drinking (YBOCS-hd), and the Severity of Alcohol Dependence Questionnaire (SADQ) were assessed. The test-retest reliability of the PASC-C was evaluated 1 day after the baseline measurements. Confirmatory factor analysis (CFA) was performed to examine the psychometric properties of the PACS-C. RESULTS: The PACS-C exhibited good internal consistency (Cronbach's α=0.95) and test-retest reliability (r=0.97). This scale showed high correlations with the VAS (r=0.81) and YBOCS-hd (r=0.81 and 0.79 for the obsession and compulsion subscales, respectively), and moderate correlation with the SADQ-C (r=0.47). Furthermore, CFA results revealed that the PACS-C had good fit indices under various models. CONCLUSION: The PACS-C appears to be a reliable and valid tool for assessing alcohol craving in patients with alcohol use disorder in Taiwan.

GxE interaction effects of HCRTR2 single nucleotide polymorphism and adverse childhood experiences on methamphetamine use disorder.

Background: Methamphetamine use disorder (MUD) is a worldwide health concern. The hypothalamic orexin system regulates stress response and addictive behaviors. The genetic variation in the hypocretin receptor 2 (HCRTR2), rs2653349, is associated with substance use disorder.Objectives: We explored the gene-environment (GxE) interaction of rs2653349 and adverse childhood experiences (ACEs) associated with MUD susceptibility.Methods: Four hundred and one individuals (336 males, 65 females) with MUD and 348 healthy controls (288 males, 60 females) completed a self-report questionnaire evaluating ACEs, encompassing childhood abuse and household dysfunction categories, and were genotyped for SNP rs2653349. Methamphetamine use variables were collected using the Diagnostic Interview for Genetic Studies. We used regression analyses to assess the GxE effect on MUD risk.Results: The MUD group had a comparable genotypic distribution for rs2653349 to the control group, albeit with a higher prevalence and number of types of ACEs, correlating with an increased MUD risk (p < .05). No significant genetic impact of rs2653349 on MUD risk was found. However, we observed a GxE interaction effect between the minor allele of rs2653349 and the number of childhood abuse or household dysfunction types, correlating with a reduced MUD risk (OR = -0.71, p = .04, Benjamini-Hochberg adjusted p = .08 and OR = -0.59, p = .045, Benjamini-Hochberg adjusted p = .09, respectively).Conclusion: HCRTR2 SNP rs2653349 has no significant impact on MUD risk, but ACEs may increase this risk. GxE results suggest that rs2653349 could offer protection against developing MUD in individuals experiencing multiple types of ACEs.

Targeting cravings in substance addiction with transcranial direct current stimulation: insights from a meta-analysis of sham-controlled trials.

Addiction is a substantial health concern; craving-the core symptom of addiction-is strongly associated with relapse. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that reduces cravings by altering cortical excitability and connectivity in brain regions. This systematic review and meta-analysis was conducted (following the PRISMA guidelines) to evaluate the efficacy of tDCS in reducing cravings for substances. Our analysis included 43 randomized, sham-controlled trials involving 1,095 and 913 participants receiving tDCS and sham stimulation, respectively. We analyzed the changes in craving scores and found that tDCS led to a moderate reduction in cravings compared with the sham effects. This effect was particularly pronounced when bilateral stimulation was used, the anodal electrode was placed on the right dorsolateral prefrontal cortex, current intensities ranged from 1.5 to 2 mA, stimulation sessions lasted 20 minutes, and the electrodes size was ≥35 cm². Notably, tDCS effectively reduced cravings for opioids, methamphetamine, cocaine, and tobacco but not for alcohol or cannabis. Our findings indicate tDCS as a promising, noninvasive, and low-risk intervention for reducing cravings for opioids, methamphetamine, cocaine, and tobacco. Additional studies are warranted to refine stimulation parameters and evaluate the long-term efficacy of tDCS in managing substance cravings.

The interplay of childhood trauma, oxytocin, and impulsivity in predicting the onset of methamphetamine use.

BACKGROUND: Childhood trauma is associated with substance use disorders, including methamphetamine use disorder (MUD). Oxytocin, involved in social bonding, stress regulation, and reward processing, may influence addiction vulnerability and impulsivity in individuals with a history of childhood trauma. OBJECTIVE: To investigate the relationships among childhood trauma, oxytocin levels, impulsivity, and the age of first methamphetamine use in individuals with MUD. PARTICIPANTS AND SETTING: The study included 298 male participants (148 individuals with MUD and 150 healthy controls) from both probation offices and psychiatric clinics. METHODS: Childhood trauma was assessed using the Childhood Trauma Questionnaire-Short Form (CTQ-SF), impulsivity with the Barratt Impulsiveness Scale-11 (BIS-11), and plasma oxytocin levels were obtained. RESULTS: Individuals with MUD exhibited higher levels of childhood trauma, impulsivity, and lower plasma oxytocin levels compared to healthy controls. Childhood trauma was associated with a younger age of first methamphetamine use, higher impulsivity, and lower oxytocin levels among individuals with MUD. Plasma oxytocin levels partially mediated the relationship between childhood trauma and both the age of first methamphetamine use and impulsivity. Serial mediation analysis demonstrated that oxytocin levels and impulsivity sequentially mediated the relationship between childhood trauma and the age of first methamphetamine use. CONCLUSIONS: The findings reveal the complex interplay among childhood trauma, oxytocin, impulsivity, and methamphetamine use, emphasizing the importance of considering these factors in prevention and intervention strategies for MUD. Future research should explore oxytocin and impulsivity-focused interventions to mitigate the effects of childhood trauma and reduce MUD development risk.

Quality of life and associated factors of heroin-dependent patients receiving methadone and buprenorphine maintenance treatment.

AIM: Although studies in Western countries have investigated the quality of life (QoL) of heroin users, limited research on this topic has been conducted in Asia. The present study assessed QoL in patients with heroin dependence receiving medications to treat opioid use disorder. METHODS: We performed a cross-sectional study of patients with heroin dependence receiving methadone and buprenorphine treatment. The demographic and substance use variables of patients receiving methadone and buprenorphine were compared. The Chinese Health Questionnaire (CHQ-12), Obsessive Compulsive Drug Use Scale (OCDUS), and World Health Organization Quality of Life Short Form Taiwan version (WHOQOL-BREF-T) were administered to measure patient mental health problems, addiction severity, and QoL, respectively. Multivariate regression was used to identify the factors associated with QoL. RESULTS: A total of 149 patients receiving methadone and 31 receiving buprenorphine completed the questionnaires. Individuals in the buprenorphine group were more likely to be married (p = 0.024) or employed (p = 0.024), have a higher educational level (p = 0.013), have lower drug craving (OCDUS: p = 0.035), or have higher QoL (WHOQOL-BREF-T: p = 0.004) than those in the methadone group. After adjustment for other variables, employment was positively associated with the physical, psychological, and environmental domains of QoL. Receiving buprenorphine treatment (p = 0.032) and longer treatment duration (p = 0.016) were associated with higher psychological QoL. CONCLUSION: Several factors were associated with QoL in patients with heroin dependence. Some measures may improve their QoL, such as reducing employment barriers, improving treatment adherence, or increasing accessibility to buprenorphine treatment.

Unfavorable cancer mortality-to-incidence ratios in patients with schizophrenia: A nationwide cohort study in Taiwan, 2000-2019.

OBJECTIVES: Studies on cancer incidence and mortality in patients with schizophrenia have reported inconsistent findings. In this study, we simultaneously investigated cancer incidence and mortality in patients with schizophrenia and evaluated the cancer mortality-to-incidence ratio (MIR), which is rare in the literature. METHODS: From the Taiwan National Health Insurance Database, we collected the data of 107,489 patients who received a diagnosis of schizophrenia between 2000 and 2019. Data regarding cancer incidence and mortality were obtained from the Taiwan Cancer Registry and National Mortality Database, respectively. In total, 3881 incident cancer cases and 2288 cancer mortality cases were identified. Standardized incidence ratios (SIRs), mortality rate ratios (MRRs), and MIRs were compared between patients with schizophrenia and the general population. RESULTS: The overall rate of cancer incidence was slightly lower (SIR: 0.95; 95% confidence interval [CI]: 0.92-0.98; p < 0.001) and that of cancer mortality was higher (MRR: 1.29; 95% CI: 1.23-1.3; p < 0.001) in patients with schizophrenia than in the general population. The MIR for overall cancer was significantly higher in the patients with schizophrenia. The relative MIR (MIR of patients with schizophrenia divided by that of the general population) was 1.36 (95% CI: 1.30-1.42). CONCLUSION: The MIR was significantly higher in the patients with schizophrenia than in the general population, indicating the possible presence of healthcare disparities. Additional studies are required to investigate the potential association between the significantly higher MIR in patients with schizophrenia and healthcare disparities.

A smartphone-based support system coupled with a bluetooth breathalyzer in the treatment of alcohol dependence: A 12-week randomized controlled trial.

Background: Our prior open trial showed the feasibility of a smartphone-based support system coupled with a Bluetooth breathalyzer (SoberDiary) in assisting recovery for patients with alcohol dependence (AD). In this 24-week follow-up study, we further explored the efficacy of supplementing SoberDiary to treatment as usual (TAU) over 12 weeks of intervention and whether the efficacy persisted in the post-intervention 12 weeks. Methods: 51 patients who met the DSM-IV criteria of AD were randomly assigned to the technological intervention group (TI group, receiving technology intervention of SoberDiary plus TAU, n = 25) or those receiving only TAU (TAU group, n = 26). After 12 weeks of intervention (Phase I), all participants were followed for another post-intervention 12 weeks (Phase II). We collected the drinking variables and psychological assessment data every 4 weeks (i.e., weeks 4, 8, 12, 16, 20, and 24). In addition, the cumulative abstinence days and retention rates were recorded. We used mixed-model analysis to compare the difference in outcomes between groups. Results: In Phase I or Phase II, we did not find differences in drinking variables, alcohol craving, depression, or anxiety severity between the two groups. However, the TI group showed greater self-efficacy for drinking refusal in Phase II than the TAU group. Conclusions: Although our system (SoberDiary) did not demonstrate benefits in drinking or emotional outcomes, we found the system holds promise to enhance self-efficacy on drinking refusal. Whether the benefit in promoting self-efficacy persists longer than 24 weeks requires further investigation.

Risk factors for relapse among methamphetamine users receiving a joint legal-medical treatment program as a diversion intervention: A one-year follow-up study.

BACKGROUND: Methamphetamine (METH) is a Schedule II illicit drug in Taiwan. A 12-month legal-medical joint intervention program has been developed for first-time METH offenders during deferred prosecution. Risk factors associated with METH relapse use among these individuals were unknown. METHODS: We enrolled a total of 449 METH offenders referred by the Taipei District Prosecutor's Office to Taipei City Psychiatric Center. The study defines relapse as having any positive urine toxicology result or self-report of METH use during 12-month treatment. We compared demographic and clinical variables between a relapse group and nonrelapse group and used a Cox proportional hazards model to determine variables associated with time to relapse. RESULTS: Of all participants, 37.8 % relapsed to use METH and 23.2 % were noncompleters in the one-year follow-up. Compared to the nonrelapse group, the relapse group had lower educational attainment, more severe psychological symptoms, longer duration of METH use, higher odds of polysubstance use, higher craving severity, and higher odds of positive baseline urine. The Cox analysis revealed individuals with positive urine results and higher craving severity at baseline were at higher risks of METH relapse (hazard ratio [95 % CI]: 3.85 [2.61-5.68] and 1.71 [1.19-2.46], respectively, p < 0.001). Baseline positive urine results and high craving could also predict a shorter length of time to relapse than their respective counterparts. CONCLUSIONS: Positive urine screening for METH at baseline and high craving severity are two indicators of an increased risk of drug relapse. Tailored treatment plans incorporating these findings to prevent relapse are warranted in our joint intervention program.

Sex-specific risk profiles for suicide mortality in bipolar disorder: incidence, healthcare utilization and comorbidity.

BACKGROUND: Evidence on sex-specific incidence and comorbidity risk factors of suicide among patients with bipolar disorder is scarce. This study investigated the sex-specific risk profiles for suicide among the bipolar disorder population in terms of incidence, healthcare utilization and comorbidity. METHODS: Using data from the Taiwan National Health Insurance Research Database between 1 January 2000 and 31 December 2016, this nationwide cohort study included patients with bipolar disorder (N = 46 490) and individuals representative of the general population (N = 185 960) matched by age and sex at a 1:4 ratio. Mortality rate ratios (MRRs) of suicide were calculated between suicide rates of bipolar disorder cohort and general population. In addition, a nested case-control study (1428 cases died by suicide and 5710 living controls) was conducted in the bipolar disorder cohort to examine the sex-specific risk of healthcare utilization and comorbidities. RESULTS: Suicide risk was considerably higher in the cohort (MRR = 21.9) than in the general population, especially among women (MRR = 35.6). Sex-stratified analyses revealed distinct healthcare utilization patterns and physical comorbidity risk profiles between the sexes. Although female patients who died by suicide had higher risks of nonhypertensive cardiovascular disease, pneumonia, chronic kidney disease, peptic ulcer, irritable bowel syndrome, and sepsis compared to their living counterparts, male patients who died by suicide had higher risks of chronic kidney disease and sepsis compared to the living controls. CONCLUSIONS: Patients with bipolar disorder who died by suicide had sex-specific risk profiles in incidence and physical comorbidities. Identifying these modifiable risk factors may guide interventions for suicide risk reduction.

Incidence of and risk factors for alcohol dependence in bipolar disorder: A population-based cohort and nested case-control study.

OBJECTIVES: Although alcohol dependence is highly prevalent in patients with bipolar disorder, the causal relationship is not yet well-established. This study estimated the incidence of alcohol dependence in a nationwide bipolar disorder cohort and examined risk factors for alcohol dependence. METHODS: Patients aged 15-65 years with consistent bipolar disorder who had their first psychiatric admission between 1999 and 2012 (n = 21,791) were enrolled from the National Health Insurance Research Database in Taiwan. We calculated the adjusted incidence rate ratio of alcohol dependence in the bipolar cohort relative to the general population after stratification by age and sex. In the nested case-control study, we included patients with incident alcohol dependence as cases and four age- and sex-matched controls for each case to analyze health care utilization, comorbidities and concomitant medications between them. RESULTS: We identified 1261 patients with bipolar disorder with incident alcohol dependence. Relative to the general population, the adjusted incidence rate ratio of alcohol dependence was 9.20 in the bipolar cohort. All adjusted incidence rate ratios were high across all age subgroups. Cases had higher psychiatric and nonpsychiatric health care utilization than did controls. Multivariate analysis revealed that cases tended to have cardiovascular disease, diabetes mellitus, chronic hepatic disease, pneumonia and delirium before alcohol dependence diagnosis. Cases had higher psychiatric comorbidities, namely drug-induced mental disorders, anxiety disorder, personality disorder, adjustment disorder and sleep disorder. CONCLUSION: The bipolar cohort had a higher incidence of alcohol dependence. We identified specific groups with a high risk of alcohol dependence. Additional strategies for early detection, treatment and intervention for alcohol dependence should be developed.

Premature death and causes of death among patients with panic disorder and comorbid psychiatric disorders: A nationwide cohort study.

OBJECTIVES: Panic disorder (PD) is associated with high psychiatric and physical comorbidity, but the cause of mortality has not been well studied. This study investigated mortality rates and causes of death in an Asian cohort with PD. METHODS: We enrolled a nationwide retrospective cohort of 298,466 persons diagnosed with PD from January 1, 2001, to December 31, 2016. Each cohort member was matched with a comparison one randomly selected from the general population with the same sex, age at entry, and birth year. The data of both the PD cohort and the comparison group were linked with the national mortality database to obtain each individual's mortality status. We used mortality rate ratios (MRRs) to compare mortality risks between the patients with PD and the general population. Stratified analysis of mortality risks was performed based on sex and psychiatric comorbidities. RESULTS: PD was associated with a slightly increased mortality risk (MRR, 1.14 [99% CI, 1.11-1.17]). The risk of unnatural death (MRR, 2.83 [99% CI, 2.59-3.10]) was significantly higher among the individuals with PD than among the general population, whereas the risk of overall natural death across all categories was not (MRR, 1.01 [99% CI, 0.98-1.04]). The mortality risk was the highest for suicide (MRR, 4.94 [99% CI, 4.32-5.72]) and was higher in women (MRR, 6.37 [99% CI, 5.25-7.96]) than in men (MRR, 3.77 [99% CI, 3.14-4.64]). Comorbid substance use disorders increased the risk of mortality from natural (MRR, 3.23 [99% CI, 2.59-4.14]) and unnatural (MRR, 9.45 [99% CI, 6.29-17.85]) causes. CONCLUSION: PD was associated with increased all-cause mortality, especially suicide. Substance use further increased mortality risk in persons with PD. Targeted treatment for substance use and suicide prevention are essential among persons with PD.

Increased medical utilization and psychiatric comorbidity following a new diagnosis of methamphetamine use disorder.

Background: Evidence of patterns of medical utilization and distribution of comorbidities among individuals using methamphetamine remains limitedObjective: This study aims to investigate changes in medical utilization and comorbidities before and after a diagnosis of methamphetamine use disorder.Methods: A total of 3321 cases (79% were male) of methamphetamine use disorder between January 1, 1996, and December 31, 2012, were identified from Psychiatric Inpatient Medical Claims database in Taiwan. Information was collected on demographics, diagnoses, and medical utilizations. The date of newly diagnosed with methamphetamine use disorder was defined as the baseline. Mirror-image study design was used to compare changes in medical utilization and comorbidities between the pre-baseline period (within 1 year before diagnosis) and the post-baseline period (within 1 year after diagnosis). Conditional logistic regression was used to estimate changes in medical utilization and comorbidities.Results: Most cases (77%) were first identified in a psychiatric department. There is a significant increase (P < .001) in psychiatric admission (odds ratio[OR] = 2.19), psychiatric emergency visits (OR = 1.31), and psychiatric outpatient visits (OR = 1.15) after diagnosis. Multivariable analysis revealed significantly increased risks (P < .001) of non-methamphetamine drug induced mental disorders (adjusted OR[aOR] = 29.47), schizophrenia (aOR = 2.62), bipolar disorder (aOR = 2.14), organic mental disorder (aOR = 1.82), and upper respiratory tract infection (aOR = 2.03) after diagnosis.Conclusions: We found significant increases of medical utilization and psychiatric comorbidities after diagnosed with methamphetamine use disorder. These findings may reflect the problem of delayed diagnosis and treatment. Enhancement of early identification of methamphetamine use disorder in general practice is required for early intervention and decreased subsequent morbidities.

Healthcare utilization and psychiatric and physical comorbidities before suicide mortality in patients with methamphetamine use disorder: A nationwide case-control study.

BACKGROUND: Since the late 1990s, methamphetamine use has become a considerable public health concern. Despite high suicide rates among methamphetamine users, studies exploring medical utilization and psychiatric and physical comorbidities before suicide are scant. We aim to examine the pattern of medical utilization and distribution of comorbidities shortly before suicide in methamphetamine users who died of suicide and compared these data with those of living methamphetamine users. METHODS: From Taiwan's National Health Insurance Research Database, we identified the cohort with methamphetamine use disorder (n = 23,248) between January 1, 2001, and December 31, 2005. We identified 5972 deceased patients (of whom 745 died of suicide) by linking each patient with the national mortality database during the study period. By conducting a nested case-control study with risk-set sampling, from the methamphetamine cohort, we selected four age- and sex-matched controls for each patient who died of suicide (cases). We applied conditional logistic regression to investigate differences in medical utilization and physical and psychiatric comorbidities between cases and controls. RESULTS: Cases had higher medical utilization within 3 months before suicide, particularly in the departments of psychiatry, internal medicine, emergency, and family practice. Cases had higher risks of physical comorbidities, including pneumonia and renal disease, and psychiatric comorbidities, including depressive disorder, sleep disorder, drug-induced mental disorder, schizophrenia, and bipolar disorder. CONCLUSIONS: The findings of increased medical utilization and the higher risks of physical and psychiatric comorbidities in cases are crucial for developing specific interventions to prevent suicide in this patient population.

Increased Nectin-4 levels in chronic ketamine abusers and the relationship with lower urinary tract symptoms.

Persistent ketamine use causes susceptibility to addiction and bladder toxicity. We examined the association of lower urinary tract symptoms and levels of Nectin-4, a member of the cell adhesion molecules that is essential for maintaining the urothelium barrier in chronic ketamine abusers. We measured the plasma levels of Nectin-4 in 88 patients with ketamine dependence and 69 controls. Patients with ketamine dependence were assessed for ketamine use variables, psychological symptoms, and lower urinary tract symptoms. We found Nectin-4 levels were increased in ketamine-dependent patients compared to the controls (p < 0.0001). Patients with urinary tract symptoms exhibited lower Nectin-4 levels than those without (p = 0.021). Our results suggest an up-regulation of Nectin-4 following chronic and heavy ketamine use. Patients with ketamine dependence with a compromised upregulation of Nectin-4 are likely to have more severe urinary tract symptoms. The mechanisms underlying the involvement of Nectin-4 in ketamine addiction and bladder toxicity warrant future investigation.

Examining factors associated with postintervention recidivism in DUI repeat offenders after alcohol treatment: One-year follow-up study.

Taiwan has deemed driving under the influence of alcohol (DUI) to be criminal, and offenders are subjected to fines and jail penalties without being offered alcohol-related treatment, although alcohol use problems are prevalent in this population. We followed the recidivism records of DUI repeat offenders for one year after they had received a newly established legal-medical joint intervention program for alcohol treatment and examined factors related to postintervention recidivism. In this study, 231 DUI repeat offenders with alcohol use problems screened out by the Alcohol Use Disorder Identification Test were referred from the prosecutors' office to one psychiatric hospital for SBIRT-based alcohol treatment. We divided the participants into two groups based on the official recidivism records within the year following the end of treatment. The study used a Cox proportional hazards model to examine the hazard ratio of the baseline clinical characteristics and intervention duration for post-treatment recidivism. The study used generalized estimation equation models to examine changes in psychological symptoms and drinking behaviors over time. We found that participants who recidivated in the next year after intervention did not differ from those without recidivism records in all measurements except for the length of duration they stayed in treatment. Survival analysis determined that participants who had received the intervention for >4 months showed significantly lower rates of one-year postintervention recidivism rates The study participants showed improved psychological symptoms and drinking behaviors during the follow-up period. In conclusion, adequate duration of alcohol treatment is a significant factor associated with a lower risk of postintervention recidivism. The results provide some insight into the design of a collaborative program between legal and medical systems to reduce DUI recidivism and improve mental health of DUI repeat offenders.

All-cause and suicide mortality among people with methamphetamine use disorder: a nation-wide cohort study in Taiwan.

BACKGROUND AND AIMS: Although methamphetamine use is a serious public health problem, large-scale cohort studies assessing methamphetamine-related mortality are scant. This study investigated all-cause mortality and suicide methods in people with methamphetamine use disorder. DESIGN: A cohort record-linkage study using data from Taiwan's National Health Research Institute Database (NHIRD) linked to Taiwan's National Death Certification System. SETTING: Taiwan. PARTICIPANTS: A total of 23 248 individuals with methamphetamine use disorder between 1 January 2001 and 31 December 2005. MEASUREMENTS: The outcome variables included mortality rates and standardized mortality ratios (SMRs) for all causes of death and for each suicide method. FINDINGS: Compared with the general population, the current cohort had an increased all-cause mortality (SMR = 5.4), with the SMR for unnatural causes (14.8) higher than that for natural causes (7.5). Among all causes of death, suicide had the highest SMR (16.3), followed by neurological diseases (9.7). Among the methods of choice for suicide, drug overdose had the highest SMR (24.9). The incidence of charcoal burning and hanging was significantly higher in men and that of jumping from a high place was significantly higher in women. CONCLUSION: People in Taiwan with methamphetamine use disorder appear to have a significantly increased all-cause mortality rate compared with the general population, with suicide having the highest contribution, particularly suicide via drug overdose. The methods of choice for suicide revealed distinct patterns between men and women.

Incidence and method of suicide mortality in patients with schizophrenia: a Nationwide Cohort Study.

PURPOSE: Suicide is a leading cause of death in patients with schizophrenia. This nationwide cohort study investigated the incidence of each suicide method in patients with schizophrenia compared with the general population. METHODS: In total, records of 174,039 patients with schizophrenia were obtained from the National Health Insurance Research Database in Taiwan from 2001 to 2016. This schizophrenia cohort was linked with the national mortality database, and 26,926 patients died during this follow-up period. Of the deceased, 3033 had died by suicide. Univariate Cox regression was used to estimate the demographic variables associated with suicide. We estimated the difference in the proportion of each suicide method used in patients with schizophrenia compared with the general population. The incidence and standardized mortality ratio (SMR) of each suicide method were calculated and stratified based on sex. RESULTS: Patients aged 25-34 years exhibited the highest suicide risk. Compared with the general population, patients with schizophrenia were more likely to commit suicide by jumping and drowning and less likely to use charcoal-burning and hanging. Women showed a higher incidence of suicide by drowning and jumping than did men. Comorbidity with substance use disorders (SUDs) was associated with a high suicide SMR (26.9, 95% confidence interval [CI] = 23.4-28.9), particularly for suicide by jumping (61.2, 95% CI = 48.3-76.3). CONCLUSIONS: Patients with schizophrenia had higher suicide rates for all methods than did the general population. Suicide method differed based on sex. Patients with SUDs exhibit a high SMR for each suicide method and warrant intensive clinical attention.

Age Effect on Incidence, Physical, and Psychiatric Comorbidity for Sudden Cardiac Death in Schizophrenia: Effet de l'âge sur l'incidence, la comorbidité physique et psychiatrique de la mort cardiaque subite dans la schizophrénie.

OBJECTIVE: The pathogenesis of sudden cardiac death may differ between younger and older adults in schizophrenia, but evidence remains scant. This study investigated the age effect on the incidence and risk of the physical and psychiatric comorbidity for sudden cardiac death. METHODS: Using 2000 to 2016 data from the Taiwan National Health Insurance Research Database and Department of Health Death Certification System, we identified a national cohort of 170,322 patients with schizophrenia, 1,836 of whom had a sudden cardiac death. Standardized mortality ratios (SMRs) were estimated. Hazard ratios and population attributable fractions of distinctive comorbidities for sudden cardiac death were assessed. RESULTS: The SMRs of sudden cardiac death were all >1.00 across each age group for both sexes, with the highest SMR in male patients aged <35 years (30.88, 95% CI: 26.18-36.18). The fractions of sudden cardiac death attributable to hypertension and congestive heart failure noticeably increased with age. By contrast, the fraction attributable to drug-induced mental disorder decreased with age. Additionally, chronic hepatic disease and sleep disorder increased the risk of sudden cardiac death in patients aged <35 years. Dementia and organic mental disorder elevated the risk in patients aged between 35-54 years. Ischemic heart disease raised the risk in patients aged ≥55 years. CONCLUSIONS: The risk is increased across the lifespan in schizophrenia, particularly for younger male patients. Furthermore, physical and psychiatric comorbidities have age-dependent risks. The findings suggest that prevention strategies targeted toward sudden cardiac death in patients with schizophrenia must consider the age effect.

High Risk and Trajectories of Physical Illnesses before the Diagnosis of Bipolar Disorder.

OBJECTIVE: The authors investigated the distributions and trajectories of physical illnesses preceding the diagnosis of bipolar disorder with comparison to schizophrenia and general populations. METHODS: Using data from the Taiwan National Health Insurance Research Database entered from 1996 to end of 2012, we identified 13,079 patients newly diagnosed as having bipolar disorder between the age of 13 and 40 years (ie, cases). For each case with bipolar disorder, two age- and sex- and diagnosis year- schizophrenia comparisons (n=26,158)(n=26,158) and four age- and sex-matched comparisons representing the general population (n=52,316)(n=52,316) were randomly selected from the cohort. Multivariate conditional logistic regression analyses were conducted to estimate the risk of physical illness before the diagnosis (index date). Variables exhibiting a powerful association (p<0·001) were retained in the final model. RESULTS: During the year before diagnosis, patients with newly diagnosed bipolar disorder had a higher risk of numerous physical illnesses across the cardiovascular, respiratory, gastrointestinal, endocrine/metabolic, and musculoskeletal/integument systems compared with those with schizophrenia and the general population. Trends in the risk of specific physical illnesses, mainly hypertension, heart disease, asthma, ulcer disease, hyperlipidemia, and connective tissue disease, were increased across the 3-year prodromal phase of bipolar disorder relative to schizophrenia. CONCLUSIONS: Intriguingly, physical illnesses before the diagnosis of bipolar disorder are pervasive with higher risk. Moreover, the trajectories of physical illnesses markedly differ from those of schizophrenia before full manifestation.