Background Many potential environmental risk and protective factors, and peripheral biomarkers for ADHD have been investigated, but their consistency and magnitude are unclear. We aimed to systematically appraise the published evidence of association between potential risk factors, protective factors, or peripheral biomarkers, and ADHD. MethodsWe did an umbrella review of meta-analyses. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews from inception to Oct 31, 2019, and screened the references of relevant articles. We included systematic reviews providing meta-analyses of observational studies that examined associations of potential environmental risk factors, protective factors, or peripheral biomarkers with diagnosis of ADHD. We included meta-analyses using categorical ADHD diagnosis criteria according to DSM, or hyperkinetic disorder according to ICD, and accepted less rigorous criteria such as self-reports. We excluded articles that did not examine environmental risk factors, protective factors, or peripheral biomarkers of ADHD; articles that did not include a meta-analysis; and articles that did not present enough data for re-analysis. We excluded non-human studies, primary studies, genetic studies, and conference abstracts. We calculated the summary effect estimates (odds ratio [OR], relative risk [RR], and weighted mean difference [WMD]), 95% CI, heterogeneity I2 statistic, 95% prediction interval, small study effects, and excess significance biases. We did analyses under credibility ceilings, and assessed the quality of the meta-analyses with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). This study is registered with PROSPERO, number CRD42019145032. Findings We identified 1839 articles, of which 35 were eligible for inclusion. These 35 articles yielded 63 meta-analyses encompassing 40 environmental risk factors and protective factors (median cases 16 850, median population 91 954) and 23 peripheral biomarkers (median cases 175, median control 187).

Autism spectrum disorder (ASD) substantially contributes to the burden of mental disorders. Improved awareness and changes in diagnostic criteria of ASD may have influenced the diagnostic rates of ASD. However, while data on trends in diagnostic rates in some individual countries have been published, updated estimates of diagnostic rate trends and ASD-related disability at the global level are lacking. Here, we used the Global Burden of Diseases, Injuries, and Risk Factors Study data to address this gap, focusing on changes in prevalence, incidence, and disability-adjusted life years (DALYs) of ASD across the world. From 1990 to 2019, overall age-standardized estimates remained stable globally. Both prevalence and DALYs increased in countries with high socio-demographic index (SDI). However, the age-standardized incidence decreased in some low SDI countries, indicating a need to improve awareness. The male/female ratio decreased between 1990 and 2019, possibly accounted for by increasing clinical attention to ASD in females. Our results suggest that ASD detection in low SDI countries is suboptimal, and that ASD prevention/treatment in countries with high SDI should be improved considering the increasing prevalence of the disorder. Additionally, growing attention is being paid to ASD diagnosis in females, who might have been left behind by ASD epidemiologic and clinical research previously. ASD burden estimates are underestimated as GBD does not account for mortality in ASD.

Elevated levels of circulating high-sensitivity C-reactive protein (hs-CRP) have been observed in depression, with the body mass index (BMI) being a major mediator of this association. However, the sex difference in the association between hs-CRP and depression remains unclear. This study aimed to investigate the sex difference in the association between hs-CRP and depression. Data from the 2016 Korea National Health and Nutritional Examination Survey were used for our study. High hs-CRP was defined as >3.0 mg/L, while depression was determined using a cut-off score of 10 in the Patient Health Questionnaire-9. The study population comprised 5,483 Korean adults. Men with high hs-CRP levels showed statistically higher prevalence of depression than those with low hs-CRP levels (8.90% vs. 3.65%, P < 0.0001). The high hs-CRP group was 1.86 times more likely to have depression after adjusting for BMI and other covariates in men (adjusted odds ratio: 1.86; 95% confidence interval: 1.07–3.25; P = 0.029). Meanwhile, no statistically significant association between hs-CRP and depression was found among women. Depression was considerably associated with hs-CRP only in men, indicating a biological difference between men and women that can independently modify the relationship between hs-CRP and depression.

The aims of this study were to design a mobile app that would record daily self-reported Korean version of the Center for Epidemiologic Studies Depression Scale-Revised (K-CESD-R) ratings in a “Yes” or “No” format, develop two different algorithms for converting mobile K-CESD-R scores in a binary format into scores in a 5-point response format, and determine which algorithm would be more appropriately applied to the newly developed app. Algorithm (A) was designed to improve the scoring system of the 2-week delayed retrospective recall-based original K-CESD-R scale, and algorithm (B) was designed to further refine the scoring of the 24-hour delayed prospective recall-based mobile K-CESD-R scale applied with algorithm (A). To calculate total mobile K-CESD-R scores, each algorithm applied certain cut-off criteria for a 5-point scale with different inter-point intervals, defined by the ratio of the total number of times that users responded “Yes” to each item to the number of days that users reported daily depressive symptom ratings during the 2-week study period. Twenty participants were asked to complete a K-CESD-R Mobile assessment daily for 2 weeks and an original K-CESD-R assessment delivered to their e-mail accounts at the end of the 2-week study period. There was a significant difference between original and mobile algorithm (B) scores but not between original and mobile algorithm (A) scores. Of the 20 participants, 4 scored at or above the cut-off criterion (≥13) on either the original K-CESD-R (n = 4) or the mobile K-CESD-R converted with algorithm (A) (n = 3) or algorithm (B) (n = 1). However, all participants were assessed as being below threshold for a diagnosis of a mental disorder during a clinician-administered diagnostic interview. Therefore, the K-CESD-R Mobile app using algorithm (B) could be a more potential candidate for a depression screening tool than the K-CESD-R Mobile app using algorithm (A).