Abstract

Abstract In the question put forward by Scott et al., implications about the role of immune activation in depressive or other mood disorders were suggested. Low-level inflammation, triggered by the release of inflammatory molecules such as cytokines, has been detected in individuals with major mood disorders. These markers can be present in very low concentrations, posing a significant analytical challenge and complicating their use as reliable biomarkers. In this Perspective, we discuss the potential promise in leveraging nanotechnology and trace-level analysis of biomarkers of immune activation to enhance our molecular understanding of the immune system’s functioning and its association with depressive and other mood disorders. This Perspective critically discusses the analytical challenges of trace biomarker detection, highlighting issues with variability in study methodologies and cohort heterogeneity and emphasising the need for diurnal and longitudinal sampling to study circadian disruption and immune activation. Profiling inflammatory markers in this manner could create individualised molecular fingerprints, revealing disruptions in immune synchronisation with circadian rhythms and detecting abnormalities linked to specific mood disorder subtypes, and particularly ‘circadian depression’. As the profiling of general inflammatory markers may not be sufficient to study any causative relationship between immune activation and major mood disorders, we propose the exploration of novel biomarkers such as extracellular vesicles to support these investigations. The use of nanotechnologies for trace profiling of diurnal variations of inflammatory molecules, in combination with novel biomarkers, offers a promising strategy to develop a molecular understanding of the role of immune activation in depressive and other mood disorders.

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