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<p>Despite decades of effort, depression research has made limited progress in improving predictive models and treatment outcomes. Biomarker studies, in particular, have yielded few clinically translatable findings. This Review argues that such limitations stem not from a lack of research activity, but from fundamental conceptual issues in defining and measuring major depression, specifically its theoretical construct, diagnostic criteria, subtyping, measurement tools and staging frameworks. We highlight three major challenges: (1) the heterogeneity of depression measurement, (2) insufficient attention to longitudinal disease trajectories and (3) underrepresentation of lived-experience perspectives. Here, to advance precision psychiatry, we propose focusing on specific symptom domains (for example, anhedonia, cognitive impairment and insomnia), modeling trajectories across multiple timescales with dynamic symptom assessments and improved staging, and integrating patient-defined outcomes into research via a core outcome set. These strategies aim to resolve conceptual limitations and support the development of more targeted, person-centered approaches to understanding and treating depression.</p>

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Key challenges in advancing research on depression phenotyping

  • 期刊论文

  • 发表日期：

    2026年5月12日

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  • Jonathan Repple,
  • Astrid Chevance,
  • Eiko Fried,
  • Moritz Elsaesser,
  • Tim Hahn,
  • Henricus G. Ruhe,
  • Nils Opel,
  • Claudi L. Bockting,
  • Roger S. McIntyre,
  • Allan H. Young,
  • Paolo Fusar-Poli,
  • Elisabeth Schramm,
  • Jessica Schleider,
  • Christian Otte,
  • Alix Choppin,
  • Udo Dannlowski,
  • Brenda W.J.H. Penninx,
  • Andreas Reif

摘要

Despite decades of effort, depression research has made limited progress in improving predictive models and treatment outcomes. Biomarker studies, in particular, have yielded few clinically translatable findings. This Review argues that such limitations stem not from a lack of research activity, but from fundamental conceptual issues in defining and measuring major depression, specifically its theoretical construct, diagnostic criteria, subtyping, measurement tools and staging frameworks. We highlight three major challenges: (1) the heterogeneity of depression measurement, (2) insufficient attention to longitudinal disease trajectories and (3) underrepresentation of lived-experience perspectives. Here, to advance precision psychiatry, we propose focusing on specific symptom domains (for example, anhedonia, cognitive impairment and insomnia), modeling trajectories across multiple timescales with dynamic symptom assessments and improved staging, and integrating patient-defined outcomes into research via a core outcome set. These strategies aim to resolve conceptual limitations and support the development of more targeted, person-centered approaches to understanding and treating depression.