Suicide Attempts After a Diagnosis of Polycystic Ovary Syndrome : A Cohort Study.

BACKGROUND: Limited evidence exists about suicide risk in persons with polycystic ovary syndrome (PCOS). OBJECTIVE: To assess suicide risk in persons with PCOS, accounting for psychiatric comorbid conditions and age group. DESIGN: Cohort study. SETTING: Data from the Taiwanese nationwide database from 1997 to 2012. PATIENTS: A cohort of 18 960 patients diagnosed with PCOS, each matched with control participants in a 1:10 ratio on the basis of age, psychiatric comorbid conditions, urbanization level, and income. Suicide attempts were evaluated using Cox regression models. MEASUREMENTS: Suicide risk with hazard ratios (HRs). RESULTS: Participants with PCOS had a notable 8.47-fold increase in risk for suicide attempt compared with the control group (HR, 8.47 [95% CI, 7.54 to 9.51]), after adjustment for demographic characteristics, psychiatric comorbid conditions, Charlson Comorbidity Index scores, and frequency of all-cause clinical visits. The elevated risk was evident across the adolescent (HR, 5.38 [CI, 3.93 to 7.37]), young adult (<40 years; HR, 9.15 [CI, 8.03 to 10.42]), and older adult (HR, 3.75 [CI, 2.23 to 6.28]) groups. Sensitivity analyses involving the exclusion of data from the first year or the first 3 years of observation yielded consistent results. LIMITATION: Potential underestimation of PCOS and mental disorder prevalence due to use of administrative claims data; lack of clinical data, such as body mass index and depressive symptoms; and no assessment of a confounding effect of valproic acid exposure. CONCLUSION: This study underscores the heightened risk for suicide attempt that persons with PCOS face, even after adjustment for demographics, psychiatric comorbid conditions, physical conditions, and all-cause clinical visits. This suggests the importance of routine monitoring of mental health and suicide risk in persons diagnosed with PCOS. PRIMARY FUNDING SOURCE: Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and Ministry of Science and Technology of Taiwan.

The optimal antithrombotic strategy for post-stroke patients with atrial fibrillation and extracranial artery stenosis-a nationwide cohort study.

BACKGROUND: In post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies. METHODS: This study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone. RESULTS: The risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052-1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454-0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529-0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478-0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231-1.880), ICH (aHR 2.045, 95% CI 1.329-3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB. CONCLUSIONS: For post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy.

Risk of traumatic brain injury among patients with ADHD and their unaffected siblings.

BACKGROUND: As the relationship between attention deficit hyperactivity disorder (ADHD) and traumatic brain injury (TBI) is gaining increasing attention, the TBI risk in patients with ADHD, unaffected siblings of ADHD probands, and non-ADHD controls remains unclear. METHODS: Overall, 18,645 patients with ADHD, 18,880 unaffected siblings of ADHD probands, and 188,800 age-/sex-matched controls were followed up from enrollment to the end of 2011. The cases of TBI and TBI requiring hospitalization were identified during follow-up. RESULTS: Patients with ADHD (hazard ratio [HR]: 1.57) and unaffected siblings (HR: 1.20) had an increased risk of any TBI compared with non-ADHD controls. Surprisingly, the likelihood of developing TBI requiring hospitalization during follow-up was higher in the unaffected siblings group (HR: 1.21) than in the control group, whereas it was lower in the ADHD probands group (HR: 0.86). CONCLUSIONS: Patients with ADHD and unaffected siblings of ADHD probands were more likely to develop any TBI during follow-up than controls. Unaffected siblings of patients with ADHD exhibited the highest risk of subsequent TBI requiring hospitalization compared with patients with ADHD and healthy controls. Therefore, TBI risk in patients with ADHD and their unaffected siblings would require further investigation. IMPACT: ADHD diagnosis and ADHD trait are associated with risk of traumatic brain injury (TBI). Both patients with ADHD and their unaffected siblings were more likely to develop TBI during the follow-up compared with the control group. TBI requiring hospitalization occurred more in the sibling group than in the proband group. TBI risk should be closely monitored among unaffected siblings of patients with ADHD.

Risk of autoimmune diseases after post-traumatic stress disorder: a nationwide cohort study.

This longitudinal study aimed to investigate the risk of subsequent autoimmune disease in patients with post-traumatic stress disorder (PTSD) in Asian population. Between 2002 and 2009, we enrolled 5273 patients with PTSD and 1:4 matched controls from the National Health Insurance Database of Taiwan, and followed up the patients until December 31, 2011, or death. The investigated autoimmune diseases included thyroiditis, lupus, rheumatic arthritis, inflammatory bowel disease, Sjogren's syndrome, dermatomyositis, and polymyositis. The Cox regression model was used to estimate the risk of developing autoimmune diseases, with adjustment for demographics and psychiatric and medical comorbidities. Furthermore, we examined the psychiatric clinics utility of patients with PTSD indicating the severity of PTSD in association with autoimmune diseases. After adjusting for confounders, patients with PTSD had a 2.26-fold higher risk of developing any autoimmune diseases (reported as hazard ratios with 95% confidence intervals: 1.82-2.80) than the controls. For specific autoimmune diseases, patients with PTSD had a 2.70-fold higher risk (1.98-3.68) of thyroiditis, a 2.95-fold higher risk (1.20-7.30) of lupus, and a 6.32-fold higher risk (3.44-11.60) of Sjogren's syndrome. Moreover, the PTSD severity was associated with the risk of autoimmune diseases in a dose-dependent manner. The patient with the highest psychiatric clinics utility was associated with an 8.23-fold higher risk (6.21-10.90) of any autoimmune diseases than the controls. Patients with PTSD had an increased risk of autoimmune diseases, and such risk was associated with the severity of PTSD in a dose-dependent manner. However, the present study did not provide a direct effect between PTSD and autoimmune diseases, but rather an association. Further studies are warranted to examine the underlying pathophysiological mechanisms.

Exposure to psychotropic drugs and breast cancer risk in patients with bipolar disorder and major depressive disorder: a nested case-control study.

Breast cancer is one of the most prevalent and serious types of cancer globally. Previous literature has shown that women with mental illness may have an increased risk of breast cancer, however whether this risk is associated with the use of psychotropic drugs has yet to be elucidated. This study aimed to assess such risk among women with major depressive disorder (MDD) and bipolar disorder (BD). A nested case-control study design was used with data obtained from the Taiwan National Health Insurance Research Database. Logistic regression analysis with adjustments for demographic characteristics, medical and mental comorbidities, and all-cause clinical visits was performed to estimate the risk of breast cancer according to the cumulative defined daily dose (cDDD) of psychotropic drugs. The study included 1564 women with MDD or BD who had breast cancer, and 15,540 women with MDD or BD who did not have breast cancer. After adjusting for important confounders, the long-term use of valproic acid (odds ratio, 95% confidence interval: 0.58, 0.39-0.56, cDDD ≥ 365), citalopram (0.58, 0.37-0.91, cDDD 180-365), and sertraline (0.77, 0.61-0.91, cDDD ≥ 365) was associated with a lower risk of breast cancer compared to a cDDD < 30. The short-term use of fluvoxamine (0.82, 0.69-0.96, cDDD 30-180), olanzapine (0.54, 0.33-0.89, cDDD 30-179), risperidone (0.7, 0.51-0.98, cDDD 30-179), and chlorpromazine (0.48, 0.25-0.90, cDDD 30-179) was associated with a lower risk of breast cancer. We found no evidence of an increased risk of breast cancer in patients with MDD or BD receiving psychotropic drugs.

Elevated risk of sexually transmitted infections among adolescents and young adults with borderline personality disorder: a retrospective longitudinal nationwide population-based study.

In this study, we examined the risk of sexually transmitted infections (STIs) among adolescents and young adults (AYAs) with borderline personality disorder (BPD). A total of 4649 AYAs with BPD and 46,490 age-, sex-, and socioeconomic-matched controls without BPD were enrolled from the National Health Insurance Research Database of Taiwan from 2001 to 2009 and were followed up until the end of 2011. Participants who contracted any STI during the follow-up period were identified. Cox regression analysis was conducted to examine the risk of contracting any STI among both patients and controls. A total of 4649 AYAs with BPD and 46,490 age-, sex-, and socioeconomic-matched controls without BPD were enrolled from the National Health Insurance Research Database of Taiwan from 2001 to 2009 and were followed up until the end of 2011. Participants who contracted any STI (ICD-9-CM code 042, 091-097, 087.11, 078.8, 078.88, 131, and 054.1) during the follow-up period were identified. Cox regression and sub-analyses stratified by sex, age, psychiatric comorbidity subgroups, and psychotropic medication usage were conducted to assess STI risk. AYAs with BPD were at a higher risk of contracting any STI (hazard ratio [HR] = 50.79, 95% confidence interval [CI] = 33.45-77.11) in comparison with controls, including HIV, syphilis, genital warts, gonorrhea, chlamydia, trichomoniasis, and genital herpes. The association of BPD with an increased risk of any STI was prevalent in both sexes, adolescents, and young adult patients. BPD with or without psychiatric comorbid subgroup were all associated with an elevated risk of contracting any STI relative to the control group. AYAs with BPD are highly susceptible to contracting STIs. Future studies should examine the role of the core symptoms of BPD, sexual orientation, risky sex behaviors, depressive and anxiety symptoms, and substance use before sex in the risk of STIs among AYAs with BPD.

Longitudinal study on all-cause and suicide mortality among individuals with attention deficit hyperactivity disorder.

BACKGROUND: Previous research has linked attention deficit hyperactivity disorder (ADHD) with an increased risk of all-cause mortality, primarily owing to unnatural causes such as accidents and suicides. This increase may be attributable to the co-occurrence of major psychiatric disorders, including schizophrenia (SCZ), bipolar disorder (BD), major depressive disorder (MDD), autism spectrum disorder (ASD), anxiety disorders, substance use disorders (SUDs), and personality disorders (PDs). This study examined the all-cause and specific-cause mortality rates in individuals with ADHD and the influence of psychiatric comorbidities. METHODS: Between 2003 and 2017, 1.17 million individuals were enrolled in the study, of which 233,886 received a diagnosis of ADHD from the Taiwan's National Health Insurance Research Database. A 1:4 sex- and birth year-matched control group without ADHD was also included. Hazard ratios (HRs) for mortality rates were estimated between groups after adjusting for demographic data. RESULTS: During the follow-up period, 781 individuals with ADHD died. The HR for all-cause mortality was 1.45 (95% confidence interval [CI]: 1.30-1.61), largely owing to unnatural causes, particularly suicide. Suicide rates were particularly high in individuals with ADHD and psychiatric comorbidities: the HRs for suicide were 47.06 in ADHD with SUDs (95% CI: 6.12-361.99), 32.02 in ADHD with SCZ (7.99-128.29), 23.60 in ADHD with PDs (7.27-76.66), 10.11 in ADHD with anxiety disorders (5.74-17.82), 9.30 in ADHD with BD (4.48-19.33), 8.36 in ADHD with MDD (5.66-12.35), and 6.42 in ADHD with ASD (1.83-22.53) relative to ADHD only. DISCUSSION: ADHD was associated with increased mortality rates, primarily owing to suicide. The presence of major psychiatric comorbidities was associated with a further increase in suicide mortality risk.

Sexually transmitted infection and teenage pregnancy in adolescents having parents with schizophrenia: a retrospective cohort study of 64,350 participants.

BACKGROUND: The risks of sexually transmitted infections (STIs) and teenage pregnancy in the offspring of parents with schizophrenia remain unknown. METHODS: From the Taiwan National Health Insurance Research Database, 5,850 individuals born between 1980 and 1999 having any parent with schizophrenia and 58,500 age-, sex-, income- and residence-matched controls without parents with severe mental disorders were enrolled in 1996 or on their birthdate and followed up to the end of 2011. Those who contracted any STI or became pregnant in adolescence during the follow-up period were identified. RESULTS: Cox regression analyses demonstrated that offspring of parents with schizophrenia (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.02-1.44), especially daughters (HR: 1.30, 95% CI: 1.06-1.58), were more likely to contract any STI later in life than the control comparisons. In addition, daughters of parents with schizophrenia had an elevated risk of being pregnant in their adolescence (HR: 1.47, 95% CI: 1.29-1.67) compared with those having no parents with severe mental disorders. DISCUSSION: The positive relationship between parental schizophrenia and offspring STIs and teenage pregnancy necessitates clinicians and public health officers to closely monitor the sexual health in the offspring of parents with schizophrenia so that optimal and prompt preventive measures can be taken in the at-risk group.

Parental mental disorders in patients with comorbid schizophrenia and obsessive-compulsive disorder: a nationwide family-link study.

Schizophrenia is highly comorbid with obsessive-compulsive disorder (OCD); both conditions share numerous pathophysiological etiologies. We, thus, examined the risk of mental disorders in the parents of probands with schizophrenia, OCD, or both conditions. Between 2001 and 2011, we enrolled a nationwide cohort of 69,813 patients with schizophrenia, OCD, or both. The control cohort included 698,130 individuals matched for demographics. Poisson regression models were employed to examine the risk of six mental disorders in their parents, including schizophrenia, bipolar disorder, depressive disorder, OCD, alcohol use disorder, and substance use disorder. We stratified patients into schizophrenia-only, OCD-only, and dual-diagnosis groups, and the dual-diagnosis group was further divided into schizophrenia-first, OCD-first, and simultaneously diagnosed groups. Compared with controls, the schizophrenia, OCD, and dual-diagnosis groups had higher risks for the six mental disorders in their parents (range of odds ratio [OR] 1.50-7.83). The sub-analysis of the dual-diagnosis group showed that the schizophrenia-first, OCD-first, and simultaneously diagnosed groups had higher odds for schizophrenia, bipolar disorder, depressive disorder, and OCD (range of OR 1.64-6.45) in their parents than the control group; the simultaneously diagnosed and OCD-first diagnosed groups had a higher odds of parental substance use disorder, while the schizophrenia-first diagnosed group had a higher odds of parental alcohol use disorder. The interrelationship between OCD and schizophrenia is linked to bipolar disorder, depressive disorder, alcohol use disorder, and substance use disorder. The results have implications for mental health policy and future research.

Diagnostic conversion to bipolar disorder among adolescents and young adults with major depressive disorder: a nationwide longitudinal study.

Although several studies have examined a diagnostic conversion from major depressive disorder (MDD) to bipolar disorder (BD), only a few studies specifically focused on adolescents and young adults who are at the peak ages of BD onset. Data from participants (N = 130,793) aged 10-29 years who were diagnosed with MDD were extracted from the Taiwan National Health Insurance Research Database. We applied demographic analyses, survival analysis, Aalen Johansen curves, and Cox regression, investigating the diagnostic conversion rate and factors that were most or less predictive of conversion. Among the adolescents and young adults with MDD, the number of participant conversion subsample is 14,187 and the conversion rate was 13.80% (95% confidence interval: 13.54-14.06%) during the 11-year follow-up. The conversion rate was highest in the first year (4.50%; 4.39-4.61%) and decreased over time. The significant predictors were younger age of diagnosis with MDD (p < 0.001), moderate and high antidepressant resistance (p < 0.001), obesity (p < 0.001), psychiatric comorbidities (attention-deficit/hyperactivity disorder, substance use disorder, and cluster B and C personality disorder, all p < 0.001), a family history of mental disorders (schizophrenia and mood disorders, all p < 0.05), lower monthly income (p < 0.001), and more mental health visits to the clinic each year (p < 0.001). A composite of demographic characteristics, antidepressant resistance, physical and psychiatric comorbidities, and family history significantly predicted diagnostic conversion from MDD to BD (area under the curve = 0.795, p < 0.001). Compared to adult population, the adolescents and young adults had different factors that were most or less predictive of conversion, which warrants further investigation.

Risk of major mental disorders in the offspring of parents with migraine.

BACKGROUND: Migraine has been associated with mental disorders, however whether parental migraine is associated with an increased risk of major mental disorders (MMDs) in offspring has not been investigated. We aimed to examine the risk of the development of MMDs in the offspring of parents with migraine compared with those of parents without migraine. METHODS: This study used data derived from the Taiwan National Health Insurance Research Database. Offspring of parents with migraine and a control group consisting of offspring of parents without migraine matched for demographic and parental mental disorders were included. Cox regression was used to estimate the risk of MMDs, including schizophrenia, depressive disorder, bipolar disorder, autistic spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Sub-analyses stratified by the fathers and mothers were further performed to separately clarify the risks of MMDs among the offspring. RESULTS: We included 22,747 offspring of parents with migraine and 227,470 offspring of parents without migraine as the controls. Parental migraine was significantly associated with an increased risk of ADHD (reported as hazard ratios with 95% confidence intervals: 1.37, 1.25-1.50), bipolar disorder (1.35, 1.06-1.71), and depressive disorder (1.33, 1.21-1.47) compared to the offspring of parents without migraine. Importantly, sub-analyses showed that only maternal migraine was significantly associated with these risks. CONCLUSIONS: Due to the heavy burden of MMDs, healthcare workers should be aware of the risk of MMDs in the offspring of parents with migraine, particular in mothers.

Risks and familial coaggregation of death by suicide, accidental death and major psychiatric disorders in first-degree relatives of individuals who died by suicide.

BACKGROUND: Evidence suggests a familial coaggregation of major psychiatric disorders, including schizophrenia, bipolar disorder, major depression (MDD), autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). Those disorders are further related to suicide and accidental death. However, whether death by suicide may coaggregate with accidental death and major psychiatric disorders within families remains unclear. AIMS: To clarify the familial coaggregation of deaths by suicide with accidental death and five major psychiatric disorders. METHOD: Using a database linked to the entire Taiwanese population, 68 214 first-degree relatives of individuals who died by suicide between 2003 and 2017 and 272 856 age- and gender-matched controls were assessed for the risks of death by suicide, accidental death and major psychiatric disorders. RESULTS: A Poisson regression model showed that the first-degree relatives of individuals who died by suicide were more likely to die by suicide (relative risk RR = 4.61, 95% CI 4.02-5.29) or accident (RR = 1.62, 95% CI 1.43-1.84) or to be diagnosed with schizophrenia (RR = 1.53, 95% CI 1.40-1.66), bipolar disorder (RR = 1.99, 95% CI 1.83-2.16), MDD (RR = 1.98, 95% CI 1.89-2.08) or ADHD (RR = 1.34, 95% CI 1.24-1.44). CONCLUSIONS: Our findings identified a familial coaggregation of death by suicide with accidental death, schizophrenia, major affective disorders and ADHD. Further studies would be required to elucidate the pathological mechanisms underlying this coaggregation.

Risk of Attempted Suicide Among Patients With IBD: A Nationwide Longitudinal Follow-up Study.

BACKGROUND: Evidence suggests that IBD is related to an increased risk of depressive disorder and suicide. OBJECTIVES: Whether IBD is an independent risk factor for suicide remains unclear. DESIGN: A matched cohort study design. SETTINGS: Taiwan National Health Insurance Research Database. PATIENTS: A total of 3625 adults with IBD aged ≥20 years and 36,250 matched controls were selected between 1997 and 2013 and followed-up to the end of 2013. MAIN OUTCOME MEASURES: Any suicide attempt was identified during the study period. Stratified Cox regression analysis was conducted on each matched pair to investigate the attempted suicide risk between the IBD and control groups. RESULTS: The hazard ratio for any suicide attempt among the patients with IBD was 4.61 (95% CI, 3.29-6.48) compared with controls matched exactly for depressive disorder. No significant difference in suicide attempts was noted between patients with ulcerative colitis (HR, 4.12; 95% CI, 2.69-6.32) and patients with Crohn's disease (HR, 5.78; 95% CI, 3.27-10.22). LIMITATIONS: The incidence of any suicide attempt may be underestimated. CONCLUSION: IBD was an independent risk factor for attempted suicide. However, further studies are required to elucidate the definite pathomechanisms between IBD and suicide. RIESGO DE INTENTO DE SUICIDIO ENTRE PACIENTES CON ENFERMEDAD INFLAMATORIA INTESTINAL UN ESTUDIO DE SEGUIMIENTO LONGITUDINAL A NIVEL NACIONAL: ANTECEDENTES: La evidencia sugiere que la enfermedad inflamatoria intestinal (EII) está relacionada con un mayor riesgo de trastornos depresivos y de suicidios.OBJETIVOS: Sin embargo, aún no está claro si la EII es un factor de riesgo independiente para llegar al suicidio.DISEÑO: Estudio de cohortes de tipo pareado.AJUSTES: Investigación en la base de datos del seguro nacional de salud de Taiwán.PACIENTES: Se seleccionaron un total de 3.625 adultos con EII de ≥20 años y 36.250 controes emparejados entre 1997 y 2013, se les dio un seguimiento hasta finales de 2013.PRINCIPALES MEDIDAS DE RESULTADO: Se identificó cualquier intento de suicidio durante el período del estudio. Se realizó un análisis de regresión de Cox estratificado en cada dupla apareada dentro la investigación del riesgo de intento de suicidio comparado entre los grupos de EII y el grupo control.RESULTADOS: El cociente de riesgo instantáneo (HR) para cualquier intento de suicidio entre los pacientes con EII fue de 4,61 (el intervalo de confianza [IC] del 95 %: 3,29-6,48) en comparación con los controles apareados exactamente en casos de trastorno depresivo. No se observaron diferencias significativas en los intentos de suicidio entre los pacientes con colitis ulcerosa (HR: 4,12, IC 95 %: 2,69-6,32) y enfermedad de Crohn (HR: 5,78, IC 95 %: 3,27-10,22).LIMITACIONES: La incidencia de cualquier intento de suicidio puede estar subestimada.CONCLUSIÓN: La EII fué un factor de riesgo independiente para el intento de suicidio. Sin embargo, se requieren más estudios para dilucidar los mecanismos patogénicos definitivos entre la EII y el suicidio. (Traducción-Dr. Xavier Delgadillo ).

Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients without previous oral anticoagulants or stable under warfarin: a nationwide cohort study.

AIMS: Investigations on non-VKA oral anticoagulants (NOACs) for atrial fibrillation (AF) patients without taking any oral anticoagulants (OACs) or staying well on warfarin were limited. We aimed to investigate the associations between stroke prevention strategies and clinical outcomes among AF patients who were previously well without taking any OACs or stayed well on warfarin for years. METHODS AND RESULTS: The retrospective analysis included a total of 54 803 AF patients who did not experience an ischaemic stroke or intra-cranial haemorrhage (ICH) for years after AF was diagnosed. Among these patients, 32 917 patients who did not receive OACs were defined as the 'original non-OAC cohort' (group 1), and 8007 patients who continuously received warfarin were defined as the 'original warfarin cohort' (group 2). In group 1, compared to non-OAC, warfarin showed no significant difference in ischaemic stroke (aHR 0.979, 95%CI 0.863-1.110, P = 0.137) while those initiated NOACs were associated with lower risk (aHR 0.867, 95%CI 0.786-0.956, P = 0.043). When compared to warfarin, the composite of 'ischaemic stroke or ICH' and 'ischaemic stroke or major bleeding' was significantly lower in the NOAC initiator with an aHR of 0.927 (95%CI 0.865-0.994; P = 0.042) and 0.912 (95%CI 0.837-0.994; P < 0.001), respectively. In group 2, when compared to warfarin, those shifted to NOACs were associated with a lower risk of ischaemic stroke (aHR 0.886, 95%CI 0.790-0.993, P = 0.002) and major bleeding (aHR 0.849, 95%CI 0.756-0.953, P < 0.001). CONCLUSIONS: The NOACs should be considered for AF patients who were previously well without taking OACs and those who were free of ischaemic stroke and ICH under warfarin for years.

Antidepressant drugs use and epilepsy risk: A nationwide nested case-control study.

BACKGROUND: To investigate the association between exposure to antidepressants (ADs) and the risk of epilepsy among patients exposed to ADs. METHOD: We conducted a case-control study using Taiwan's National Health Insurance Research Database between 1998 and 2013. A total of 863 patients with epilepsy and 3,452 controls were included. The dose of ADs was categorized according to the cumulative defined daily dose (cDDD). The risk of epilepsy was assessed using conditional logistic regression analysis. RESULTS: Compared with cDDD < 90, ADs exposure with cDDD > 365 (odds ratio [OR]: 1.37, 95% confidence interval [CI]:1.12-1.68) was associated with an increased risk of epilepsy, but not for those with cDDD 90-365 (OR: 1.07,95% CI: 0.87-1.30) after adjustment for several comorbidities and indications of ADs use. Other identified risk factors include cerebrovascular disease, traumatic brain injury, and central nervous system infection. Subgroup analysis of individual ADs showed that escitalopram (OR: 1.93, 95% CI: 1.12-3.31), venlafaxine (OR: 1.62, 95% CI: 1.13-2.31), mirtazapine (OR: 1.56, 95% CI: 1.00-2.43), paroxetine (OR: 1.44, 95% CI: 1.08-1.94), and fluoxetine (OR: 1.25, 95% CI: 1.01-1.56) had a significantly higher risk of epilepsy. Sertraline, fluvoxamine, citalopram, duloxetine, milnacipran, and bupropion did not show any proconvulsant effects. CONCLUSIONS: The study found an increased risk of epilepsy among patients who were exposed to any ADs, particularly longer-term users. Given the nature of observational studies with residual bias, interpretation should be cautious.

Risk of parental psychiatric disorders among adolescents with major depressive disorder according to response to antidepressant treatment: does the type of antidepressant matter?

BACKGROUND: The genetic load for major depressive disorder (MDD) may be higher in people who develop MDD earlier in life. This study aimed to investigate whether the parents of adolescents with MDD were more likely to have MDD, bipolar disorder (BD), schizophrenic disorder (SZ), alcohol use disorder, or substance use disorder than the parents of adolescents without MDD. We also examined whether the response to antidepressant treatment predicted the likelihood of parental psychiatric disorders. METHODS: In all, 1,758 adolescents aged 12-19 years with antidepressant-resistant depression, 7,032 (1:4) age-/sex-matched adolescents with antidepressant-responsive depression and 7,032 (1:4) age-/sex-matched controls were included. Parental psychiatric disorders of individuals enrolled were assessed. RESULTS: The parents of the adolescents with MDD were more likely to be diagnosed with MDD, BD, SZ, alcohol use disorder, or substance use disorder than the parents of the control group. The parents of adolescents who were antidepressant resistant and the mothers of adolescents who were either treatment resistant or treatment responsive were more likely to be diagnosed with a psychiatric disorder. DISCUSSION: Our study demonstrated that parents of adolescents with MDD may be more likely to be diagnosed with MDD, BD, SZ, alcohol use disorder, or substance use disorder than parents of adolescents without MDD, suggesting the within-disorder transmission and cross-disorder transmission of these psychiatric disorders. Furthermore, the parent's sex and the response to antidepressant treatment may affect the within-disorder transmission of MDD.

Dementia risk in middle-aged patients with schizophrenia, bipolar disorder, and major depressive disorder: a cohort study of 84,824 subjects.

All severe mental disorders, namely schizophrenia, bipolar disorder, and major depression, are associated with dementia. However, a head-to-head comparison study of severe mental disorders and dementia risk is lacking. This study was a retrospective analysis from Taiwan National Health Insurance Database. In the current study, we included 14,137, 14,138, and 14,137 patients aged 45-69 years diagnosed with schizophrenia, bipolar disorder, and major depressive disorder, respectively, between 2001 and 2009 and 42,412 matched controls. Four groups were age-matched based by age of identification. Any dementia, including Alzheimer disease and vascular dementia, was diagnosed from the identification date to the end of 2011. Alzheimer disease was more likely in patients with bipolar disorder (hazard ratio [HR]: 10.37, 95% confidence interval [CI]: 6.93-15.52) and major depression (HR: 8.92, 95% CI: 5.93-13.41) than in those with schizophrenia (HR: 4.50, 95% CI: 2.84-7.13) and in controls. The likelihood of developing vascular dementia during the follow-up period was greater in patients with schizophrenia (HR: 4.55, 95% CI: 3.14-6.59) and bipolar disorder (HR: 4.45, 95% CI: 3.13-6.31) than in those with major depression (HR: 3.18, 95% CI: 2.21-4.58) and in controls. However, the overlapped CIs indicated the non-significant between-category differences. There was an increased risk of Alzheimer disease and vascular dementia in all groups compared with controls. For Alzheimer disease risk was greater bipolar and depression compared with schizophrenia while for vascular dementia risk was greater for bipolar and schizophrenia compared with depression. Our findings may encourage clinicians to closely monitor the trajectory of cognitive function in middle-aged and elderly patients with schizophrenia, bipolar disorder, and major depressive disorder.

Diagnostic progression to schizophrenia in 35,255 patients with obsessive-compulsive disorder: a longitudinal follow-up study.

Evidence suggests a continuity between obsessive-compulsive disorder (OCD) and schizophrenia. However, the factors that may predict diagnostic progression from OCD to schizophrenia remain unclear. A total of 35,255 adolescents and adults with OCD (ICD-9-CM code: 300.3) were enrolled between 2001 and 2010 and followed up at the end of 2011 for the identification of de novo schizophrenia (ICD-9-CM code: 295). The Kaplan-Meier method was used to estimate incidence rates, and the Cox regression was used to determine the significance of candidate predictors. At the end of the 11-year follow-up period, the crude cumulative progression rate from OCD to schizophrenia was 6%, and the estimated progression rate totaled 7.80%. Male sex (hazard ratio: 1.23), obesity (1.77), autism spectrum disorder (1.69), bipolar disorder (1.69), posttraumatic stress disorder (1.65), cluster A personality disorder (2.50), and a family history of schizophrenia (2.57) also were related to an elevated likelihood of subsequent progression to schizophrenia in patients with OCD. Further study is necessary to elucidate the exact pathomechanisms underlying diagnostic progression to schizophrenia in patients with OCD.

Increased Risk of Suicide Attempt in Patients with Alopecia Areata: A Nationwide Population-Based Cohort Study.

BACKGROUND: There is growing evidence that patients with alopecia areata (AA) have an increased risk of developing psychiatric comorbidities. However, the relationship between AA and suicidal behaviors remains unclear. OBJECTIVE: The objective of this study was to investigate the association between AA and suicidal behaviors. METHODS: Participants were recruited from the National Health Insurance Research Database in Taiwan, including 10,515 patients with AA and 10,5150 matched controls, to assess the risk of suicide attempts. A Cox regression model was used for all analyses. RESULTS: Compared with the controls, an increased risk of suicide attempts was observed in patients with AA, with an adjusted hazard ratio of 6.28 (95% confidence interval, 4.47-8.81). Suicide risk remained significantly elevated in AA patients when stratified by underlying psychiatric disorders. The mean age of initial suicidal behaviors was also lower in patients with AA. CONCLUSIONS: Patients with AA had a significantly higher incidence of suicidal attempts than controls, regardless of concurrent psychiatric illness. Further studies are needed to elucidate the pathophysiology of the association between AA and suicidality. In addition, dermatologists should be aware of the increased suicidality of patients with AA.

Inflammatory bowel disease and the associated risk of dry eye and ocular surface injury: a nationwide matched cohort study.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with lacrimal gland dysfunction and ocular inflammation. The objective of this research was to elucidate the temporal relationships between IBD, dry eye disease (DED), and corneal surface damage. METHODS: In a matched nationwide cohort study, we evaluated the risk of DED and corneal surface damage associated with IBD. Multivariable Cox proportional hazards regression analyses were implemented to estimate the risk of ocular complications. RESULTS: A total of 54,293 matched pairs were included for analyses. The median follow-up time was 8.3 years (interquartile range: 5.5 - 10.5). The period incidence of DED was 8.18 and 5.42 per 1000 person-years in the IBD and non-IBD groups, respectively. After adjusting for confounders, statistically significant associations were found between IBD and DED [adjusted hazard ratio (aHR): 1.43, 95% confidence interval (CI): 1.35 - 1.51, p < 0.0001], Sjögren's syndrome-related (aHR: 1.67, 95% CI:1.46 - 1.90, p < 0.0001) and non-Sjögren's syndrome-related subtypes (aHR: 1.38, 95% CI: 1.30 - 1.46, p < 0.0001). Furthermore, increased risks of corneal surface damage (aHR: 1.13, 95% CI: 1.03 - 1.24, p = 0.0094) among the patients with IBD were observed when compared with the controls. Other independent factors associated with corneal surface damage were age (aHR: 1.003), sex (male vs. female, aHR: 0.85), and monthly insurance premium (501-800 vs. 0-500 U.S. dollars, aHR: 1.45; ≥ 801 vs. 0-500 U.S. dollars, aHR: 1.32). CONCLUSIONS: Our results suggested that IBD was an independent risk factor for DED and ocular surface damage. Clinical strategies are needed to prevent visual impairment or losses in these susceptible patients.