Effects of short-term exposure to air pollution on hospital admissions for autism spectrum disorder in Korean school-aged children: a nationwide time-series study.

OBJECTIVES: This study explored the effects of short-term exposure to air pollution on hospital admissions for autism spectrum disorder (ASD), a proxy for symptom aggravation, among Korean children aged 5-14 years. DESIGN: Time-series study. SETTING, PARTICIPANTS AND OUTCOME MEASURES: We used data from the National Health Insurance Service (2011-2015). Daily concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2) and ozone (O3) levels in each region were used as exposures. ASD cases were defined based on a principal admission diagnosis of the claims data. We applied distributed lag non-linear models and a generalised difference-in-differences method to the quasi-Poisson models to estimate the causal effects of air pollution for up to 6 days. We also performed weighted quantile sum regression analyses to assess the combined effects of air pollution mixtures. RESULTS: PM2.5 levels at lag day 1, NO2 levels at lag day 5 and O3 levels at lag day 4 increased the risks of hospital admissions for ASD (relative risk (RR)=1.17, 95% CI 1.10 to 1.25 for PM2.5; RR=1.09, 95% CI 1.01 to 1.18 for NO2 and RR=1.03, 95% CI 1.00 to 1.06 for O3). The mean daily count of hospital admissions for ASD was 8.5, and it would be 7.3, 7.8 and 8.3 when the PM2.5 levels would be decreased by 10.0 µg/m3, NO2 by 10 ppb and O3 by 10 ppb, respectively. The weighted quantile sum index, constructed from PM2.5, NO2 and O3 levels, was associated with a higher risk of hospital admissions for ASD (RR 1.29, 95% CI 1.14 to 1.46), where NO2 was found to contribute to the effects most (the weight of 0.80). CONCLUSIONS: These results emphasise that reduction of air pollution exposure should be considered for ASD symptom management, with important implications for the quality of life and economic costs.

Association between short-term air pollution exposure and attention-deficit/hyperactivity disorder-related hospital admissions among adolescents: A nationwide time-series study.

Long-term air pollution exposure has been suggested to increase the risk of attention-deficit/hyperactivity disorder (ADHD). However, the association between short-term air pollution exposure and ADHD-related outcomes is still unknown. We investigated the associations between short-term exposure to particulate matter with an aerodynamic diameter ≤10 µm (PM10), nitrogen oxide (NO2), and sulfur dioxide (SO2) and hospital admissions with a principal diagnosis of ADHD among adolescents (age 10-19 years) in 16 regions of the Republic of Korea from 2013 to 2015. We estimated the region-specific relative risks (RRs) and 95% confidence intervals (CIs) from quasi-Poisson regressions adjusted for potential confounders, considering single-day and moving average lag. Consequently, we performed meta-analyses to pool the region-specific estimates. The risks of ADHD-related hospital admissions were increased in the single-day and moving average lag models for PM10 (largest association for lag 1 in the single-day lag model, RR = 1.12, 95% CI: 1.05, 1.20; lag 0-2 in the moving average lag model, RR = 1.17, 95% CI: 1.07, 1.27), NO2 (lag 3, RR = 1.47, 95% CI: 1.25, 1.73; lag 1-3, RR = 1.68, 95% CI: 1.38, 2.04), and SO2 (lag 1, RR = 1.27, 95% CI: 1.14, 1.41; lag 1-3, RR = 1.29, 95% CI: 1.12, 1.49). The associations were similar between boys and girls, but they were stronger among adolescents aged 15-19 years than those aged 10-14 years for NO2 and SO2. In conclusion, the results indicate that short-term exposure to PM10, NO2, and SO2 may be a risk factor for the exacerbation of ADHD symptoms, leading to hospitalization.

Modification of the Association between Visual Impairment and Mortality by Physical Activity: A Cohort Study among the Korean National Health Examinees.

The association between visual impairment and higher mortality remains unclear. In addition, evidence is lacking on the interaction between visual function and physical activity on mortality. We used data of individuals with no disability or with visual impairment among those who participated in the National Health Screening Program in Korea in 2009 or 2010. We constructed Cox proportional hazard models adjusted for potential confounders to evaluate the independent association between visual impairment and mortality. More severe visual impairment was associated with higher all-cause mortality (p-value for trend = 0.03) and mortality due to cardiovascular diseases (p-value for trend = 0.02) and that due to other diseases (p-value for trend = 0.01). We found an interaction on an additive scale between visual impairment and no physical activity on all-cause mortality (relative excess risk due to interaction = 1.34, 95% confidence interval: 0.37, 2.30, p-value = 0.01). When we stratified the study population by physical activity, the association between visual impairment and mortality was only found among individuals who did not engage in regular physical activity (p-value for trend = 0.01). We found an independent association between visual impairment and mortality and modification of this association by physical activity.

Healthcare access challenges facing six African refugee mothers in South Korea: a qualitative multiple-case study.

PURPOSE: Following legal reform in 2013, the annual number of asylum seekers entering South Korea has increased from 1,143 in 2012 to 5,711 in 2015. We interviewed six African refugee mothers of young children regarding their health needs and barriers to access maternal child health services. METHODS: We recruited mothers who had visited a clinic for immigrants between July 2013 and August 2015. Participants were African refugee women, aged over 18 years, who had given birth in Korea within the previous 5 years and had come to Korea over a year before recruitment. Interview questions examined participants' experiences in pregnancy and childbirth and concerns regarding their child's health status. Initial data analysis involved all researchers' immersion in the entire collection of transcripts. We then noted recurrent topics and themes and identified similar issues. RESULTS: At the time of giving birth, 5 participants were asylum seekers and one had undocumented status. The following barriers impeded their access to maternal child healthcare: socioeconomic factors (unstable social identity, low economic status, difficulty obtaining health insurance), language barriers (lack of linguistically appropriate health information, limited access to translation services), and cultural barriers (religious and cultural differences). Weak social support also hindered access to healthcare soon after migration; however, social links with the community emerged as a key coping strategy following settlement. CONCLUSION: We identified barriers to maternal and child healthcare and coping strategies among African refugee mothers in Korea. Future research should assess refugees' health status and improve health access and literacy among refugee mothers.

Association between personality traits and mental health outcomes in older adults with lifetime trauma exposure: a nationwide community sample.

BACKGROUND: This study evaluated the impacts of earlier traumatic events on the mental health of older adults, in terms of mental disorders and mental well-being, according to sociodemographic variables, trauma-related characteristics, and personality traits in a nationally representative sample of older Koreans. METHODS: A total of 1,621 subjects aged 60 to 74 years from a Korean national epidemiological survey of mental disorders responded face-to-face interviews. The Korean Composite International Diagnostic Interview was used to investigate lifetime trauma exposure (LTE) and psychiatric diagnoses. The EuroQol health classification system and life satisfaction scale were used to assess quality of life (QoL), and the Big Five Inventory-10 (BFI-10) to measure personality traits. RESULTS: Five-hundred and seventy-seven subjects (35.6%) reported a history of LTE (mean age at trauma, 30.8 years old). Current mental disorders were more prevalent in elderly people with LTE, while better current QoL was more frequent in those without LTE. Among older people with LTE, lower extraversion and higher neuroticism increased the risk of current mood or anxiety disorders, whereas higher extraversion increased the probability of experiencing mental well-being after adjusting for sociodemographic and trauma-related variables. CONCLUSION: Personality traits, especially extraversion, and neuroticism, may be useful for predicting the mental health outcomes of LTE in older adults. Further longitudinal studies investigating the relationship between traumatic events and mental health outcomes are needed.

General Similarities but Consistent Differences Between Early- and Late-Onset Depression Among Korean Adults Aged 40 and Older.

Differences in clinical characteristics, symptomatology, and psychiatric comorbidity between early-onset depression (EOD) and late-onset depression (LOD) were examined in a nationwide representative sample. The Korean Composite International Diagnostic Interview was used to investigate psychiatric diagnoses and age of onset. A total of 319 subjects aged 40 years and older with a current major depressive disorder (MDD) were included, and both a continuous and a dichotomous (40 years) age-of-onset indicator were used in the analyses. Despite general similarities between groups, EOD was related to chronic (recurrent and longer episode) and severe (higher lifetime suicidality) clinical features. Hypersomnia and suicidal plans/attempts were associated with EOD, whereas anhedonia was related to LOD. Lifetime generalized anxiety disorder was associated with EOD, whereas dysthymic disorder was related with higher age of MDD onset. This study provides additional evidence of consistent differences between EOD and LOD among middle-aged and older Asians.

Prevalence of Sexual Dysfunction and Associations with Psychiatric Disorders Among Women Aged 50 and Older.

OBJECTIVE: This study investigated the prevalence of sexual problems and associated factors, focusing particularly on comorbid psychiatric disorders, among older Korean women. METHODS: A nationally representative sample of women aged 50-74 years (n=3828) responded to in-person interviews using the Korean version of the Composite International Diagnostic Interview to assess psychiatric disorders and four symptoms of sexual dysfunction: (1) lack of sexual interest/sexual aversion, (2) dyspareunia, (3) loss of pleasure, and (4) other organic dysfunction (e.g., inability of sexual arousal). We examined the likelihood of sexual dysfunction by sociodemographic and clinical variables, including specific psychiatric disorders, and compared the characteristics of sexual dysfunction among women with and without a comorbid psychiatric disorder. RESULTS: A total of 334 (8.7%) women reported one or more symptoms of sexual dysfunction during the year preceding the interview: lack of sexual interest/sexual aversion was most prevalent (7.7%), followed by loss of pleasure (4.2%), dyspareunia (2.4%), and other organic dysfunction (0.4%). Having a psychiatric disorder was associated with a 2.7-fold increase in the probability of sexual dysfunction. Among women with sexual dysfunction, having comorbid mental disorder was associated with being unmarried status, a symptom of loss of pleasure, and a history of sexual dysfunction before 50 years of age. CONCLUSIONS: The present study suggests a relatively lower prevalence of sexual dysfunction than previously reported, but supports its strong association with psychiatric disorders among postmenopausal women. We should evaluate comorbid mental disorder with sexual dysfunction, especially among those having some characteristics.

Ten-year trends in the prevalence and correlates of major depressive disorder in Korean near-elderly adults: a comparison of repeated nationwide cross-sectional studies from 2001 and 2011.

PURPOSE: Near-elderly adults go through many changes in socioeconomic status, such as retirement, which may affect their mental health differently according to when they live. We aimed to compare the prevalence of major depressive disorder (MDD) and its changes according to sociodemographic factors using nationally representative surveys of Korean near-elderly adults conducted 10 years apart. METHODS: Nationwide community samples of individuals aged 55-64 years living in 2001 (n = 1256) and 2011 (n = 1066) were compared. Face-to-face interviews were conducted using the Korean version of the Composite International Diagnostic Interview to diagnose MDD. Sociodemographic data were collected using self-reported questionnaires including questions on employment and economic status. We examined differences in MDD prevalence and its association with sociodemographic factors over time by calculating 2011-to-2001 odds ratios (ORs) using multivariable logistic regression models. RESULTS: Among near-elderly people, MDD tended to be more prevalent in 2011 than in 2001. However, only near-elderly men in 2011 showed a higher risk of MDD compared with those in 2001 (2011-to-2001 OR 4.19), while women did not. The prevalence ratio by gender decreased from 7.04 in 2001 to 2.34 in 2011. Among vulnerable sociodemographic groups, a significant increase in MDD was observed in unemployed men (adjusted OR 8.35), but not in unemployed women or other vulnerable groups. CONCLUSION: This study provides evidence of a substantial increase in MDD in Korean near-elderly men and suggests that unemployment should be considered as an important correlate of MDD in this group.

Age-related differences in the influence of major mental disorders on suicidality: a Korean nationwide community sample.

BACKGROUND: We compared the influence of major mental disorders on suicidality according to age, adjusting for suicide-related correlates. METHODS: This study was based on the Korean national epidemiological survey of mental disorders including community-dwelling adults between 18 and 74 years of age (n=6022). Subjects were classified into three age groups; young (18-39), middle-aged (40-59), and late adulthood (60-74). Face-to-face interviews were conducted using the Korean version of the Composite International Diagnostic Interview. According to age groups, the influence of major depressive disorder (MDD), anxiety disorder, and alcohol use disorder on risk for suicidality were investigated by multiple logistic regression models adjusting for sex, years of education, marital status, income, employment, presence of chronic medical illness, and lifetime history of suicide attempt. RESULTS: After including MDD as a covariate, anxiety disorder remained a risk factor only in the middle-aged group (adjusted OR: 2.83, 95% CI: 1.54-5.22), and alcohol use disorder was a risk factor for suicidality only in the young group (adjusted OR: 2.81, 95% CI: 1.06-7.43). Conversely, MDD was the only mental disorder that significantly increased suicidality in all age groups. LIMITATIONS: This was a cross-sectional study and did not include subjects over 75 years of age. CONCLUSION: This study showed that the contribution of psychiatric disorders to risk for suicidality varied according to age group. Therefore, strategies for suicide prevention should be specifically designed for different age groups.

Human serum transthyretin levels correlate inversely with Alzheimer's disease.

Alzheimer's disease (AD) is the fastest growing neurodegenerative disease in the elderly population, and the search for therapeutic targets and diagnostic AD biomarkers is an exigent issue. Because amyloid-ß (Aß) aggregation constitutes the epicenter of AD pathology, Aß-binding proteins that regulate Aß aggregation, such as transthyretin (TTR), have attracted much attention. TTR binds to Aß, prevents its aggregation, and consequently inhibits Aß-induced cellular toxicity. Decreased TTR levels in cerebrospinal fluid (CSF) from AD patients suggest that TTR is a biomarker of AD. But, studies on TTR as a biomarker have focused on CSF; no study has evaluated peripheral levels of TTR in AD. Here, we examined the relationship between serum TTR levels and AD. We measured TTR levels in serum samples from 90 nondemented controls and 111 AD patients and observed significantly lower serum TTR levels in AD (p < 0.001). Notably, females in the control group had lower serum TTR levels compared with male in the control (p = 0.006), while no difference in gender was noted in the AD group. There were no age-related changes in serum TTR levels. Thus, this study demonstrates a clear negative correlation between serum TTR levels and AD, suggesting that TTR is not only involved in AD pathological process but also suggested as possible peripheral biomarker for AD diagnosis in serum level.

Identification of autoantibody against beta-amyloid peptide in the serum of elderly.

Alzheimer's disease (AD) is characterized by two major neurological features: amyloid deposits and neurofibrillary tangles in the brain. According to the amyloid cascade hypothesis, accumulation of amyloid-beta peptide (A-beta) plays a central role in the pathogenesis of AD. Several lines of evidence suggest that antibodies against A-beta play a protective role in the neuropathology of AD. In this study, we describe the purification of an autoantibody against A-beta from human serum using affinity purification method. The purified autoantibody recognized A-beta deposits in the brain of aged Tg2676 mice, an animal model of AD. The serum levels of anti-A-beta autoantibody correlated inversely with age in both AD patients and control non-demented elderly subjects. Furthermore, the levels were significantly lower in AD patients compared with the age-matched control subjects. It is the first time to show the identification of endogenous anti-A-beta autoantibody in human serum and suggesting that serum levels of anti-A-beta autoantibody might be a good biomarker for AD patients.

Rac1 changes the substrate specificity of gamma-secretase between amyloid precursor protein and Notch1.

Beta amyloid peptide is generated from amyloid precursor protein (APP) by proteolytic cleavage of beta- and gamma-secretases, and plays a critical role in the pathogenesis of Alzheimer's disease. Since gamma-secretase cleaves several proteins including APP and Notch in a number of cell types, it is important to understand the conditions determining gamma-secretase substrate specificity. In the present study, inhibition of Rac1 attenuated gamma-secretase activity for APP, resulting in decreased production of the APP intracellular domain but accumulated C-terminal fragments (APP-CTF). In contrast, Rac1 inhibitor, NSC23766 increased production of the Notch1 intracellular domain but slightly decreased the ectodomain-shed form of Notch1 (NotchDeltaE). To elucidate the mechanism underlying these observations, we performed co-immunoprecipitation experiments to analyze the interaction between Rac1 and presenilin1 (PS1), a component of the gamma-secretase complex. Inhibition of Rac1 enhanced its interaction with PS1. Under the same condition, PS1 interacted more strongly with NotchDeltaE than with APP-CTF. Our results suggested that PS1 determines the preferred substrate for gamma-secretase between APP and Notch1, depending on the activation status of Rac1.

Reduced serum level of antibodies against amyloid beta peptide is associated with aging in Tg2576 mice.

Both active and passive immunization to eliminate amyloid plaques from the brain of patients with Alzheimer's disease (AD) have confirmed that amyloid beta (Abeta) vaccination does not only result in clearance of Abeta plaques but improves behavioral-cognitive deficits in animal models of AD. In the present study, the levels of naturally occurring serum antibodies against Abeta were measured in Tg2576 mice at various ages using ELISA to determine the relationship between aging and the level of anti-Abeta autoantibody. The level of anti-Abeta antibody fell significantly at the age of 9 months, at the age when amyloid plaques started to appear in the brain of Tg2576 mice, and was persistently low thereafter. However, serum immunoglobulin (Ig) level was elevated in older transgenic mice compared with younger transgenic mice suggesting that the reduced level of anti-Abeta autoantibody was not merely due to deterioration of the immune response in aged Tg2576 mice.

Bis-styrylpyridine and bis-styrylbenzene derivatives as inhibitors for Abeta fibril formation.

New bis-styrylpyridine and bis-styrylbenzene derivatives were designed and synthesized. These 34 compounds were evaluated by Abeta fibril formation inhibitory assay using thioflavin T as a dye (named ThT assay). Most of them showed excellent inhibitory activities for Abeta fibril formation at IC50 of 0.1-2.7 microM which is comparable to curcumin (IC50 of 0.8 microM). Among them, nine compounds were screened for their cytotoxicities on HT-22 cell by MTT assay at 1, 10, and 50 microM. In particular, I-7 and II-2 exhibited the best combination of inhibitory activity and compound cytotoxicity.

Furin is an endogenous regulator of alpha-secretase associated APP processing.

Constitutive and PKC-regulated alpha-secretase pathways have been reported to produce the secreted form of alpha-secretase-derived APP (sAPPalpha). Here, we examined putative role of furin in the regulation of alpha-secretase activity in vitro and in vivo. Overexpression of the prodomain of furin and infection with a furin-specific inhibitor significantly reduced the levels of sAPPalpha regardless of PKC activity, whereas total APP levels remained unchanged. Furin mRNA levels in the brains of AD patients and Tg2576 mice were significantly lower than those in controls, whereas ADAM10 and TACE mRNA levels were much alike between Tg2576 and littermate mice. Moreover, the injection of furin-adenovirus into Tg2576 mouse brains markedly increased alpha-secretase activity and reduced beta-amyloid protein (Abeta) production in infected brain regions. Our results suggest that furin enhances alpha-secretase activity via the cleavage of ADAM10 and TACE, and that attenuated furin activity is connected to the production of Abeta.