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.

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.

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.

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.

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.

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.

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.

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.

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.

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.