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.

Integration of brain structural information into prognostic and treatment formulation is key for achieving an all-encompassing biopsychosocial approach in psychiatry. Uncovering biological markers of specific mental illnesses, specific illness stages and of remission, may help further our understanding of the aetiology and precipitators of certain types of psychopathologies, identify central neurobiological processes as distinct from epiphenomena, validate boundaries of clinical groups, and potentially aid in predicting response to treatment. This book chapter reviewed the current structural neuroimaging evidence in three prominent mental illness domains: schizophrenia-spectrum, bipolar and depressive disorders. The large degree of overlap in abnormal neuropathology across the broad mental illness groups, which is no doubt partially due to within-group heterogeneity, makes the discovery of sets or networks of localized diagnosis-specific neural biomarkers unlikely. However, this is not to say that subtle distinctions in neural abnormalities do not exist, but rather challenges the usefulness of traditional diagnostic categories in the context of brain imaging being applied within a clinical staging model. A focus on identifying and characterising microscale circuits that are dysfunctional and which map onto symptomatology in a transdiagnostic manner, may have the greatest implications for clinical translation in the near future.