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The search for replicable markers — biological, psycho­ logical, social or their combinations — for psychiatric ill­ nesses carries on. In psychosis, attention has been directed to at­risk and first­episode populations, given the possibility that following markers in young people will avoid the con­ founds of chronicity and exposure to pharmacological treat­ ments. A variety of promising biomarkers have been evalu­ ated, but few have passed through the rigorous screens of broader replication and demonstrated clinical utility. 1,2 We argue in this editorial that such difficulties are unsur­ prising, given the construction of current studies and the fact that such disorders typically develop in adolescence and young adulthood. This “critical period” 3 for risk and onset of major youth mental illnesses, such as psychosis, coincides with deeply interlaced neurobiological, clinical, affective and cognitive development, not to mention profound changes in social interactions and exposures. We explore the implica­ tions of this backdrop, including how it should inform both the search for biomarkers and the design of future studies. Critical periods, neurobiology and mental health Adolescence to early adulthood, the age range when the early course of psychotic illness is most likely to emerge, is a win­ dow in which much is dynamic. At a neurobiological level, this includes neurons and synapses, neurotransmission, tro­ phic factors and long­term potentiation, among other phe­ nomena. 4 However, it is also a period of sexual maturation, exposure to novel social and physical environments, different forms of stress, new models and contexts for learning, and de­ veloping cognitive abilities, reasoning and affective states. 5

Dynamic endophenotypes and longitudinal trajectories: capturing changing aspects of development in early psychosis