Ethics of early detection of disease risk factors: A scoping review.

BACKGROUND: Scientific and technological advancements in mapping and understanding the interrelated pathways through which biological and environmental exposures affect disease development create new possibilities for detecting disease risk factors. Early detection of such risk factors may help prevent disease onset or moderate the disease course, thereby decreasing associated disease burden, morbidity, and mortality. However, the ethical implications of screening for disease risk factors are unclear and the current literature provides a fragmented and case-by-case picture. METHODS: To identify key ethical considerations arising from the early detection of disease risk factors, we performed a systematic scoping review. The Scopus, Embase, and Philosopher's Index databases were searched for peer-reviewed, academic records, which were included if they were written in English or Dutch and concerned the ethics of (1) early detection of (2) disease risk factors for (3) disease caused by environmental factors or gene-environment interactions. All records were reviewed independently by at least two researchers. RESULTS: After screening 2034 titles and abstracts, and 112 full papers, 55 articles were included in the thematic synthesis of the results. We identified eight common ethical themes: (1) Reliability and uncertainty in early detection, (2) autonomy, (3) privacy, (4) beneficence and non-maleficence, (5) downstream burdens on others, (6) responsibility, (7) justice, and (8) medicalization and conceptual disruption. We identified several gaps in the literature, including a relative scarcity of research on ethical considerations associated with environmental preventive health interventions, a dearth of practical suggestions on how to address expressed concerns about overestimating health capacities, and a lack of insights into preventing undue attribution of health responsibility to individuals. CONCLUSIONS: The ethical concerns arising with the early detection of risk factors are often interrelated and complex. Comprehensive ethical analyses are needed that are better embedded in normative frameworks and also assess and weigh the expected benefits of early risk factor detection. Such research is necessary for developing and implementing responsible and fair preventive health policies.

Proteomic insights into mental health status: plasma markers in young adults.

Global emphasis on enhancing prevention and treatment strategies necessitates an increased understanding of the biological mechanisms of psychopathology. Plasma proteomics is a powerful tool that has been applied in the context of specific mental disorders for biomarker identification. The p-factor, also known as the "general psychopathology factor", is a concept in psychopathology suggesting that there is a common underlying factor that contributes to the development of various forms of mental disorders. It has been proposed that the p-factor can be used to understand the overall mental health status of an individual. Here, we aimed to discover plasma proteins associated with the p-factor in 775 young adults in the FinnTwin12 cohort. Using liquid chromatography-tandem mass spectrometry, 13 proteins with a significant connection with the p-factor were identified, 8 of which were linked to epidermal growth factor receptor (EGFR) signaling. This exploratory study provides new insight into biological alterations associated with mental health status in young adults.

Adopting a child perspective for exposome research on mental health and cognitive development - Conceptualisation and opportunities.

Mental disorders among children and adolescents pose a significant global challenge. The exposome framework covering the totality of internal, social and physical exposures over a lifetime provides opportunities to better understand the causes of and processes related to mental health, and cognitive functioning. The paper presents a conceptual framework on exposome, mental health, and cognitive development in children and adolescents, with potential mediating pathways, providing a possibility for interventions along the life course. The paper underscores the significance of adopting a child perspective to the exposome, acknowledging children's specific vulnerability, including differential exposures, susceptibility of effects and capacity to respond; their susceptibility during development and growth, highlighting neurodevelopmental processes from conception to young adulthood that are highly sensitive to external exposures. Further, critical periods when exposures may have significant effects on a child's development and future health are addressed. The paper stresses that children's behaviour, physiology, activity pattern and place for activities make them differently vulnerable to environmental pollutants, and calls for child-specific assessment methods, currently lacking within today's health frameworks. The importance of understanding the interplay between structure and agency is emphasized, where agency is guided by social structures and practices and vice-versa. An intersectional approach that acknowledges the interplay of social and physical exposures as well as a global and rural perspective on exposome is further pointed out. To advance the exposome field, interdisciplinary efforts that involve multiple scientific disciplines are crucial. By adopting a child perspective and incorporating an exposome approach, we can gain a comprehensive understanding of how exposures impact children's mental health and cognitive development leading to better outcomes.

Protective effect of restorative possibilities on cognitive function and mental health in children and adolescents: A scoping review including the role of physical activity.

Background The exposome approach can be a powerful tool for understanding the intertwining of social, physical, and internal influences that shape mental health and cognitive development throughout childhood. To distil conceptual models for subsequent analyses, the EU-funded project Early Environmental quality and Life-course mental health effects (Equal-Life) has conducted literature reviews on potential mediators linking the exposome to these outcomes. We report on a scoping review and a conceptual model of the role of restorative possibilities and physical activity. Methods Peer-reviewed studies published since the year 2000 in English, on the association between the exposome and mental health/cognition in children/adolescents, and quantitatively investigating restoration/restorative quality as a mediating variable were considered. Database searches were last updated in December 2022. We used an unstructured expert-driven approach to fill in gaps in the reviewed literature. Results Five records of three distinct studies were identified, indicating a scarcity of empirical evidence in this newly developing research area. Not only were these studies few in numbers, but also cross-sectional, lending only tentative support to the idea that perceived restorative quality of adolescent's living environment might mediate the association between greenspace and mental health. Physical activity emerged as a mediator leading to better psychological outcomes in restorative environments. We provide a critical discussion of potential caveats when investigating the restoration mechanism in children and propose a hierarchical model including restoration, physical activity, and relational dynamics between children and their environment, including social context, as well as restorative environments other than nature. Conclusions It is justified to further explore the role of restoration and physical activity as mediators in the association between early-life exposome and mental health/cognitive development. It is important to consider the child perspective and specific methodological caveats. Given the evolving conceptual definitions/operationalizations, Equal-Life will attempt to fill in a critical gap in the literature.

Health effects of railway-induced vibration combined with railway noise - A systematic review with exposure-effect curves.

BACKGROUND: The combined health impact of concurrent railway noise and railway vibration exposure is not yet well understood. OBJECTIVES: This systematic review gives an overview of epidemiological studies on health effects from railway vibration, aiming to quantify this association with exposure-effect curves. Moreover, the combined health effects of vibration and concurrent noise were investigated. METHODS: We converted the vibration metric to an equivalent noise level and calculated an overall noise level by energetically summing the equivalent and railway noise level. The combined health effect was determined by using published evidence-based exposure-effect formulas. RESULTS: Studies included in this systematic review predominately investigated annoyance and self-reported sleep disturbances; no studies on manifest diseases were identified. For the combined effects of vibration and noise on "total" annoyance, the results based on the pooled analysis of CargoVibes project are recommended as conservative approach. DISCUSSION: Converting railway vibration into equivalent noise levels in dB may offer a pragmatic approach to assess the combined health effects of railway noise and railway vibration exposure. Future studies should include cardiovascular and mental diseases in addition to vibration-induced annoyance and sleep disturbances. Furthermore, future studies should include in-depth investigations of the interaction between railway noise and railway vibration to allow for a more accurate assessment of the railway-induced burden of disease.

The Interaction between Circulating Cell-Free Mitochondrial DNA and Inflammatory Cytokines in Predicting Human Mental Health Issue Risk in Adolescents: An Explorative Study.

Adolescence is often a challenging time in which psychiatric issues have a strong connection to mental health disorders later in life. The early identification of the problems can reduce the burden of disease. To date, the effective identification of adolescents at risk of developing mental health problems remains understudied. Altogether, the interaction between circulating cell-free mtDNA (ccf-mtDNA) and inflammatory cytokines in adolescents is insufficiently understood regarding experienced mental health difficulties. Our study selected the participants based on the Strength and Difficulty Questionnaire (SDQ) score using the cut-off points of 3 and 18 for the low and the high score groups, respectively. The answers of the SDQ at the age of 12.2-15.7 years contributed to the investigation of (i) whether ccf-mtDNA units are associated with cytokines, and (ii) if an interaction model for predicting risk of mental health issues is observed. We discovered a sex-specific correlation between the screened markers associated with mental health problems in the low and high SDQ score groups among the male participants and in the low SDQ score group among the female participants. The mitochondrial MT-ND4 and MT-CO1 genes correlated significantly with interleukin-12p70 (IL-12p70) in males and with monocyte chemoattractant protein-1 (MCP-1) in females. Due to the nature of the explorative study, the studied markers alone did not indicate statistical significance for the prediction of mental health problems. Our analysis provided new insight into potential plasma-based biomarkers to predict mental health issues.

Perceived Occupational Noise Exposure and Depression in Young Finnish Adults.

We investigated the association between perceived occupational noise exposure and depressive symptoms in young Finnish adults and whether noise sensitivity moderates this association. This study was based on an ongoing longitudinal twin study. We included those who had been working daily (n = 521) or weekly (n = 245) during the past 12 months (mean age 22.4, SD 0.7, 53% female). We asked about occupational noise exposure at age 22 and assessed depressive symptoms using the General Behavior Inventory (GBI) at age 17 and 22. Noise sensitivity and covariates were used in linear regression models. Perceived daily occupational noise exposure was associated, as a statistically independent main effect with depressive symptoms at age 22 (beta 1.19; 95% CI 0.09, 2.29) among all, and separately for females (beta 2.22; 95% CI 0.34, 4.09) but not males (beta 0.22; 95% CI -1.08, 1.52). Noise sensitivity was independently associated with depressive symptoms among all (beta 1.35; 95% CI 0.54, 2.17), and separately for males (beta 1.96; 95% CI 0.68, 3.24) but not females (beta 1.05; 95 % CI -0.04, 2.13). Noise sensitivity was independent of perceived occupational noise exposure. Pre-existing depressive symptoms at age 17 were predictive of perceived occupational noise exposure, suggesting complex interactions of noise and depression.

A step towards harmonising human biomonitoring study setup on European level: Materials provided and lessons learnt in HBM4EU.

Internal exposure of the human body to potentially harmful chemical substances can be assessed by Human Biomonitoring (HBM). HBM can be used to generate conclusive data that may provide an overview of exposure levels in entire or specific population groups. This knowledge can promote the understanding of potential risks of the substances of interest or help monitoring the success of regulatory measures taken on the political level. Study planning and design are key elements of any epidemiologic study to generate reliable data. In the field of HBM, this has been done using differing approaches on various levels of population coverage so far. Comparison and combined usage of the resulting data would contribute to understanding exposure and its factors on a larger scale, however, the differences between studies make this a challenging and somewhat limited endeavour. This article presents templates for documents that are required to set up an HBM study, thus facilitating the generation of harmonised HBM data as a step towards standardisation of HBM in Europe. They are designed to be modular and adaptable to the specific needs of a single study while emphasising minimum requirements to ensure comparability. It further elaborates on the challenges encountered during the process of creating these documents during the runtime of the European Joint Programme HBM4EU in a multi-national expert team and draws up lessons learnt in the context of knowledge management.

Lifestyle differences between co-twins are associated with decreased similarity in their internal and external exposome profiles.

Whether differences in lifestyle between co-twins are reflected in differences in their internal or external exposome profiles remains largely underexplored. We therefore investigated whether within-pair differences in lifestyle were associated with within-pair differences in exposome profiles across four domains: the external exposome, proteome, metabolome and epigenetic age acceleration (EAA). For each domain, we assessed the similarity of co-twin profiles using Gaussian similarities in up to 257 young adult same-sex twin pairs (54% monozygotic). We additionally tested whether similarity in one domain translated into greater similarity in another. Results suggest that a lower degree of similarity in co-twins' exposome profiles was associated with greater differences in their behavior and substance use. The strongest association was identified between excessive drinking behavior and the external exposome. Overall, our study demonstrates how social behavior and especially substance use are connected to the internal and external exposomes, while controlling for familial confounders.

Noise Indicators Relating to Non-Auditory Health Effects in Children-A Systematic Literature Review.

A systematic literature review was conducted to investigate which objective noise indicators related to various noise sources (i.e., aircraft, road-traffic, and ambient noise) are the best predictors of non-auditory health-effects in children. These relationships are discussed via a conceptual framework, taking into account main parameters such as the type of noise source, the exposure locations and their environments, the type of noise indicators, the children's mediating factors, and the type of non-auditory health effects. In terms of the procedure, four literature databases were screened and data was extracted on study design, types of noise sources, assessment method, health-based outcomes and confounders, as well as their associations. The quality of the studies was also assessed. The inclusion criteria focused on both indoor and outdoor environments in educational buildings and dwellings, considering that children spend most of their time there. From the 3337 uniquely collected articles, 36 articles were included in this review based on the defined inclusion and exclusion criteria. From the included literature, it was seen that noise exposure, assessed by energetic indicators, has significant associations with non-auditory health effects: psychophysiological, cognitive development, mental health and sleep effects. Percentile and event-based indicators provided significant associations to cognitive performance tasks and well-being dimension aspects.

Branched-chain amino acids linked to depression in young adults.

Depression is a heterogeneous mental health problem affecting millions worldwide, but a majority of individuals with depression do not experience relief from initial treatments. Therefore, we need to improve our understanding of the biology of depression. Metabolomic approaches, especially untargeted ones, can suggest new hypotheses for further exploring biological mechanisms. Using the FinnTwin12 cohort, a longitudinal Finnish population-based twin cohort, with data collected in adolescence and young adulthood including 725 blood plasma samples, we investigated associations between depression and 11 low-molecular weight metabolites (amino acids and ketone bodies). In linear regression models with the metabolite (measured at age 22) as the dependent variable and depression ratings (measured at age 12, 14, 17, or 22 from multiple raters) as independent variables [adjusted first for age, sex, body mass index (BMI), and additional covariates (later)], we initially identified a significant negative association of valine with depression. Upon further analyses, valine remained significantly negatively associated with depression cross-sectionally and over time [meta-analysis beta = -13.86, 95% CI (-18.48 to -9.25)]. Analyses of the other branched-chain amino acids showed a significant negative association of leucine with depression [meta-analysis beta = -9.24, 95% CI (-14.53 to -3.95)], while no association was observed between isoleucine and depression [meta-analysis beta = -0.95, 95% CI (-6.00 to 4.11)]. These exploratory epidemiologic findings support further investigations into the role of branched-chain amino acids in depression.

Early environmental quality and life-course mental health effects: The Equal-Life project.

BACKGROUND: There is increasing evidence that a complex interplay of factors within environments in which children grows up, contributes to children's suboptimal mental health and cognitive development. The concept of the life-course exposome helps to study the impact of the physical and social environment, including social inequities, on cognitive development and mental health over time. METHODS: Equal-Life develops and tests combined exposures and their effects on children's mental health and cognitive development. Data from eight birth-cohorts and three school studies (N = 240.000) linked to exposure data, will provide insights and policy guidance into aspects of physical and social exposures hitherto untapped, at different scale levels and timeframes, while accounting for social inequities. Reasoning from the outcome point of view, relevant stakeholders participate in the formulation and validation of research questions, and in the formulation of environmental hazards. Exposure assessment combines GIS-based environmental indicators with omics approaches and new data sources, forming the early-life exposome. Statistical tools integrate data at different spatial and temporal granularity and combine exploratory machine learning models with hypothesis-driven causal modeling. CONCLUSIONS: Equal-Life contributes to the development and utilization of the exposome concept by (1) integrating the internal, physical and social exposomes, (2) studying a distinct set of life-course effects on a child's development and mental health (3) characterizing the child's environment at different developmental stages and in different activity spaces, (4) looking at supportive environments for child development, rather than merely pollutants, and (5) combining physical, social indicators with novel effect markers and using new data sources describing child activity patterns and environments.

Health Effects Related to Wind Turbine Sound: An Update.

Commissioned by the Swiss Federal Office for the Environment, an update of an earlier narrative review was prepared for the literature published between 2017 and mid-2020 about the effects of wind turbine sound on the health of local residents. Specific attention was hereby given to the health effects of low-frequency sound and infrasound. The Netherlands Institute for Public Health and the Environment and Mundonovo sound research collected the scientific literature on the effect of wind turbines on annoyance, sleep disturbance, cardiovascular disease, and metabolic effects, as well as mental and cognitive impacts. It also investigated what is known about annoyance from visual aspects of wind turbines and other non-acoustic factors, such as the local decision-making process. From the literature study, annoyance again came forward as the most important consequence of sound: the louder the sound (in dB) of wind turbines, the stronger the annoyance response was. The literature did not show that "low-frequency sound" (sound with a low pitch) results in extra annoyance on top of normal sound. Results of scientific research for other health effects are either not available or inconsistent, and we can conclude that a clear association with wind turbine related sound levels cannot be confirmed. There is evidence that long-term effects are related to the annoyance people experience. These results confirm earlier conclusions. There is increasing evidence that annoyance is lower when people can participate in the siting process. Worries of residents should be addressed in an early stage, by involving them in the process of planning and decision making.

Analysis of different preferences for the EU's regulatory options for endocrine disruptor identification criteria using argumentation theory.

What criteria are most suitable to identify endocrine disrupting substances (EDSs) for regulatory purposes in the EU? The results of the European Commission's public consultation, as part of the process to establish identification criteria for EDSs, show that different regulatory options are supported. Some respondents prefer an option including hazard characterization considerations, whereas others prefer an option that avoids these considerations and introduces several hazard-identification based weight-of-evidence categories. In this study, the argumentation underlying the different preferences for identification criteria are analyzed and compared using pragma-dialectical argumentation theory (PDAT). All responses of non-anonymous, national governments that submitted a response in English (n = 17) were included. Responses of other stakeholder organizations were included if a Google News search returned an opinionated presence in the media on the subject (n = 9). Five topical themes and 21 underlying issues were identified. The themes are 1) mechanistic understanding of EDSs, 2) regulatory considerations related to the identification of EDSs, 3) consistency with existing regulatory frameworks, and 4) evaluations of specific issues related to a category approach and 5) related to including potency. We argue that two overarching (implicit) 'advocacy coalitions' can be discerned, that adopted contrasting positions towards the identified themes and issues. Among these 'coalitions', there appears to be consensus about the necessity of having 'science-based' criteria, though different perspectives exist as to what the most accurate mechanistic understanding of EDSs entails. To move the discussion forward, we argue that a societal dialogue would be beneficial, where EDS science and regulation are discussed as interrelated themes.

Evidence Relating to Environmental Noise Exposure and Annoyance, Sleep Disturbance, Cardio-Vascular and Metabolic Health Outcomes in the Context of IGCB (N): A Scoping Review of New Evidence.

WHO published the Environmental Noise Guidelines for the European Region in 2018, based on seven systematic reviews including studies published between 2000 and 2014. Since then, new studies were published. At the request of the UK Department for Environment, Food and Rural Affairs (DEFRA), a review on annoyance, sleep disturbance, cardiovascular and metabolic effects in relation to environmental noise was prepared. The aim was to advise the Interdepartmental Group on Costs and Benefits Noise Subject Group (IGCB(N)) whether this new evidence warrants an update of their recommendations. Four databases for observational studies were screened and data were extracted on design, type and measurements of exposures and outcomes and confounders and their associations. The quality of the studies was indirectly assessed for cardiovascular and metabolic effects by only including studies with a case control or cohort design. For studies on annoyance and sleep disturbance, the risk of bias was expressed in exposure misclassification, selective participation and confounding. The update yielded 87 papers, pertaining to 108 new studies of which 40 new studies were on annoyance, 42 on sleep disturbance and 26 concerning cardiovascular and metabolic effects. The number, size and quality of the new studies suggest new meta-analyses could be undertaken over the sources and effects included in the WHO reviews.

"Symptoms associated with environmental factors" (SAEF) - Towards a paradigm shift regarding "idiopathic environmental intolerance" and related phenomena.

Health conditions characterized by symptoms associated with chemical, physical and biological environmental factors unrelated to objectifiable pathophysiological mechanisms are often labelled by the general term "idiopathic environmental intolerances". More specific, exposure-related terms are also used, e.g. "multiple chemical sensitivities", "electromagnetic hypersensitivity" and "candidiasis hypersensitivity". The prevalence of the conditions varies from a few up to more than 50%, depending on definitions and populations. Based on evolving knowledge within this field, we provide arguments for a paradigm shift from terms focusing on exposure and intolerance/(hyper-)sensitivity towards a term more in line with the perceptual elements that seem to underlie these phenomena. Symptoms caused by established pathophysiologic mechanisms should not be included, e.g. allergic or toxicological conditions, lactose intolerance or infections. We discuss different alternatives for a new term/concept and end up proposing an open and descriptive term, "symptoms associated with environmental factors" (SAEF), including a definition. "Symptoms associated with environmental factors" both is in line with the current knowledge and acknowledge the experiences of the afflicted persons. Thus, the proposed concept is likely to facilitate therapy and communication between health professionals and afflicted persons, and to provide a base for better understanding of such phenomena in healthcare, society and science.