Associations between metabolic syndrome and anxiety, and the mediating role of inflammation: Findings from the UK Biobank.

OBJECTIVES: To investigate the association between metabolic syndrome (MetS) and anxiety and to explore the mediating role of inflammation indicators in this relationship based on the UK Biobank prospective cohort. METHODS: This population-based retrospective cohort study analyzed data from 308,352 participants. MetS was defined according to criteria jointly developed by the American Heart Association, the National Heart, Lung, and Blood Institute, and the International Diabetes Federation. Anxiety was defined using ICD-10 codes. Cox proportional risk regression models were used to explore the hazard ratios (HRs) between MetS, components of MetS, number of MetS components, and anxiety. The mediating effect of inflammation on the association between MetS and anxiety was explored using longitudinal mediation analysis. RESULTS: A total of 308,352 participants were included in this study. Of these, 9471 (3.071 %) developed anxiety over a mean follow-up of 12.05 years. In the fully adjusted model, MetS increased the risk of anxiety by 13.6 % (HR: 1.136, 95 %CI: 1.085-1.189). All MetS components significantly increased the risk of anxiety, with HRs ranging from 1.066 to 1.165. When MetS was treated as a linear variable, the risk of anxiety increased by 6.5 % per component increment. Age-stratified results showed that the risk of MetS for anxiety was higher among those <55 years (HR: 1.23, 95 %CI: 1.13-1.33) than among those ≥55 years (HR: 1.12, 95 %CI: 1.06-1.18). The mediating effects of platelets, lymphocytes, neutrophils, C-reactive protein, leukocytes, and INFLA scores on the association between MetS and anxiety were significant, with mediating effects of 2.30 %, 7.20 %, 15.9 %, 20.7 %, 22.0 %, and 25.3 %, respectively, and a combined mediating effect of these inflammatory factors was 30.8 % (except for INFLA scores). CONCLUSIONS: MetS and its components significantly increased the risk of anxiety, which increased with the number of components. This association may be partially mediated by serum inflammatory indicators, suggesting that MetS may increase the risk of anxiety by elevating the level of chronic inflammation.

Association between prenatal exposure to per- and polyfluoroalkyl substances and neurodevelopment in children: Evidence based on birth cohort.

BACKGROUND: Although numerous studies have examined the effect of prenatal per- and polyfluoroalkyl substances (PFAS) exposure on neurodevelopment in children, findings have been inconsistent. OBJECTIVE: To better understand the effects of PFAS exposure during pregnancy on offspring neurodevelopment, we conducted a systematic review of prenatal exposure to different types of PFAS and neurodevelopment in children. METHODS: A comprehensive search was conducted in the PubMed, Web of Science, and EMBASE electronic databases up to March 2023. Only birth cohort studies that report a specific association between PFAS exposure during pregnancy and neurodevelopment were included in this review. RESULTS: 31 birth cohort studies that met the inclusion criteria were qualitatively integrated. Among these, 14 studies investigated the impact of PFAS exposure during pregnancy on cognition, 13 on neurobehavior, and 4 on both cognition and neurobehavior. Additionally, 4 studies explored the influence of PFAS on children's comprehensive development. CONCLUSION: Prenatal PFAS exposure was associated with poor neurodevelopment in children, including psychomotor development, externalizing behavior, and comprehensive development. However, conclusive evidence regarding its effects on other neurological outcomes remains limited. In addition, sex-specific effects on social behavior and sleep problems were identified.

Association of the Oxidative Balance Score and Cognitive Function and the Mediating Role of Oxidative Stress: Evidence from the National Health and Nutrition Examination Survey (NHANES) 2011-2014.

BACKGROUND: Oxidative stress is possibly related to cognitive function decline. The oxidative balance score (OBS) that combines pro- and antioxidant components from diet and lifestyle has been reported to be associated with age-related diseases. OBJECTIVES: We aimed to investigate the association between OBS and cognitive function in older adults and explore whether oxidative stress mediated this relationship. METHODS: A total of 1745 adults aged ≥60 y were included in the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Cognitive function was measured using 4 tests: the immediate recall test, delayed recall test, animal fluency test (AFT), and digital symbol substitution test (DSST). Weighted multivariate linear regression and restricted cubic splines (RCS) analyses were used to evaluate the association between OBS and cognitive function, and mediation analysis was used to test the indirect effect of oxidative stress indicators on the association. RESULTS: The OBS was positively associated with AFT, DSST, and global cognitive function in older adults, and the beta estimates (95% CI) were 0.015 (0.008, 0.034), 0.009 (0.002, 0.025), and 0.030 (0.024, 0.074), moreover, RCS results suggested an approximately linear dose-response relationship between the OBS and these 3 tests. The highest quartiles of these 3 tests were also significantly correlated with OBS. Albumin, uric acid, and serum 25(OH)D concentrations were significant mediators of the relationship between OBS and cognitive function, and the overall mediation effect proportion was 36% when included in 1 model. CONCLUSIONS: OBS was positively correlated with cognitive function in older adults, and albumin, uric acid, and serum 25(OH)D concentrations could be the driving mediators of the association. The findings emphasize the importance of a healthy, antioxidant diet and lifestyle that contribute to cognitive function. J Nutr 20xx;x:xx.

Oxidative balance scores and depressive symptoms: Mediating effects of oxidative stress and inflammatory factors.

BACKGROUND: Few studies have examined the combined effects of dietary and lifestyle factors on depressive symptoms. This study aimed to evaluate the association between oxidative balance score (OBS) and depressive symptoms and the underlying mechanisms. METHODS: A total of 21,283 adults from the 2007 to 2018 National Health and Nutrition Examination Survey (NHANES) were included. Depressive symptoms were defined as a total score of ≥10 on the Patient's Health Questionnaire (PHQ-9). Twenty dietary and lifestyle factors were selected to calculate the OBS. Multivariable logistic regression analyses were used to evaluate the association between OBS and depression risk. Mediation analyses were conducted to explore the roles of oxidative stress and inflammatory markers. RESULTS: In multivariate model, a significant negative association was found between OBS and depression risk. Compared with those in OBS tertile 1, participants in tertile 3 had lower odds of developing depressive symptoms (OR:0.50; 95 % CI:0.40-0.62; P < 0.001). Restricted cubic splines showed a linear relationship between OBS and depression risk (P for nonlinearity = 0.67). Moreover, higher OBS was found to be associated with lower depression scores (ß = -0.07; 95 % CI:-0.08, -0.05; P < 0.001). GGT concentrations and WBC counts mediated the association between OBS and depression scores by 5.72 % and 5.42 %, respectively (both P < 0.001), with a joint mediated effect of 10.77 % (P < 0.001). LIMITATIONS: This study was a cross-sectional design making it difficult to infer a causal association. CONCLUSIONS: OBS is negatively associated with depression, which may be mediated in part by oxidative stress and inflammation.

Association of urinary heavy metals co-exposure and adult depression: Modification of physical activity.

OBJECTIVE: This study aimed to evaluate the association between urinary heavy metal mixture exposure and depression, and the modifying role of physical activity in the effects of heavy metal mixture on depression risk was also considered. METHODS: Data of this study were derived from the National Health and Nutrition Examination Survey 2011-2016. Depression was measured by the Patient Health Questionnaire. We first selected 6 (cadmium, cobalt, tin, antimony, thallium, and mercury) from 14 heavy metals through elastic net regression for further analysis. Then binomial logistic regression, generalized additive model, environment risk score (ERS), and weighted quantile sum (WQS) regression were adopted to assess the effects of six metals individual and cumulative exposure on depression risk. Finally, we also examined whether physical activity could mitigate the effects of heavy metal co-exposure on depression risk. RESULTS: Totally, 4212 participants were included and 7.40% of subjects were with depression. We found urinary tin and antimony were separately associated with increased odds of depression (Sb: OR = 1.285, 95% CI: 1.064-1.553; Sn: OR = 1.281, 95% CI: 1.097-1.495), and a linear dose-response relationship between tin and depression was also noticed (P < 0.05). Meanwhile, urinary heavy metals co-exposure was positively related to depression risk (ERSQ4: OR = 2.691, 95% CI: 1.399-5.174; WQSpositive: OR = 1.465, 95% CI: 1.063-2.021), in which tin, antimony, and cadmium were identified with greater contributions to the overall mixture effect. In both ERS and WQS models, the significant positive association between the metal mixture and depression risk remained only in those who were inactive in physical activity. CONCLUSION: Our study concluded the detrimental effect of heavy metals in combined exposure on the risk of depression, which might be attenuated by physical activity.

Association between pyrethroid exposure and risk of depressive symptoms in the general US adults.

This study aimed to investigate the association between pyrethroid exposure and the risk of depressive symptoms in adults in the USA. Data of participants aged ≥20 years (n = 6455) from the National Health and Nutrition Examination Survey (NHANES, 2007-2014) were included. 3-Phenoxybenzoic acid (3-PBA), an adequately detected pyrethroid metabolite, was used as a biomarker to assess pyrethroid exposure. Depressive symptoms were defined as the Patient's Health Questionnaire (PHQ-9) total score ≥10 or use of antidepressant. Multivariable logistic regression analyses were performed to examine the association between urinary 3-PBA levels and the risk of depressive symptoms. In this study, 1150 participants (weighted frequency, 18.45%) developed depressive symptoms. Participants in the highest tertile have a higher risk of depressive symptoms than those in the lowest tertile of urinary 3-PBA and weighted OR of 1.28 (95% CI, 1.00-1.63, P=0.019). There was a nonlinear association between urinary 3-PBA and depressive symptoms (P for nonlinearity = 0.034). Mediation analysis showed the mediating effect of trouble sleeping on the association of urinary 3-PBA with depressive symptoms was 28.8% (P = 0.006). Our findings indicate that pyrethroid exposure is associated with the increased risk of depressive symptoms, and trouble sleeping may mediated this association. Further studies should be conducted to validate our findings and elucidate their underlying mechanisms.

Associations between urinary caffeine and caffeine metabolites and cognitive function in older adults.

BACKGROUND: The effects of caffeine on cognitive impairment have not been conclusively determined. This study aimed to objectively assess the correlation between the urinary caffeine and caffeine metabolites and cognitive decline in older adults. METHODS: Data on urinary caffeine and caffeine metabolites and the cognitive performance of participants aged 60 years and older were extracted from the National Health and Nutrition Examination Surveys 2011-2014. Binary logistic regression and restricted cubic splines (RCS) analyses were used to evaluate the association between urinary caffeine and caffeine metabolites and cognitive performance. RESULTS: Eight hundred twenty-seven individuals were enrolled in this cross-sectional study. We observed that 1-methylxanthine, 3-methylxanthine, 7-methylxanthine, 1,3-dimethylxanthine, 1,7-dimethylxanthine, and 3,7-dimethylxanthine levels were significantly and inversely associated with cognitive decline. The RCS results suggested an approximately linear dose-response relationship between the aforementioned metabolites and cognitive performance. Moreover, the effects of urinary caffeine and caffeine metabolites on cognitive function assessed using the AFT were more evident in men. CONCLUSIONS: Our study suggested that urinary caffeine and caffeine metabolite levels were associated with a reduced risk of cognitive impairment in a linear manner, especially in men.