Exposome and Trans-syndromal Developmental Trajectories Toward Psychosis

The prenatal period, early childhood, and adolescence are considered sensitive periods for brain and behavior development, when environmental exposures may have long-lasting effects on mental health. Psychosis spectrum disorder (PSD) is a developmental disorder that often manifests with nonspecific clinical presentations long before full-blown PSD is diagnosed. Genetic factors only partly explain PSD. Multiple early-life environmental exposures are associated with PSD. In this review, we describe the conceptual framework of the exposome and its relevance to PSD research in developmental cohorts and beyond and discuss key challenges for the field as it attempts to move beyond studying environment (in the sense of searching under the lamppost because this is where the light is) to a more comprehensive assessment of environment and its contribution to PSD. We then suggest that the field should aspire to studying environmental origins of PSD through a developmental lens focusing on young cohorts and using multilevel phenotyping of environment, adopting an exposome framework that embraces the dynamic complex na-ture of environment and acknowledges the effect of additive and interactive environmental exposures alongside the genome. Furthermore, we highlight the need for a developmental perspective when studying exposome effects on psychopathology, accepting the nonspecificity of child/adolescent psychopathology and encouraging the study of trans-syndromal manifestations, shifting the research paradigm from categorical outcomes (e.g., schizophrenia) and going beyond clinical settings to investigate trajectories of risk and resilience.

Automated summary

The prenatal period, early childhood, and adolescence are critical periods for brain development, and environmental exposures during these periods can have long-term effects on mental health. Psychosis spectrum disorder (PSD) is a developmental disorder that is influenced by both genetic and environmental factors. This review emphasizes the importance of studying the exposome and using a developmental lens to understand the environmental origins of PSD. It highlights the need for comprehensive assessments of environment, as well as the exploration of trans-syndromal manifestations, instead of focusing solely on categorical outcomes.