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Evidence-based Knowledge Synthesis and Hypothesis Validation: Navigating Biomedical Knowledge Bases via Explainable AI and Agentic Systems
Published on: June 13, 2025
Need for evidence-based early intervention programmes: a public health perspective
Sinan Guloksuz1,2, Jim van Os1,3,4
1Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands.
Abstract:
This paper attempts to discuss why the early intervention agenda based on the current convention of 'ultra-high risk' (UHR) or 'clinical high risk' (CHR) for 'transition' to psychosis framework has been destined to fall short of generating a measurable and economically feasible public health impact. To summarise: (1) the primary determinant of the 'transition' rate is not the predictive value of the UHR/CHR but the degree of the risk-enrichment; (2) even with a significant pre-test risk enrichment, the prognostic accuracy of the assessment tools in help-seeking population is mediocre, failing to meet the bare minimum thresholds; (3) therapeutic interventions arguably prolong the time-to-onset of psychotic symptoms instead of preventing 'transition', given that the UHR/CHR and 'transition' lie on the same unidimensional scale of positive psychotic symptoms; (4) meta-analytical evidence confirms that specific effective treatment for preventing 'transition' (the goal-primary outcome-of the UHR/CHR framework) is not available; (5) the UHR/CHR-'transition' is a precarious target for research given the unpredictability driven by the sampling strategies and the natural ebb and flow of psychotic symptoms within and between individuals, leading to false positives; (6) only a negligible portion of those who develop psychosis benefits from UHR/CHR services (see prevention paradox); (7) limited data on the cost-effectiveness of these services exist. Given the pitfalls of the narrow focus of the UHR/CHR framework, a broader prevention strategy embracing pluripotency of early psychopathology seems to serve as a better alternative. Nevertheless, there is a need for economic evaluation of these extended transdiagnostic early intervention programmes.
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