Familial Coaggregation of Suicide, Accidental Death, and Major Psychiatric Disorders in First-Degree Relatives of Individuals Dying Accidentally.

OBJECTIVE: To investigate the risks of suicide, accidental death, and major psychiatric disorders in first-degree relatives (FDRs) of people who die accidentally. Evidence has shown that the endophenotypes of impulsivity and risk-taking are known to coaggregate with major psychiatric disorders, suicide, and accidental deaths within families. METHODS: In total, 136,011 FDRs of individuals who died from accidents and 544,044 individuals matched for age and sex who served as a control group were included in the present study. The relative risks of accidental death and suicide were assessed between these groups. Differences in the frequencies of major psychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, and attention deficit hyperactivity disorder (ADHD) between the groups were also identified. RESULTS: The FDRs of individuals who died from accidents were more likely to themselves die from accidents (relative risk [RR] = 4.62) and by suicide (RR = 1.54) compared with individuals in the control group. The FDRs of individuals who died from accidents had an increased risk of developing schizophrenia (RR = 1.24), bipolar disorder (RR = 1.18), major depressive disorder (RR = 1.26), and attention deficit hyperactivity disorder (RR = 1.10) compared with the FDRs of individuals who did not die from accidents. CONCLUSION: Our findings may serve as a reminder to public health officials and clinicians to monitor closely the mental health of the FDRs of individuals who die from accidents.

Obsessive-compulsive disorder and suicide: a longitudinal study in Taiwan.

AIMS: Research evidence has established an association of obsessive-compulsive disorder (OCD) with suicidal thoughts and suicide attempts. However, further investigation is required to determine whether individuals with OCD have higher risk of death by suicide compared with those without OCD. METHODS: Of the entire Taiwanese population, between 2003 and 2017, 56,977 individuals with OCD were identified; they were then matched at a 1:4 ratio with 227,908 non-OCD individuals on the basis of their birth year and sex. Suicide mortality was assessed between 2003 and 2017 for both groups. Time-dependent Cox regression models were used to investigate the difference in suicide risk between individuals with versus without OCD. RESULTS: After adjustment for major psychiatric comorbidities (i.e., schizophrenia, bipolar disorder and major depressive disorder), the OCD group had higher risk of suicide (hazard ratio: 1.97, 95% confidence interval: 1.57-2.48) during the follow-up compared with the comparison group. Furthermore, OCD severity, as indicated by psychiatric hospitalizations due to OCD, was positively correlated with suicide risk. CONCLUSIONS: Regardless of the existence of major psychiatric comorbidities, OCD was found to be an independent risk factor for death by suicide. A suicide prevention program specific to individuals with OCD may be developed in clinical practice in the future.

Familial coaggregation of major psychiatric disorders and neurodevelopmental disorders among first-degree relatives of individuals with generalized anxiety disorder.

BACKGROUND: Anxiety disorders, major psychiatric disorders (e.g., schizophrenia and major affective disorders), and neurodevelopmental disorders (e.g., autism and attention-deficit/hyperactivity disorder [ADHD]) may cluster together within families. However, whether the first-degree relatives (FDRs) of individuals with generalized anxiety disorder (GAD) are at an elevated risk of neurodevelopmental or major psychiatric disorders remains unknown. METHODS: We identified 2,378,190 FDRs of patients with GAD and 9,512,760 birth year-matched and sex-matched controls from Taiwan's National Health Insurance Research Database. Neurodevelopmental disorders, including autism and ADHD, and major psychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, and GAD, were identified. RESULTS: The FDRs-parents, offspring, and siblings-of individuals with GAD were more likely to be diagnosed as having schizophrenia (relative risk: 1.22), bipolar disorder (1.36), major depressive disorder (1.29), autism (1.20), ADHD (1.52), obsessive-compulsive disorder (1.21), and GAD (1.61) than are the FDRs of individuals without GAD. CONCLUSION: Our findings support the notion of a familial coaggregation between GAD, major psychiatric disorders, and neurodevelopmental disorders. Future studies should elucidate the definitive genetic etiology of this familial coaggregation.

Congenital hypothyroidism and risk of subsequent autism spectrum disorder and attention-deficit/hyperactivity disorder in Taiwan.

AIM: Evidence suggests an association between maternal hypothyroidism and risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) in offspring. We examined the risk of ASD and ADHD in individuals with congenital hypothyroidism (CHT). METHODS: A nationwide population-based cohort study enrolled a total of 1260 children younger than 12 years with a confirmed diagnosis of CHT and no prior diagnosis of any neurodevelopmental disorders, selected from the National Health Insurance Research Database of Taiwan between 1998 to 2013. In addition, 12,600 controls matched for sex, age, and residence were selected. Cox proportional hazards analysis was used to investigate the association among CHT, ASD, and ADHD. RESULTS: Children with CHT were associated with a higher incidence of ASD (7.1‰ vs 1.3‰, P < 0.001) and ADHD (39.7‰ vs 18.7‰, P < 0.001) than the control group. Cox regression analyses demonstrated that children with CHT were associated with elevated risks of ASD (hazard ratio [HR], 4.72 [95% confidence interval (CI), 2.08-10.70]) and ADHD (HR, 2.03 [95% CI, 1.49-2.77]), after adjusting for demographic data and family history of major psychiatric disorders, compared with the control group. CONCLUSION: Children with CHT were associated with approximately a two-fold increased risk of ADHD and a four-fold increased risk of ASD than the control group. Our study highlights the need for future research to elucidate the potential pathophysiology among CHD, ASD, and ADHD.

Risk of Periodontitis in Adolescents With Attention Deficit Hyperactivity Disorder: A Cohort Study of 81,055 Participants.

OBJECTIVES: Previous studies have demonstrated poor oral hygiene in children with attention deficit hyperactivity disorder (ADHD). However, the association between ADHD and periodontitis is still unclear. METHODS: In all, 16,211 adolescents with ADHD and 162,110 age- and sex-matched controls participated in the study between 2001 and 2011. To identify the occurrence of periodontitis, the participants were followed up till the end of 2011. Confounding factors, including smoking, diabetes, and depressive disorder, were assessed and adjusted in the Cox regression models. RESULTS: Adolescents with ADHD (HR: 2.29) were more likely to develop periodontitis later in life than controls. We additionally observed the beneficial effect of atomoxetine (HR: 0.42) on the periodontitis risk among adolescents with ADHD. However, this finding should be interpreted cautiously given the small sample (n = 290) of children taking atomoxetine in the present study. CONCLUSIONS: ADHD is an independent risk factor for subsequent periodontitis development. Oral health should be closely monitored in adolescents with ADHD. Future investigation of the shared pathomechanisms between periodontitis and ADHD is warranted.

Risk of Dementia in Different Types of Cancer Survivors: A Nationwide Cohort Study.

OBJECTIVES: The association between specific types of malignancies and the subsequent risk of dementia remains unknown. DESIGN: A retrospective population-based cohort study based on data from Taiwan National Health Insurance Research Database. SETTING AND PARTICIPANTS: We recruited 32,250 patients who survived malignancies and 322,500 controls between 1998 and 2011 and followed them up until the end of 2013. MEASUREMENTS: Diagnoses of dementia (including Alzheimer's disease (AD), vascular dementia (VaD), and unspecified dementia) was made during the follow-up period. Cox regression analyses were performed after adjusting for potential confounders. A sensitivity analysis was conducted to exclude patients with prodromal dementia. RESULTS: Cancer survivors were more likely to develop AD (hazard ratio [HR]: 1.68, 95% confidence interval [CI]: 1.38-2.06), unspecified dementia (HR: 1.19, 95% CI: 1.07-1.32), and any dementia (HR: 1.26, 95% CI: 1.16-1.37) compared with controls after adjusting for potential confounders. Importantly, cancers of the digestive and genitourinary organs seem to be associated with AD, unspecified dementia, and any dementia, whereas only malignant neoplasms of the brain are more likely to develop into VaD. Sensitivity analyses after exclusion of the first three or five years of observation and after exclusion of case enrollment before 2009 or 2007 showed consistent findings. CONCLUSION: Cancer survivors are at higher risk of subsequent dementia. Different types of cancer survivors may contribute to variable risks of specific dementias. Further studies are necessary to investigate the underlying mechanisms in cancer survivors and patients with dementia.

Risks of developing major psychiatric disorders among child and adolescent intensive care unit survivors.

BACKGROUND: The mental health of child and adolescent intensive care unit (ICU) survivors is increasingly being researched. However, the literature on how various types of critical illness influence specific psychiatric disorders remains limited. METHODS: This study analyzed the data of 8704 child and adolescent ICU survivors and 87,040 age-, sex-, family income-, and residence-matched controls who were followed from enrollment to the end of 2013; the data covered the period from 1996 to 2013 and were extracted from a nationwide data set. The primary outcomes were the risks of five major psychiatric disorders (MPDs), namely schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), obsessive compulsive disorder (OCD), and posttraumatic stress disorder (PTSD). RESULTS: Relative to the controls, the child and adolescent ICU survivors (mean age = 10.33 years) exhibited higher risks of developing five MPDs. The associated hazard ratios (HRs) and confidence intervals (CIs) are as follows: PTSD, HR = 4.67, 95 % CI = 2.42-9.01; schizophrenia, HR = 3.19, 95 % CI = 2.27-4.47; BD, HR = 2.02, 95 % CI = 1.33-3.05; OCD, HR = 1.96, 95 % CI = 1.21-3.16; and MDD, HR = 1.68, 95 % CI = 1.44-1.95. The risks of developing MPDs varied across multiple types of critical illness related to ICU admission. CONCLUSIONS: The risks of MPDs were significantly higher among the child and adolescent ICU survivors than among the controls. The development of appropriate MPD prevention strategies should be emphasized for this vulnerable population.

Thalamocortical functional connectivity and rapid antidepressant and antisuicidal effects of low-dose ketamine infusion among patients with treatment-resistant depression.

Previous studies have shown an association between the thalamocortical dysconnectivity and treatment-resistant depression (TRD). Whether a single subanesthetic dose of ketamine may change thalamocortical connectivity among patients with TRD is unclear. Whether these changes in thalamocortical connectivity is associated with the antidepressant and antisuicidal effects of ketamine treatment is also unclear. Two resting-state functional MRIs were collected in two clinical trials of 48 patients with TRD (clinical trial 1; 32 receiving ketamine, 16 receiving a normal saline placebo) and 48 patients with TRD and strong suicidal ideation (clinical trial 2; 24 receiving ketamine, 24 receiving midazolam), respectively. All participants underwent rs-fMRI before and 3 days after infusion. Seed-based functional connectivity (FC) was analyzed in the left/right thalamus. FCs between the bilateral thalamus and right middle frontal cortex (BA46) and between the left thalamus and left anterior paracingulate gyrus (BA8) increased among patients in the ketamine group in clinical trials 1 and 2, respectively. FCs between the right thalamus and bilateral frontal pole (BA9) and between the right thalamus and left rostral paracingulate gyrus (BA10) decreased among patients in the ketamine group in clinical trials 1 and 2, respectively. However, the associations between those FC changes and clinical symptom changes did not survive statistical significance after multiple comparison corrections. Whether ketamine-related changes in thalamocortical connectivity may be associated with ketamine's antidepressant and antisuicidal effects would need further investigation. Clinical trials registration: UMIN Clinical Trials Registry (UMIN-CTR): Registration number: UMIN000016985 and UMIN000033916.

Effects of Low-Dose Ketamine Infusion on the Positive and Negative Domains of Hopelessness and Suicidal Thoughts.

Background: Low-dose ketamine infusion has been demonstrated to exert antisuicidal effects on patients with treatment-resistant depression (TRD) and strong suicidal ideation. Although evidence suggests an association between hopelessness and suicidality, very few studies have investigated the antihopelessness effects of ketamine.Methods: This study included 84 patients with TRD and strong suicidal ideation. The diagnosis of depression was based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnostic criteria for major depressive disorder. They were randomly assigned to receive a single infusion of either 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. Hopelessness and suicidal symptoms were assessed at baseline, at 240 minutes postinfusion, and on Days 2, 3, 7, and 14 postinfusion. The assessments were performed using the self-report Beck Hopelessness Scale (BHS) and Positive and Negative Suicide Ideation Inventory (PANSI). The analysis focused on the positive and negative domains of the BHS and PANSI, respectively. The clinical trial was conducted between August 15, 2018, and November 30, 2021.Results: Statistical analyses performed using a generalized linear model revealed that the ketamine group had significantly higher PANSI-positive (P = .008) and lower PANSI-negative (P = .015) suicidal ideation scores on Day 2 postinfusion than did the midazolam group. At 240 minutes postinfusion, the ketamine group had significantly lower BHS-negative domain scores than did the midazolam group (P = .031). Notably, the observed ketamine-induced reduction in hopelessness at 240 minutes postinfusion was associated with its antisuicidal effect on Day 2 postinfusion.Discussion: A single infusion of low-dose ketamine resulted in a brief (∼4 hours) yet significant reduction in hopelessness. Subjective antisuicidal effects of ketamine were noted on Day 2 postinfusion. Further studies are needed to elucidate the neuromechanisms underlying the antihopelessness and antisuicidal effects of ketamine.Trial Registration: UMIN Clinical Trials Registry identifiers: UMIN000033916 and UMIN000033760.

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.

Poor subjective sleep quality and trait impulsivity in patients with bipolar disorder.

BACKGROUND: Sleep disturbance and impulsivity are key components of mood vulnerability in bipolar disorder (BD), but few studies have assessed the association between these two symptoms among patients with BD. METHODS: Forty-seven euthymic patients with bipolar I disorder (BDI) or bipolar II disorder (BDII) and 58 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Trait impulsivity was measured using the Barratt Impulsiveness Scale Version 11 (BIS-11), which yielded 3 second-order factors: attention, motor, and non-planning. Subjective sleep quality was assessed using the self-reported Pittsburgh Sleep Quality Index (PSQI). General linear models (GLMs) were used to assess the associations between subjective poor sleep and trait impulsivity with multiple testing corrections. RESULTS: Patients with BD scored higher in BIS-11 and PSQI than healthy controls. PSQI total scores positively correlated with BIS-11 total scores, while sleep disturbance and daytime dysfunction were associated with attentional impulsiveness after controlling for covariates. Participants with higher PSQI total scores (>10) had higher scores in BIS-11 total, attention, and non-planning than those with low PSQI scores (≤5). CONCLUSION: These findings support the hypothesis that poor sleep quality might lead to impulsivity and add to the growing evidence that improving sleep quality may be a therapeutic target for patients with BD.

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.

Association between cortical thickness or surface area and divergent thinking in patients with bipolar disorder.

OBJECTIVE: Divergent thinking is a critical creative cognitive process. Its neural mechanisms have been well-studied through structural and functional imaging in healthy individuals but are less explored in patients with bipolar disorder (BD). Because of the traditional link between creativity and BD, this study investigated the structural correlates of divergent thinking in patients with BD through surface-based morphometry. METHODS: Fifty-nine patients diagnosed with BD I or BD II (35.3 ± 8.5 years) and 56 age- and sex-matched controls (33.9 ± 7.4 years) were recruited. The participants underwent structural magnetic resonance imaging and an evaluation of divergent thinking by using the Chinese version of the Abbreviated Torrance Test for Adults (ATTA). FreeSurfer 7.0 was used to generate thickness and surface area maps for each participant. Brainwise regression of the association between cortical thickness or surface area and ATTA performance was conducted using general linear models. RESULTS: Divergent thinking performance did not differ significantly between the patients with BD and the healthy controls. In these patients, total ATTA score was negatively correlated with cortical thickness in the right middle frontal gyrus, right occipital, and left precuneus but positively correlated with the surface area of the right superior frontal gyrus. By contrast, total ATTA scores and cortical thickness or surface area were not significantly correlated among the controls. CONCLUSION: The findings indicate that divergent thinking involves cerebral structures for executive control, mental imagery, and visual processing in patients with BD, and the right prefrontal cortex might be the most crucial of these structures.

Susceptibility to Treatment-Resistant Depression Within Families.

Importance: Antidepressant responses and the phenotype of treatment-resistant depression (TRD) are believed to have a genetic basis. Genetic susceptibility between the TRD phenotype and other psychiatric disorders has also been established in previous genetic studies, but population-based cohort studies have not yet provided evidence to support these outcomes. Objective: To estimate the TRD susceptibility and the susceptibility between TRD and other psychiatric disorders within families in a nationwide insurance cohort with extremely high coverage and comprehensive health care data. Design, Setting, and Participants: This cohort study assessed data from the Taiwan national health insurance database across entire population (N = 26 554 001) between January 2003 and December 2017. Data analysis was performed from August 2021 to April 2023. TRD was defined as having experienced at least 3 distinct antidepressant treatments in the current episode, each with adequate dose and duration, based on the prescribing records. Then, we identified the first-degree relatives of individuals with TRD (n = 34 467). A 1:4 comparison group (n = 137 868) of first-degree relatives of individuals without TRD was arranged for the comparison group, matched by birth year, sex, and kinship. Main Outcomes and Measures: Modified Poisson regression analyses were performed and adjusted relative risks (aRRs) and 95% CIs were calculated for the risk of TRD, the risk of other major psychiatric disorders, and different causes of mortality. Results: This study included 172 335 participants (88 330 male and 84 005 female; mean [SD] age at beginning of follow-up, 22.9 [18.1] years). First-degree relatives of individuals with TRD had lower incomes, more physical comorbidities, higher suicide mortality, and increased risk of developing TRD (aRR, 9.16; 95% CI, 7.21-11.63) and higher risk of other psychiatric disorders than matched control individuals, including schizophrenia (aRR, 2.36; 95% CI, 2.10-2.65), bipolar disorder (aRR, 3.74; 95% CI, 3.39-4.13), major depressive disorder (aRR, 3.65; 95% CI, 3.44-3.87), attention-deficit/hyperactivity disorders (aRR, 2.38; 95% CI, 2.20-2.58), autism spectrum disorder (aRR, 2.26; 95% CI, 1.86-2.74), anxiety disorder (aRR, 2.71; 95% CI, 2.59-2.84), and obsessive-compulsive disorder (aRR, 3.14; 95% CI, 2.70-3.66). Sensitivity and subgroup analyses validated the robustness of the findings. Conclusions and Relevance: To our knowledge, this study is the largest and perhaps first nationwide cohort study to demonstrate TRD phenotype transmission across families and coaggregation with other major psychiatric disorders. Patients with a family history of TRD had an increased risk of suicide mortality and tendency toward antidepressant resistance; therefore, more intensive treatments for depressive symptoms might be considered earlier, rather than antidepressant monotherapy.

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.

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.

Congenital cleft lip and palate and elevated risks of major psychiatric disorders: A nationwide longitudinal study.

BACKGROUND: Congenital cleft lip and palate (CCLP) may be associated with major psychiatric disorders, including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia, bipolar disorder, and major depressive disorder. METHODS: From the Taiwan National Health Insurance Research Database, 1,158 children and adolescents with CCLP and 11,580 age/sex-matched controls without CCLP were included in this study between 2001 and 2010; they were followed up until the end of 2011 to identify the aforementioned major psychiatric disorders. RESULTS: After adjustment for age, sex, income, residence, and family history, the Cox regression model revealed a positive relationship of CCLP with subsequent schizophrenia (hazard ratio [HR]: 7.60, 95% confidence interval [CI]: 2.03-28.54), ASD (HR: 6.03, 95% CI: 1.76-20.61), and ADHD (HR: 7.33, 95% CI: 5.01-10.73). DISCUSSION: These findings suggest that clinicians should be attentive to the presence or emergence of mental health conditions in patients with CCLP. Further studies are necessary to investigate the pathogenesis between CCLP and major psychiatric disorders.

Cause-specific mortality and comorbid neurodevelopmental disorder in 167,515 patients with bipolar disorder: An entire population longitudinal study.

OBJECTIVE: Studies addressing premature mortality in bipolar disorder (BD) patients are limited by small sample sizes. Herein, we used almost 99 % of the population of Taiwan to address this issue, and its association with comorbid neurodevelopmental disorders and severe BD. METHODS: Between 2003 and 2017, we enrolled 167,515 individuals with BD and controls matched 1:4 for sex and birth year from the National Health Insurance Database linked to the Database of National Death Registry in Taiwan. Time-dependent Cox regression models were used to examine cause-specific mortality (all-cause, natural, and unnatural causes [accidents or suicide]). RESULTS: With adjustments of sex, age, income, urbanization, and physical conditions, suicide was associated with the highest risk of mortality (reported as hazard ratio with 95 % confidence interval: 9.15; 8.53-9.81) among BD patients, followed by unnatural (4.94; 4.72-5.17), accidental (2.15; 1.99-2.32), and natural causes (1.02; 1.00-1.05). Comorbid attention-deficiency hyperactivity disorder did not contribute to the increased risk of cause-specific mortality; however, comorbid autism spectrum disorder (ASD) increased such risks, particularly for natural (3.00; 1.85-4.88) and accidental causes (7.47; 1.80-31.1). Cause-specific mortality revealed a linear trend with the frequency of psychiatric hospitalization (all, p for trend <0.001), and BD patients hospitalized twice or more each year had 34.63-fold increased risk of suicide mortality (26.03-46.07). CONCLUSIONS: BD patients with a higher frequency of psychiatric hospitalization have the highest risk of suicide mortality, and comorbid ASD was associated with an increased risk of natural and accidental causes of mortality.

Appetite hormone dysregulation and executive dysfunction among adolescents with bipolar disorder and disruptive mood dysregulation disorder.

Appetite hormone dysregulation may play a role in the pathomechanisms of bipolar disorder and chronic irritability. However, its association with executive dysfunction in adolescents with bipolar disorder and those with disruptive mood dysregulation disorder (DMDD) remains unclear. We included 20 adolescents with bipolar disorder, 20 adolescents with DMDD, and 47 healthy controls. Fasting serum levels of appetite hormones, including leptin, ghrelin, insulin, and adiponectin were examined. All participants completed the Wisconsin Card Sorting Test. Generalized linear models with adjustments for age, sex, body mass index, and clinical symptoms revealed that patients with DMDD had elevated fasting log-transformed insulin levels (p = .023) compared to the control group. Adolescents with DMDD performed worse in terms of the number of tries required to complete tasks associated with the first category (p = .035), and adolescents with bipolar disorder performed worse in terms of the number of categories completed (p = .035). A positive correlation was observed between log-transformed insulin levels and the number of tries required for the first category (ß = 1.847, p = .032). Adolescents with DMDD, but not those with bipolar disorder, were more likely to exhibit appetite hormone dysregulation compared to healthy controls. Increased insulin levels were also related to executive dysfunction in these patients. Prospective studies should elucidate the temporal association between appetite hormone dysregulation, executive dysfunction, and emotional dysregulation.