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Understanding the Exposome

The Internal Domain of the Exposome​

Internal exposome is a consequence of external exposome filtered by personal vulnerabilities and lifestyle. It is measured in the person and can include biomarkers (i.e., indicators of exposure, susceptibility or outcome) but can also include processes that happen in the body and that can be analysed as a whole (e.g. metabolism, hormones, gut microflora, inflammation). Biomarkers are biological indicators measurable, e.g. in saliva, hair, blood or urine. A well-known example is the hormone cortisol as a marker of stress. 

What is a biomarker?​

Biomarkers are widely defined as any substance, structure, or process that can be measured in the body or its products and influence or predict the incidence of outcome or disease (World Health Organization, 2001). A biomarker is a molecule or other factors inside the body that indicates a normal or abnormal process, condition or disease. A known biomarker for depressive disorders, for instance, are cytokines, which are inflammatory markers that are associated with the biological response to stress-related exposures in depression (Goldsmith et al, 2016; Dudek et al., 2019). The term “biomarker” is neutral in the sense that it can be an indicator for both beneficial and harmful effects.

 

So, biomarkers are specific biological components that can reflect a specific trait, condition, or disease. Biomarkers can be used for: 

  • understanding the biological basis of mental health and psychopathology;

 revealing the mechanisms to strengthen the assessment of a causal relationship

  • early warning and detection, identifying individuals with a higher risk of developing or an early stage of a disease. This also increases the odds for cost-effective intervention at an early stage.

  • monitoring progression, tackling the longitudinal trajectory of the investigated process;

  • personalised medicine, promoting detailed stratification of the individual with risk, implementing the most appropriate treatment, and adjusting dosage in time.

How are the biomarkers determined in Equal-Life?

We have used three different approaches and two cohorts to identify biomarkers in blood plasma: proteomics, metabolomics and mitochondrial DNA. For proteome and metabolome, both untargeted and targeted analyses have been performed. Untargeted analysis refers to the comprehensive approach to simultaneously identify thousands of markers without a prior knowledge of specific targets. On the contrary, targeted analyses measure specific predefined targets of interest. Thus, untargeted analyses can identify novel biomarker candidates that can then be further examined in targeted analyses.

Which biomarkers of mental health were identified in Equal-Life?

Protein biomarkers

Protein biomarkers were examined in several studies using blood plasma samples from the FinnTwin12 and WALNUTs cohorts. Overall, we identified 111 proteins significantly linked to the self-reported symptoms of both internalising (like anxiety and depression) and externalising (like aggression) domains. Our subsequent analysis using bioinformatics tools revealed that these proteins are involved in immune responses and brain development processes. These results show that behavioural symptoms of mental unwell-being have a reflection in the biological level, although the causality and the direction of these associations remain unknown.
Additionally, we utilised a European-wide database covering Finland, the UK, and Estonia to further validate what we found. This validation confirmed that the genes responsible for 30 proteins are strongly associated with neurological, psychotic, or psychological traits. Thus, we found candidate protein biomarkers indicating the underlying biological processes involved in youth mental health and early psychopathology.

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Metabolite biomarkers

Similarly, metabolite biomarkers were examined in several studies using blood plasma samples from the FinnTwin12 and WALNUTs cohorts. We identified both cohort-specific and shared, functionally similar metabolites involved in energy metabolism, lipid transportation and multiple brain functions. The strongest evidence of metabolomic alterations linked to the mental health outcomes in adolescents and young adults was found for energy metabolism. These results mean that future research and interventions should specifically target energy metabolism and lipids

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Mitochondrial DNA biomarkers

We used plasma samples from the WALNUTs cohort to investigate the association between mitochondrial DNA and behavioural symptoms. In our analyses, no significant associations were found. This means that mitochondrial DNA does not show the potential of being used as early biomarkers of youth mental health.

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