Yin-To Liao

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.

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

Abstract 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.

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).

Asthma and self-harm: A population-based cohort study in Taiwan

OBJECTIVE Few studies have investigated the relationship between asthma and suicidality-related outcomes in the world. We sought to investigate the association between asthma and risk of non-fatal self-harm in a large national sample. METHODS Cases aged 10years and over were identified from Taiwans National Health Insurance Research Database with a new primary diagnosis of asthma (ICD-9:493) between 2000 and 2008. Case status required the presence of any inpatient diagnosis of asthma and/or at least two recorded diagnoses and 1year duration of asthma in outpatient services. These 27,781 cases were compared to 138,905 sex- and age-matched controls and both groups were followed until end of 2008 for instances of self-harm, defined as ICD-9 codes E950-E959 (self-harm causes) and E980-E989 (undetermined causes). Competing risk adjusted Cox regression analyses were applied, adjusting for sex, age, residence (urban/rural), insurance premium, episode of psychiatric disease, montelukast, Charlson comorbidity index and mortality. RESULTS Of the 166,686 subjects, 445 carried out self-harm during a mean (SD) follow-up period of 5.84 (2.35) years. Asthma (hazard ratio=1.70, 95% CI: 1.35-2.14), age, residence, episode of psychiatric disease and Charlson comorbidity index were independent risks on self-harm in the fully adjusted model. CONCLUSIONS Asthma was associated with increased risk of self-harm in this population, independent of a number of potential confounding factors including montelukast use. This reinforces the need to consider mental health in routine asthma care, and to consider asthma as a potentially important stressor in people with comorbid mental disorder.

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.].

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

To investigate the association between antidepressant prescription and breast cancer.

Correlation between brain circuit segregation and obesity

HighlightsIn voxel‐based morphometry, the obese patients showed altered gray matter volumes in the amygdala, thalamus and putamen.The obesity group showed increased functional connectivity in the bilateral anterior cingulate cortex.The obesity group showed 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 graph theoretical analysis, the obese patients showed a shift toward randomization in their functional networks. Abstract 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.

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 Taiwans 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.

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 Taiwans 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.