Beyond seeing only illness in abnormality: Clinical challenges and methodological promises on the road towards precision psychiatry

Mental disorders are highly prevalent and impose substantial burdens on individual well-being, daily functioning, and society; yet early diagnosis, risk identification, subtyping, and effective treatment remain major clinical challenges. Precision psychiatry has emerged to mitigate these challenges and aims to deliver “the right treatment to the right patient at the right time” . The translation of precision psychiatry into practice, however, is still limited. Here, we propose that progress towards precision psychiatry depends on addressing four interdependent and interdisciplinary challenges: moving from (i) diagnostic categories to transdiagnostic mechanisms, (ii) homogeneous groups to individual heterogeneity, (iii) only behavioral symptoms to complementary biological markers, and (iv) a cross-sectional to a longitudinal research focus. Importantly, these challenges are not independent, but can rather be organized as a cascading framework of interdependent components that together define the requirements for more personalized mental health care. For each level of this cascade, we review methodological promises and critically evaluate their strengths and limitations in relation to the conceptual framework. In doing so, we delineate why their clinical impact remains limited by identifying key methodological gaps that must be addressed to meet the requirements of the highest level of the cascade and to achieve fully personalized care. Finally, we synthesize all insights into a concrete proposal for moving forward, which calls for a conceptual shift from a diagnosis-centered perspective to a health-centered one, focused on individual mental health trajectories. Ultimately, implementing such individualized, health-centered approaches at the highest level of the cascade might make diagnosis and treatment more globally accessible, thereby improving the well-being of individuals across diverse populations and clinical settings.