Healthcare Utilization, Physical and Psychiatric Comorbidities Before Self-Injurious Behavior in Patients with Asthma: A Nested Case-Control Study.

Background: Patients with asthma experience more physical, psychological, and financial burdens; a link between asthma and suicidality has been reported in research. Purpose: This study analyzed the medical utilization and comorbidity before their self-injurious behavior in patients with asthma. Methods: We enrolled 186,862 patients newly diagnosed with asthma between 1999 and 2013 from the National Health Insurance Research Database in Taiwan. A total of 500 case subjects had ever conducted self-injurious behaviors during the study period. Based on a nested case-control study, each case was matched with 10 controls derived from the asthma cohort to analyze differences between them and their medical use models. Results: The results indicated that, compared to the control group, the cases presented higher frequencies of outpatient visits and hospitalizations. Regarding comorbidity, the cases had more cardiovascular diseases (adjusted odds ratio [aOR]=1.58; p<0.001), bipolar disorder (aOR=2.97; p<0.001), depression (aOR=4.44; p<0.001), and sleep disorder (aOR=1.83; p<0.001) than the controls. Conclusion: The evidence-based information serves as a reference for medical staff to reduce the occurrence of self-injurious behavior in patients with asthma.

Exposome of attention deficit hyperactivity disorder in Taiwanese children: exploring risks of endocrine-disrupting chemicals.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is diagnosed in ~7% of school-aged children. The role of endocrine-disrupting chemicals (EDC) and oxidative stress in ADHD etiology are not clear. OBJECTIVE: Assessment of the associations between simultaneous exposure to multiple compounds and ADHD in children. METHODS: The case-control study included 76 clinically diagnosed ADHD cases and 98 controls, aged 4-15 years old. Concentrations quartiles of urinary metabolites of acrylamide, acrolein, nonylphenol, phthalates, and organophosphate pesticides and biomarkers of oxidative stress were used to fit logistic regressions for each compound and weighted quantiles sum (WQS) regression for the mixture. RESULTS: Positive dose-response relationships with ADHD were observed for 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) (odds ratio(OR)Q4 = 3.73, 95%CI [1.32, 11.04], ptrend = 0.003), dimethyl phosphate (DMP) (ORQ4 = 4.04, 95%CI [1.34, 12.94], ptrend = 0.014) and diethyl phosphate (ORQ4 = 2.61, 95%CI = [0.93, 7.66], ptrend = 0.030), and for the mixture of compounds (ORWQS = 3.82, 95%CI = [1.78, 8.19]) with the main contributions from HNE-MA (28.9%) and DMP (18.4%). CONCLUSIONS: The dose-response relationship suggests enhanced susceptibility to EDC burden in children even at lower levels, whereas the main risk is likely from organophosphate pesticides. HNE-MA is recommended as a sensitive biomarker of lipid peroxidation in the further elucidation of the oxidative stress role in ADHD etiology.

The associations among organophosphate pesticide exposure, oxidative stress, and genetic polymorphisms of paraoxonases in children with attention deficit/hyperactivity disorder.

This study will help to clarify the relationship between organophosphate pesticides (OPs) and attention deficit/hyperactivity disorder (ADHD) related to oxidative stress and paraoxonases (PON) polymorphisms to further characterize the gene-environment interaction. This case-control study enrolled 85 children with ADHD and 96 control subjects. Urinary OP levels were analyzed by using gas chromatography-mass spectrometry (GC-MS). Oxidative stress biomarkers, such as 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2-Gua), 8-iso-prostaglandin F2α (8-iso-PGF2α), and 4-hydroxy-2-nonenoic acid-mercapturic acid (HNE-MA), were analyzed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S) were calculated to evaluate the additive interactions between OP exposure and PON genetic polymorphism on ADHD. A causal mediation analysis was conducted to clarify the mediation effects of oxidative stress due to OP exposure on ADHD. Children with ADHD had significantly higher DMP (238.95 nmol/g cre. vs. 164.83 nmol/g cre., p value = 0.01) and HNE-MA (30.75 µg/g cre. vs. 18.41 µg/g cre., p value<0.01) concentrations than control children. Children who carried the PON1 GG genotype (rs705379) had low urinary DMP levels, and the level increased with increasing numbers of allele variants. The risk for developing ADHD reached 2.06-fold (OR = 2.06, 95% CI:1.23-3.44) and 1.43-fold (OR = 1.45, 95% CI:1.04-2.03) when the DMP and HNE-MA levels increased by 1 natural log of the concentration, respectively. The estimated AP value was 0.66 (95% CI: 0.17-1.15), indicating that 66% of ADHD cases in DMP-exposed children with the PON1 CT/TT (rs705381) genotype were due to gene-environment interactions. No significant mediation of HNE-MA was observed between DMP exposure and the risk of ADHD. The estimated proportion mediated was only 7.0% (95% CI: -0.08-0.46). This research suggests the role of OP exposure in the occurrence of ADHD after adjusting for covariates.

The interactions among organophosphate pesticide exposure, oxidative stress, and genetic polymorphisms of dopamine receptor D4 increase the risk of attention deficit/hyperactivity disorder in children.

OBJECTIVE: The aim of this study was to clarify the association between organophosphate pesticides (OPs) and attention-deficit/hyperactivity disorder (ADHD) related to oxidative stress and genetic polymorphisms. METHODS: This case-control study enrolled 93 children with ADHD and 112 control children in north Taiwan. Six dialkyl phosphate (DAP) metabolites of OPs and oxidative stress biomarkers were analyzed. Polymorphisms of the dopamine receptor D4 gene (DRD4) were identified. RESULTS: Children with ADHD had significantly higher dimethylphosphate (DMP, 236.69nmol/g cre. vs. 186.84nmol/g cre., p value = 0.01) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA, 28.95µg/g cre. vs. 16.55µg/g cre., p value<0.01) concentrations than control children. Children who carried DRD4 GA/AA genotypes (rs752306) were less likely than those who carried the DRD4 GG genotype to have ADHD (odds ratio [OR]: 0.45, 95% CI: 0.24-0.84). The estimated value of the AP (attributable proportion due to interaction) was 0.59 (95% CI: 0.13-1.05), indicating that 59% of ADHD cases in DMP-exposed children with the DRD4 GG genotype were due to the gene-environment interaction. After adjustment for other covariates, children who carried the DRD4 GG genotype, had been exposed to high DMP levels (more than the median), and had high HNE-MA levels had a significantly increased risk for developing ADHD (OR = 11.74, 95% CI: 2.12-65.04). CONCLUSION: This study indicated a gene-environment interaction in the risk of ADHD in children. The association between DMP and ADHD in children might relate to the mechanism of lipid peroxidation. Dose-response relationships and the combined effects of OPs, oxidative stress, and genetic polymorphism on ADHD should not be neglected.

Sugar-Sweetened Beverage Consumption Is Adversely Associated with Childhood Attention Deficit/Hyperactivity Disorder.

Attention deficit/hyperactivity disorder (ADHD) is one of the most common childhood neurobehavioral conditions. Evidence of the negative effects of sugar-sweetened beverages (SSBs) on mental health has not been convincing, although a few studies have found an association between high SSB levels and attention problems in children. This study aimed to test the hypothesis that SSB consumption is associated with ADHD among children. Doctor-diagnosed ADHD cases (n = 173) and non-ADHD controls (n = 159) between age 4 to 15 were recruited. SSB consumption, socio-demographic and lifestyle characteristics of the children, as well as of their mothers' characteristics during pregnancy, were collected using a questionnaire. Blood lead levels and polymorphisms of two commonly verified dopaminergic-related genes (the D4 dopamine receptor gene DRD4 and the dopamine transporter gene DAT1) were also analyzed. There was a dose-response relationship between SSB consumption and ADHD. After covariates were adjusted, children who consumed SSBs at moderate levels and high levels had 1.36 and 3.69 odds, respectively, of having ADHD, compared with those who did not consume SSBs (p for trend < 0.05). Similar results were obtained when females were excluded. Our findings highlighted the adverse correlation between SSB consumption and ADHD and indicated a dose-response effect even after covariates were adjusted.

Attention Deficit/Hyperactivity Disorder and Urinary Nonylphenol Levels: A Case-Control Study in Taiwanese Children.

OBJECTIVE: Nonylphenol (NP) belongs to the family of endocrine disruptors, and it is widely used in industrial applications and is ubiquitous in daily foods. Animal studies have suggested that NP exposure might promote motor hyperactivity, likely by causing deficits in dopaminergic neurons. However, research assessing NP exposure and epidemiology studies on human populations are limited. The aim of this study was to explore the association between child NP exposure and ADHD while considering particular covariants, such as lead levels and dopamine-related gene variations. METHODS: A case-control study was conducted on patients with clinically diagnosed ADHD; the Swanson, Nolan and Pelham, Fourth Revision (SNAP-IV) questionnaire was used to identify normal controls aged 4-15 years. Participants were examined for urinary NP concentrations, blood lead levels, and select single-nucleotide polymorphisms of two dopamine-related genes (D4 dopamine receptor, DRD4, and dopamine transporter, DAT1). Socio-demographic variables, maternal lifestyle factors during pregnancy and family medical history were obtained using a questionnaire. RESULTS: A total of 97 children with doctor-diagnosed ADHD and 110 normal controls were enrolled. The blood lead levels in both groups were similar (1.57±0.73 vs. 1.73±0.77 µg/dL, p = 0.15). No significant difference in urinary NP concentration was found between the children with ADHD and the control subjects (4.52±3.22 µg/g cr. vs. 4.64±2.95 µg/g cr., p = 0.43). ADHD was significantly more prevalent among males in this study (male to female ratio: 5:1 for the ADHD group and 1.3:1 for the control group, p<0.01). The analysis was repeated after excluding the females, but this had no effect on the association between NP and ADHD. The regression model, including or excluding females, indicated no increased odds of having ADHD in the context of NP exposure after adjusting for covariants. CONCLUSION: This study indicated that NP exposure might not promote ADHD in children, even though children in Taiwan had relatively high levels of NP compared to those reported previously and those in developed nations.

Anxiety, depressive symptom and suicidal ideation of outpatients with obsessive compulsive disorders in Taiwan.

AIMS AND OBJECTIVES: The major aims of this study were to explore the differences in anxiety, depressive symptoms and suicidal ideation between high and low obsessive compulsive symptom groups, as well as predictors for suicidal ideation among outpatients with obsessive compulsive disorder. BACKGROUND: Obsessive compulsive disorder is often accompanied by anxiety, depression and even suicidal ideation. However, there have been very few studies exploring the inter-relationships among anxiety, depressive symptoms and suicidal ideation for patients with obsessive compulsive disorder. DESIGN: This study employed a cross-sectional comparative research design. METHODS: A sample of 128 outpatients with obsessive compulsive disorder was recruited from a medical teaching hospital in Northern Taiwan. The major study instruments included the Beck Anxiety Inventory, Beck Depression Inventory II, Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Beck Scale for Suicide Ideation. We divided outpatients into two groups: outpatients with Y-BOCS scores higher than 15 were placed in the high obsessive compulsive symptom group, while outpatients with Y-BOCS score lower than or equal to 15 were placed in the low obsessive compulsive symptom group. Statistical methods included Pearson's product-moment correlation, independent samples t-test, chi-square test and multiple regressions. RESULTS: Results revealed that obsessive compulsive disorder outpatients with high Y-BOCS scores also had higher rates of being single and having an earlier onset age, poorer disease control, higher levels of anxiety, depressive symptoms and suicidal ideation. The predictors for suicidal ideation were anxiety and depressive symptoms. CONCLUSIONS: Obsessive compulsive disorder patients with higher obsessive compulsive symptoms are at greater risk of higher levels of anxiety, depressive symptoms and suicidal ideation. In addition to depression, anxiety symptoms contribute significantly to suicidal ideation among patients with obsessive compulsive disorder. RELEVANCE TO CLINICAL PRACTICE: Standard nursing care of patients with obsessive compulsive disorder should incorporate assessing levels of obsessive compulsive symptoms to identify the severity of anxiety, depressive symptoms and suicidal ideation more accurately.