Despite over a century of intensive research, no single biological marker has successfully translated into daily clinical practice. A key challenge in psychiatric research is that traditional diagnostic categories represent phenomenological constructs that do not necessarily circumscribe a biological homogenous entity, but encompass a whole range of disorders presenting with similar phenotypes. The clinical staging model shifts our focus to search for markers relevant to particular stages of mental disorders and provides a useful framework to differentiate overlapping and heterogeneous syndromes. The identification of such “stage” dependant markers may be more meaningful and of greater prognostic and therapeutic value than our quest for categorical disease markers. In this chapter, bioactive and inflammatory markers in emerging psychotic disorders are discussed. Their specific role in brain development, psychiatric disorder onset and management are reviewed. Implications for future research are also provided.

For over a decade a transdiagnostic clinical staging framework for youth with anxiety, mood and psychotic disorders (linked with measurement of multidimensional outcomes), has been utilised in over 8,000 young people presenting to the enhanced primary (headspace) and secondary care clinics of the Brain and Mind Centre of the University of Sydney. This framework has been evaluated alongside a broad range of other clinical, neurobiological, neuropsychological, brain imaging, circadian, metabolic, longitudinal cohort and controlled intervention studies. This has led to specific tests of its concurrent, discriminant and predictive validity. These extensive data provide strong preliminary evidence that: i) varying stages of illness are associated with predicted differences in a range of independent and objectively measured neuropsychological and other biomarkers (both cross-sectionally and longitudinally); and, ii) that earlier stages of illness progress at variable rates to later and more severe or persistent disorders. Importantly, approximately 15-20% of those young people classed as stage 1b or ‘attenuated’ syndromes at presentation progress to more severe or persistent disorders. Consequently, this cohort should be the focus of active secondary prevention trials. In clinical practice, we are moving to combine the staging framework with likely pathophysiological paths (e.g. neurodevelopmental-psychotic, anxiety-depression, circadian-bipolar) to underpin enhanced treatment selection.