The Association between Autism Spectrum Disorder and Precocious Puberty: Considering Effect Modification by Sex and Neuropsychiatric Comorbidities.

Limited knowledge is available about the association between autistic spectrum disorder (ASD) and precocious puberty. Our study examined the association between the two medical conditions and effect modification by sex and neuropsychiatric comorbidities in a nationwide population. To compare the risk of precocious puberty between ASD and non-ASD cases, we conducted a Cox regression analysis using ASD as the exposure and time to precocious puberty as the outcome. We adjusted for sex, attention-deficit/hyperactivity disorder (ADHD), tic disorder, obsessive-compulsive disorder (OCD), anxiety disorder, intellectual disability, and epilepsy. We performed a moderation analysis to examine the potential moderating effects of sex and comorbidities. Patients with ASD were prone to have precocious puberty, with an adjusted hazard ratio (aHR) of 1.80 (95% CI: 1.61-2.01). For effect modification, sex, specifically females, moderated the association between ASD and precocious puberty, with a relative excess risk due to interaction (RERI) of 7.35 (95% CI 4.90-9.80). No significant effect modification was found for any of the comorbidities within the scope of additive effect modification. We found that patients with ASD were prone to precocious puberty, regardless of sex or comorbid neuropsychiatric disorders. Girls with ASD are at a particularly higher risk of developing precocious puberty.

The relationship between schizophrenia or schizoaffective disorder and type 1 diabetes mellitus: a scoping review of observational studies.

OBJECTIVE: Both schizophrenia and type 1 diabetes mellitus (T1D) are known as immune-related disorders. We systematically reviewed observational studies to explore the relationship between schizophrenia or schizoaffective disorder and T1D. METHODS: A preliminary search of articles was completed using the following databases: Airiti Library, CINAHL Complete (via EBSCOhost), OVID MEDLINE, Embase, and PubMed. Two researchers independently assessed each study's quality based on Joanna Briggs Institute (JBI). A narrative review summarized the potential relationship between the two diseases. RESULTS: Eleven studies were included in the final analysis. Six observational studies investigated the risk of schizophrenia and schizoaffective disorder in patients with T1D. Two studies showed negative correlations, one showed no correlation, and three showed positive correlations. On the other hand, five studies reported the prevalence of T1D in patients with schizophrenia. Two of them showed positive associations, and three others showed no association. Although the majority of the included studies suggested a positive association between the two medical conditions, these studies were still too heterogeneous to draw consistent results. CONCLUSION: We found conflicting results regarding the bidirectional relationship between schizophrenia or schizoaffective disorder and T1D. These may stem from differences in study design, sampling methods, or definition of diagnoses, which are essential aspects to consider in future research.

Association Between Maternal Mood Disorders and Schizophrenia and the Risk of Type 1 Diabetes in Offspring: A Nationwide Cohort Study.

Objective: Our study aimed to determine whether mothers with bipolar disorder, major depressive disorder, schizophrenia, or schizoaffective disorder affected the risk of type 1 diabetes (T1D) in their offspring. Methods: We conducted a nationwide cohort study by using data from Taiwan's National Health Insurance Research Database and the Maternal and Child Health Database from 2004 to 2018. A total of 2,556,640 mother-child pairs were identified. Cox proportional hazards models were used to compare the risk of T1D between children born to mothers with mood disorders and schizophrenia and those without. Results: No significant difference in risk of T1D was observed between the offspring of mothers with major psychiatric disorders and those without (adjusted hazard ratio (aHR) of 0.86 with a 95% confidence interval (CI) of 0.58-1.24). In subgroup analysis, we found an aHR of 1.81 with a 95% CI of 0.83-3.82 in the maternal bipolar disorder on the risk of T1D in offspring and an aHR of 0.87 (95% CI: 0.59-1.25) in maternal major depressive disorder. In the schizophrenia/schizoaffective disorder group, aHR cannot be obtained due to lesser than three events in the analysis. Conclusion: The risk of T1D in offspring of mothers with mood disorders and schizophrenia was not significant. However, children born to mothers with bipolar disorder may have a tendency to develop T1D. The relationship between maternal psychiatric disorders and the risk of T1D in offspring warrants further investigation in studies with longer follow-up periods.

Depression, Diabetes Mellitus and Mortality in Older Adults: A National Cohort Study in Taiwan.

Purpose: Diabetes mellitus (DM) increases the risk of cardiovascular and all-cause mortality. The coexistence of depression and DM is associated with an increased risk of DM complications and functional morbidity. The independent effect of depression on mortality in patients with DM is unclear, and relevant Asian studies have provided inconsistent results. Accordingly, this study assessed the independent and additive effects of DM and depression on mortality in a nationally representative cohort of older adults in Taiwan over a 10-year observation period. Patients and Methods: A total of 5041 participants aged 50 years or older were observed between 1996 and 2007. We defined depression as a score of ≥8 on the 10-item Center for Epidemiologic Studies Depression (CES-D 10) scale. Additionally, we defined participants as having type 2 DM if they had received a diagnosis of type 2 DM from a health-care provider. Cox proportional hazard models were applied to analyze predictors of mortality in depression and DM comorbidity groups. Results: During the 10-year follow-up period, 1637 deaths were documented. After adjustment for potential confounders, the hazard ratios for mortality in participants with both depression and DM, DM only, and depression only were 2.47 (95% confidence interval [CI]: 2.02-3.03), 1.95 (95% CI: 1.63-2.32), and 1.23 (95% CI: 1.09-1.39), respectively. Conclusion: The co-occurrence of depression with DM in Asian adults increased overall mortality rates. Our results indicate that the increased mortality hazard in individuals with DM and depression was independent of sex.

Association of Prenatal Maternal Anemia with Tics and Tourette's Syndrome in Offspring.

Iron deficiency anemia (IDA) accounts for most of the anemia in pregnancy, and iron is essential for neurodevelopment. Tics and Tourette's syndrome (TS) are neurodevelopmental disorders that manifest in childhood. A few studies reported an inconclusive association between iron deficiency and tics in children. No study has investigated the relationship between prenatal maternal anemia and tics in children. We aimed to assess the relationship between prenatal anemia exposure and the incidence of tics or TS in offspring. We linked the Taiwan National Health Insurance Research Database to the Maternal and Child Health Database for the analysis and identified 153,854 children with prenatal anemia exposure and 2,014,619 children without prenatal anemia exposure from 2004 to 2016 and followed them through 2017. Cox regression models were applied to compare the risk of tics or TS between the exposed and nonexposed groups. Among the exposed group, 37,832 were exposed at ≤12 weeks of gestational age (GA) and 116,022 at >12 weeks of GA. We observed an increased risk of tics and TS in those exposed at ≤12 weeks compared with the nonexposed group (adjusted hazard ratio (aHR) = 1.23, 95% confidence interval (CI): 1.12-1.34). The result remained consistent after adjusting for birth year, sex, birth order, maternal age, low-income levels, gestational age, birth weight, and alcohol use and smoking during pregnancy (aHR = 1.16, CI: 1.04-1.28). Fetuses exposed to maternal anemia at ≤12 weeks of GA are at high risk of tics or TS. However, this effect was attenuated to insignificance in the sibling comparison. Our study highlights the importance of detection of anemia during pregnancy and proper timing of iron supplementation.

Evidence-Based Expert Consensus Regarding Long-Acting Injectable Antipsychotics for Schizophrenia from the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN).

OBJECTIVE: Schizophrenia is a chronic, debilitating psychiatric disorder with a high risk of relapse. Nonadherence to medication is a significant contributor to poor outcomes. Although long-acting injectable (LAI) antipsychotics prevent the relapse of schizophrenia, several factors present obstacles to the use of LAI antipsychotics, and clinical guidelines for LAI antipsychotics remain limited. To provide clinical recommendations, the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN) developed consensus statements for the effectiveness, target populations, initiation timing, and particular clinical situations for the use of LAI antipsychotics in patients with schizophrenia. METHODS: After a systematic literature review, a working group drafted consensus statements for the selected clinical topics and determined the levels of evidence-based recommendation based on the latest World Federation of Societies of Biological Psychiatry grading system. A scientific committee evaluated the draft statements and decided the final recommendations regarding the grades by anonymous voting after incorporating clinical experience and practice into the evidence from research. RESULTS: The TSBPN proposed ten consensus statements for the application of LAI antipsychotics. The current evidence supported that LAI antipsychotics could be a treatment option for all schizophrenia patients, including first-episode patients. LAI antipsychotics could be initiated both during an acute psychotic episode and when patients are stable. The consensus also gave recommendations for particular clinical situations with insufficient scientific data, such as for use in elderly or adolescent patients, patients with treatment-resistant schizophrenia, and breakthrough psychosis, and strategies to assist patients/caregivers with decision making. CONCLUSIONS: The consensus statements developed by the TSBPN provide evidence-based clinical recommendations and could give clinicians more confidence when prescribing LAI antipsychotics to treat schizophrenia, thereby improving treatment outcomes.

Effect of medication on risk of traumatic brain injury in patients with bipolar disorder: A nationwide population-based cohort study.

BACKGROUND: Increased traumatic brain injury (TBI) risk was found in patients with bipolar disorder (BPD). Whether the medications for BPD and dosage moderate the risk of TBI is not clear. AIM: This study aimed to determine whether an association exists between BPD and TBI and whether the prescription of psychotropics moderates TBI risk. METHODS: A total of 5606 individuals who had received diagnoses of BPD between January 1, 1997 and December 31, 2013 and 56,060 matched controls without BPD were identified from Taiwan's National Health Insurance Research Database. Cases and controls were followed until the date of TBI diagnosis. RESULTS: BPD was associated with a high risk of TBI (adjusted hazard ratio (aHR): 1.85; 95% CI: 1.62-2.11). Patients with BPD, with or without a history of psychiatric hospitalization, had increased risks of TBI (aHR: 1.94, 95% CI: 1.57-2.4 and aHR: 1.82, 95% CI: 1.55-2.1, respectively). The prescription of typical antipsychotics (0 < defined daily dose (DDD) < 28: hazard ratio (HR) = 1.52, 95% CI: 1.19-1.94; ⩾28 DDD: HR = 1.54, 95% CI: 1.15-2.06) and tricyclic antidepressants (TCAs) (0 < DDD < 28: HR = 1.73, 95% CI: 1.26-2.39; ⩾28 DDD: HR = 1.52, 95% CI: 1.02-2.25) was associated with higher TBI risk. Patients receiving higher doses of benzodiazepines (BZDs) (cumulative dose ⩾28 DDD) had a higher TBI risk (HR = 1.53, 95% CI: 1.13-2.06). CONCLUSION: Patients with BPD have a higher risk of TBI. The use of typical antipsychotics, TCAs, or high-dose BZDs increases the risk of TBI in BPD.

New Use for Old Drugs: The Protective Effect of Risperidone on Colorectal Cancer.

Background: The potential of old drugs in novel indications is being greatly valued. We propose a triple-model study involving population-based, cell, and animal studies to investigate the effects of risperidone, a type of second-generation antipsychotic (SGA) drug, on colorectal cancer. Methods: We used data from Taiwan's National Health Insurance Research Database between 1997 and 2013 to compare 101,989 patients with colorectal cancer and 101,989 controls. Conditional logistic regression analyses were used to explore the association between SGA exposure and the risk of colorectal cancer. The following bench studies were performed to evaluate the findings of the population-based study. Results: We found that SGAs had been less commonly used in colorectal cancer patients than in controls. The colorectal cancer risk was reduced with an increase in the cumulative defined daily dose (cDDD) of SGAs. The adjusted odds ratio of antipsychotic use for cDDD days was 0.32 (95% CI: 0.25-0.42). Risperidone exhibited the most prominent tumor inhibition effect in a cell screen study. Bench data revealed that risperidone significantly induced apoptosis and elevated intracellular ROS in human SW480 cells and suppressed the proliferation of the xenografted SW480 tumor in nude mice. Conclusion: This triple-model study demonstrates the association between risperidone usage and a lower risk of colorectal cancer.

Dosage of methylphenidate and traumatic brain injury in ADHD: a population-based study in Taiwan.

Preventive effect of stimulants on the risk of brain injuries had been reported. The aim of this study is to determine the extent to which methylphenidate (MPH) prescription moderates the risk of traumatic brain injuries (TBI) in individuals with attention-deficit/hyperactivity disorder (ADHD). Individuals with a recent diagnosis of ADHD between January 1997 and December 2013 (n = 163,618) were identified from Taiwan's National Health Insurance Research Database. A total of 124,438 adolescents and children with ADHD and without prior TBI diagnoses were included and evaluated for subsequent TBI. Methylphenidate prescription duration was subgrouped by the annual average cumulative defined daily dose (DDD): 0, >0 to ≤28, > 28 to ≤84, and >84. We identified 11,463 diagnoses of TBI among 124,438 adolescents and children with ADHD. A Cox regression model was used to investigate whether MPH prescription influenced the risk for TBI after adjusting for sex, age, level of urbanization, seizure, autism and sedative-anxiolytics use. A reduced TBI incidence was observed with MPH prescription DDDs > 84. The protective effect of MPH against TBI persisted after adjusting for confounding factors [hazard ratio (HR) = 0.49; 95% confidence interval (CI): 0.47-0.51]. There was also statistically significant difference in risk for TBI in subjects receiving > 0 to ≤28 or >28 to ≤84 DDDs of MPH treatment (HR = 0.88, 95% CI = 0.83-0.92; HR = 0.76, 95% CI = 0.72-0.80, respectively) when compared with subjects not receiving treatment with MPH. Treatment with MPH for greater than 84 DDDs reduced the risk for TBI among children with ADHD.

Correlation between brain circuit segregation and obesity.

Obesity is a major public health problem. Herein, we aim to identify the correlation between brain circuit segregation and obesity using multimodal functional magnetic resonance imaging (fMRI) techniques and analysis. Twenty obese patients (BMI=37.66±5.07) and 30 healthy controls (BMI=22.64±3.45) were compared using neuroimaging and assessed for symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS). All participants underwent resting-state fMRI (rs-fMRI) and T1-weighted imaging using a 1.5T MRI. Multimodal MRI techniques and analyses were used to assess obese patients, including the functional connectivity (FC), amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), graph theoretical analysis (GTA), and voxel-based morphometry (VBM). Correlations between brain circuit segregation and obesity were also calculated. In the VBM, obese patients showed altered gray matter volumes in the amygdala, thalamus and putamen. In the FC, the obesity group showed increased functional connectivity in the bilateral anterior cingulate cortex and decreased functional connectivity in the frontal gyrus of default mode network. The obesity group also exhibited altered ALFF and ReHo in the prefrontal cortex and precuneus. In the GTA, the obese patients showed a significant decrease in local segregation and a significant increase in global integration, suggesting a shift toward randomization in their functional networks. Our results may provide additional evidence for potential structural and functional imaging markers for clinical diagnosis and future research, and they may improve our understanding of the underlying pathophysiology of obesity.

Suicide risk reduction in youths with attention-deficit/hyperactivity disorder prescribed methylphenidate: A Taiwan nationwide population-based cohort study.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) youths have increased suicide risk. Nevertheless, the beneficial effects of methylphenidate (MPH) on suicide attempt have received relatively little attention. AIMS: To investigate the MPH usage and the risk of suicide attempt among ADHD youths. METHODS: We identified 84,898 youths less than 18 years old with ADHD diagnosis between 1997 and 2013 from National Health Insurance, and examined whether MPH use affected suicide attempt risk using Cox proportional-hazards models. OUTCOME AND RESULTS: Among ADHD youths, reduction of suicide risk was found in patients prescribed 90-180days of MPH after adjusting for confounding factors (hazard ratio (HR): 0.41, 95% confidence interval (CI): 0.19-0.90) and a greater reduction in those prescribed more than 180days of MPH (HR: 0.28, 95% CI: 0.17-0.48). CONCLUSIONS AND IMPLICATIONS: We observed a 59% suicide attempt risk reduction among ADHD youths prescribed between 90 and 180days and a 72% risk reduction in those prescribed more than 180days of MPH. The protective benefit observed by the group prescribed MPH for longer duration underscores the importance of psychoeducation and compliance enhancement as part of ADHD management. Indication bias is identified as a limitation of this study, and future self-case control study to investigate the association between suicide attempt and ADHD medication is suggested. WHAT THIS PAPER ADDS: This nationwide population-based cohort study showed that among ADHD youths, reduction of suicide risk was observed in patients prescribed MPH for duration 90days and longer, underscoring the importance of appropriate ADHD pharmacotherapy and enhancing drug compliance.

Correction: The association between methylphenidate treatment and the risk for fracture among young ADHD patients: A nationwide population-based study in Taiwan.

[This corrects the article DOI: 10.1371/journal.pone.0173762.].

The association between methylphenidate treatment and the risk for fracture among young ADHD patients: A nationwide population-based study in Taiwan.

Attention-deficit hyperactivity disorder (ADHD) is associated with higher risk for fracture. Whether the medical treatment for ADHD would mitigate the risk remains unclear. In this study, we sought to investigate the effect of methylphenidate treatment on risk for fracture, as well the moderational role of treatment duration on the risk of fracture, in a large national sample. Cases less than 18 years old were identified from Taiwan's National Health Insurance Research Database with a new primary diagnosis of ADHD (ICD-9:314) between 1996 and 2013. A total of 6201 cases with ADHD were included as the study cohort. The cases were divided into 3 groups according to the duration of methylphenidate treatment (0, 1-180, and more than 180 days). All groups were followed until the end of 2013 for first diagnoses of fracture (ICD-9 codes 800 to 829). Cox proportional hazards models were applied. Compared to the group without methylphenidate treatment, the risk for fracture was lower among the group treated for more than 180 days. The adjusted hazard ratio was 0.77 (95% Confidence interval: 0.63-0.94). The groups treated for 180 days or fewer had no significant difference in the risk for fracture. In conclusion, methylphenidate treatment was associated with lower risk for fracture among ADHD patients. The association was evident only in the cohort treated for more than 180 days.

Association between depression and enterovirus infection: A nationwide population-based cohort study.

Enterovirus (EV) infection is common among children and adolescents. Few studies have investigated the relationship of depression after EV infection. This study explores an association between EV infection and subsequent depression in children and adolescents and assesses the risk of depression after EV infection with central nervous system involvement in a nationwide population-based retrospective cohort.A random sample of 1,000,000 people was derived from Taiwan National Health Insurance Research Database and we identified enrollees less than 18 years with EV infection before 2005 and followed up until December 2009. A total 48,010 cases with EV infection and 48,010 healthy controls matched for sex, age, and residence were obtained. Association between EV infection and depression risk was assessed by Cox proportional hazards models to determine the hazard ratios (HRs) and confidence intervals (CIs). We further stratified EV infection into with central nervous system (CNS) involvement and without and compared with matched cohort.Children and adolescents with EV infection had no elevated risk of depression compared with healthy controls (adjusted HR, aHR = 1.00, 95% CI: 0.83-1.21). However, CNS EV infection was associated with increased risk of depression (aHR = 1.62, 95% CI: 1.02-2.58) in the fully adjusted Cox regression model.To the best of our knowledge, this is the first study investigating depression in children and adolescents with CNS EV infection. The results suggested that children and adolescents with CNS EV infection were a susceptible group for subsequent depressive disorders.

Antidepressants and colorectal cancer: A population-based nested case-control study.

BACKGROUND: Experimental evidence indicates that serotonin is associated with both proliferative and pro-carcinogenic effects on colorectal tumors. The present study aims to investigate the associations between antidepressant use and colorectal cancer in an epidemiological sample. METHODS: We conducted a population-based case-control study utilizing Taiwan's National Health Insurance Research Database (NHIRD). We identified 49,342 cases with colorectal cancer and 240,985 controls between 1997 and 2008. We conducted conditional logistic regression analyses to assess the association between antidepressant use and colorectal cancer risk. Sensitivity analyses were conducted to assess whether genotoxic antidepressants (i.e. antidepressants which may exert procarcinogenic effects) would increase risk for colorectal cancer. RESULTS: Selective serotonin reuptake inhibitors (adjusted OR=1.00, 95% CI=0.94-1.06), tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and serotonin antagonist and reuptake inhibitors were not associated with increased incidence of colorectal cancer. Monoamine oxidase inhibitors were, however, associated with an increased incidence of colorectal cancer (adjusted OR=1.22, 95% CI=1.06-1.41). Higher cumulative dose of mirtazapine was associated with a decreased incidence of colorectal cancer (adjusted OR=0.39, 95% CI=0.17-0.90). A small sample size of individuals who received mirtazapine, however, precludes definitive conclusions regarding protective effects with mirtazapine. LIMITATIONS: We could not discern the effects of obesity and other risk factors for colorectal cancer from the NHIRD. CONCLUSIONS: Contemporary first-line antidepressants (i.e. SSRI, SNRI), as well as older agents (i.e. TCA), are not associated with increased incidence of colorectal cancer.

Depression and severity of substance dependence among heroin dependent patients with ADHD symptoms.

BACKGROUND AND OBJECTIVES: Comorbid attention deficit hyperactivity disorder (ADHD) symptoms are highly prevalent among heroin-dependent patients. We aim to investigate differences in dependence severity, depression, and quality of life between heroin-dependent patients with and without ADHD-screened positive. METHODS: Heroin-dependent participants (n = 447) entering methadone maintenance treatment were divided into ADHD-screened positive (ADHD-P) and ADHD-screened negative (ADHD-N) groups according to scores of Adult ADHD Self-Report Scale (ASRS). Mini-International Neuropsychiatric Interview was used to identify current and lifetime depressive episodes and suicidality. Substance use disorder, depression, family support, and quality of life in two groups were also assessed. RESULTS: About 7.8% (n = 35) scored 24 or higher of ASRS indicating highly likely Adult ADHD. More heroin-dependent patients of ADHD-P had a current depressive episode (p = .02). They had higher Center for Epidemiological Studies Depression (CESD) scores (p = .003), and more severe heroin dependence (p = .006). Poorer family support and quality of life in physical, and psychological domains were found in patients of ADHD-P compared to ADHD-N. DISCUSSION AND CONCLUSIONS: Heroin-dependent patients of ADHD-P represent a vulnerable minority. They were comorbid with regard to depression, greater substance dependence severity, and poorer quality of life. SCIENTIFIC SIGNIFICANCE: Assessment for ADHD symptoms in heroin-dependent patients may be indicated for the effective management of the complex problems of these patients. (Am J Addict 2017;26:26-33).

Chronic obstructive pulmonary disease and anxiety disorders: a nationwide population-based study in Taiwan.

OBJECTIVE: Few studies have investigated the relationship between chronic obstructive pulmonary disease (COPD) and anxiety disorder outcomes. We sought to investigate the association in a large national sample. METHODS: Cases were identified from Taiwan's National Health Insurance Research Database who were aged 15 years and above, with a new primary diagnosis of COPD (International Classification of Diseases, Ninth Revision codes: 491, 492, 494 and 496) between 2000 and 2007. The 29,951 cases identified were compared to 29,951 controls matched on sex, age, urban/rural residence and socioeconomic status based on insurance premium. Both groups were followed until the end of 2008 for instances of anxiety disorders. Competing risk-adjusted Cox regression analyses were applied, adjusting for matching variables, Charlson comorbidity index, hospital admission days and daily dose of prednisone. RESULTS: Of the 59,902 subjects, 3951 were found to have anxiety disorders during a mean (SD) follow-up period of 5.5 (2.5) years. COPD, female, urban residence, lower dose of prednisone use, depressive disorders and higher outpatient visits were independent predictors of incident anxiety disorder. CONCLUSIONS: COPD was associated with increased risk of an anxiety disorder diagnosis, independent of a number of potential confounding factors.

Assessment of abnormal brain structures and networks in major depressive disorder using morphometric and connectome analyses.

BACKGROUND: It is hypothesized that the phenomenology of major depressive disorder (MDD) is subserved by disturbances in the structure and function of brain circuits; however, findings of structural abnormalities using MRI have been inconsistent. Generalized q-sampling imaging (GQI) methodology provides an opportunity to assess the functional integrity of white matter tracts in implicated circuits. METHODS: The study population was comprised of 16 outpatients with MDD (mean age 44.81±2.2 years) and 30 age- and gender-matched healthy controls (mean age 45.03±1.88 years). We excluded participants with any other primary mental disorder, substance use disorder, or any neurological illnesses. We used T1-weighted 3D MRI with voxel-based morphometry (VBM) and vertex-wise shape analysis, and GQI with voxel-based statistical analysis (VBA), graph theoretical analysis (GTA) and network-based statistical (NBS) analysis to evaluate brain structure and connectivity abnormalities in MDD compared to healthy controls correlates with clinical measures of depressive symptom severity, Hamilton Depression Rating Scale 17-item (HAMD) and Hospital Anxiety and Depression Scale (HADS). RESULTS: Using VBM and vertex-wise shape analyses, we found significant volumetric decreases in the hippocampus and amygdala among subjects with MDD (p<0.001). Using GQI, we found decreases in diffusion anisotropy in the superior longitudinal fasciculus and increases in diffusion probability distribution in the frontal lobe among subjects with MDD (p<0.01). In GTA and NBS analyses, we found several disruptions in connectivity among subjects with MDD, particularly in the frontal lobes (p<0.05). In addition, structural alterations were correlated with depressive symptom severity (p<0.01). LIMITATIONS: Small sample size; the cross-sectional design did not allow us to observe treatment effects in the MDD participants. CONCLUSIONS: Our results provide further evidence indicating that MDD may be conceptualized as a brain disorder with abnormal circuit structure and connectivity.

Risk of bipolar disorder in patients with COPD: a population-based cohort study.

BAKCGROUND: Few studies have investigated the relationship between chronic obstructive pulmonary disease (COPD) and bipolar outcomes in the world. We sought to investigate the association between COPD and risk of bipolar disorder in a large national sample. METHODS: The insured aged 15 years or more with a new primary diagnosis of COPD (ICD-9: 491, 492, 494 and 496) between 2000 and 2007 were identified from Taiwan's National Health Insurance Research Database. We included individuals with an inpatient diagnosis of COPD and/or at least 1 year of two diagnoses of COPD in outpatient services. These 35,558 cases were compared to 35,558 sex-, age-, residence- and insurance premium-matched controls. We followed both groups until the end of 2008 for incidence of bipolar disorder, defined as ICD-9 codes 296.0-296.16, 296.4-296.81 and 296.89. Competing risk-adjusted Cox regression analyses were applied with adjusting for sex, age, residence, insurance premium, prednisone use, Charlson comorbidity index, diabetes, hypertension, hyperlipidemia, cardiovascular diseases, hospital admission days, outpatients' visits and mortality. RESULTS: Of the total 71,116 subjects, 202 were newly diagnosed with bipolar disorder during the study period. The mean follow-up time was 6.0 (SD=2.2) years. COPD, younger age, lower economic status, lower dose of prednisone use, higher hospital admission days and higher outpatient visits were independent predictors of bipolar disorder. CONCLUSIONS: COPD was associated with increased risk of bipolar disorder independent of a number of potential confounding factors in this study.

Relationship between antidepressant prescription and breast cancer: a population based study in Taiwan.

OBJECTIVE: To investigate the association between antidepressant prescription and breast cancer. METHODS: The National Health Research Institute in Taiwan provided a database of 1 000 000 random subjects for this study. We identified 14 737 new antidepressant female users who were more than 15 years old during 1999-2005 with at least 10 prescriptions and one year exposure to an antidepressant. These were matched 1:1 by age and residence to non-antidepressant users from the same database to compare the risk of breast cancer. RESULTS: In a model adjusted by age, residence, insurance amount, and depressive disorder, antidepressant prescription was not associated with breast cancer risk. This held true for both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants. CONCLUSIONS: There was no evidence for an association between antidepressant prescription and the risk of breast cancer. Copyright © 2015 John Wiley & Sons, Ltd.