Evidence map›Paper›PMID 41663714›Full record

ReviewMolecular psychiatry2026

The many-to-many problem of endophenotypes in psychiatry - a biological perspective.

Juergen Dukart, Leon D Lotter, Casey Paquola, Simon B Eickhoff, Leonhard Schilbach

Abstract readReview
In one paragraph

Review in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Juergen DukartInstitute of Neurosciences and Medicine, Brain & Behaviour (INM-7), Research Centre Juelich, Juelich, Germany. j.dukart@fz-juelich.de.ORCID http://orcid.org/0000-0003-0492-5644
Leon D LotterInstitute of Neurosciences and Medicine, Brain & Behaviour (INM-7), Research Centre Juelich, Juelich, Germany.ORCID http://orcid.org/0000-0002-2337-6073
Casey PaquolaInstitute of Neurosciences and Medicine, Brain & Behaviour (INM-7), Research Centre Juelich, Juelich, Germany.
Simon B EickhoffInstitute of Neurosciences and Medicine, Brain & Behaviour (INM-7), Research Centre Juelich, Juelich, Germany.
Leonhard SchilbachDepartment of General Psychiatry 2, LVR-Klinikum Duesseldorf, Bergische Landstraße 2, 40629, Duesseldorf, Germany.ORCID http://orcid.org/0000-0001-5547-8309

Funding

Deutsche Forschungsgemeinschaft (German Research Foundation) 549186835
6 · The paper itself

Abstract

While modern diagnostic classification systems aim to nosologically structure psychiatric disorders, they poorly align with the genetic, neurobiological, and environmental heterogeneity observed in these disorders. This limitation has complicated the search for clinically useful biomarkers for diagnosis and treatment. Recent work on genetic and environmental contributions to mental health indicates that this heterogeneity stems from differential involvement of diverse biological pathways within and across diagnostic clusters. This complex interplay presents a many-to-many mapping problem in psychiatry, where distinct pathophysiological processes can lead to similar clinical symptoms. Here, we argue that disentangling these biological mechanisms requires development of process-specific biomarkers that could replace non-specific neuroimaging markers widely used in neuropsychiatric research. We further propose a framework for biomarker research that adopts a biologically informed perspective integrating the interactions between genes and the environment to address this problem. Such a multidimensional framework holds promise for developing biology-driven models of psychiatric disorders, enabling treatment strategies tailored to individual pathophysiology.

Indexed as

EndophenotypesMental DisordersPsychiatryBiomarkersGene-Environment InteractionHumansBiomarkers

Identifiers

PMID41663714
PMCPMC13190287

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.