Evidence map›Paper›PMID 41840434›Full record

ArticleBMC psychology2026

Study protocol: role of the blood-brain barrier in stress resilience: investigating new pathways towards Pharmacological augmentation of stress resilience (a PHASR-PP project study).

Frédérique Mwm Maas, Sebastian Hachenberg, Julian Mituniewicz, Birgit Kleim, Susann Schweiger, Kenneth Sl Yuen, Flurin Cathomas, Dorota Kobylińska, Oliver Tüscher, Raffael Kalisch

Registry-linked trialAbstract readClinical Trial Protocol
In one paragraph

Article in BMC psychology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06965868 (Role of the Blood-Brain Barrier in Stress Resilience), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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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.

NCT06965868 nanot yet recruitingnot on this map

Role of the Blood-Brain Barrier in Stress Resilience: Investigating New Pathways Towards Pharmacological Augmentation of Stress Resilience (a PHASR-PP Project Study)

TypeinterventionalSponsorLeibniz-Institut für Resilienzforschung (LIR) gGmbHRan2025 to 2027Enrolled122ConditionsStress Resilience, Blood-Brain Barrier Integrity, Mental HealthArmsMetformin, Placebo
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

10 authors.

Frédérique Mwm Maas *Leibniz Institute for Resilience Research (LIR), Mainz, Germany. frederique.maas@lir-mainz.de.
Sebastian Hachenberg *Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
Julian Mituniewicz *Department of Psychology, University of Warsaw, Warsaw, Poland.
Birgit KleimDepartment of Psychology, University of Zurich, Zurich, Switzerland.
Susann SchweigerLeibniz Institute for Resilience Research (LIR), Mainz, Germany.
Kenneth Sl YuenLeibniz Institute for Resilience Research (LIR), Mainz, Germany.
Flurin Cathomas *Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
Dorota Kobylińska *Department of Psychology, University of Warsaw, Warsaw, Poland.
Oliver Tüscher *Leibniz Institute for Resilience Research (LIR), Mainz, Germany.
Raffael Kalisch *Leibniz Institute for Resilience Research (LIR), Mainz, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPreclinical research indicates that the integrity of the blood-brain barrier (BBB) is an important resilience factor. Further, there is preclinical evidence suggesting that the mTOR pathway regulates BBB function and that pharmacological inhibition of this pathway may improve stress resilience.

methodsTranslating these results to the human, we aim to establish a prospective association between BBB integrity and stress resilience in stressor-exposed individuals at risk to develop stress-related mental health problems. Using an observational study design, we primarily exploit assumed natural inter-individual variation in BBB integrity, assessed with neuroimaging, which we attempt to relate to inter-individual variation in stress resilience. We hypothesize that better whole-brain BBB integrity predicts better stress resilience. As a further measure to maximize sensitivity, we attempt to enhance inter-individual variation in BBB integrity by administering the indirect mTOR pathway inhibitor metformin to half of the participants, using a randomized parallel-group placebo-controlled double-blind multi-centre experimental design. This experimental-interventional approach also allows us to ask whether metformin improves whole-brain BBB integrity and whether this in turn improves stress resilience, via mediation analysis. Such a finding would suggest a causal role for BBB integrity in stress resilience. In additional analyses, blood-based biomarkers and regional neuroimaging metrics are used as measures of BBB integrity, and the influence of socio-demographic, anamnestic, psycho-social, immunological, metabolic, and other neuroimaging variables on BBB function and stress resilience is also considered. DISCUSSION: The study may, for the first time, delineate a relationship between BBB function and stress resilience in humans and potentially implicate BBB integrity as a causal factor in resilience. Findings may inform the development of novel pharmacological strategies to improve BBB function and stress resilience, to be investigated in follow-up studies.

trial registrationRegistered under National Library of Medicine under the number NCT06965868 (https//clinicaltrials.gov/study/NCT06965868, initial registration date 04/24/2025, study start date 01/02/2026).

Indexed as

Blood-Brain BarrierMetforminResilience, PsychologicalStress, PsychologicalAdultDouble-Blind MethodFemaleHumansMagnetic Resonance ImagingMaleMulticenter Studies as TopicObservational Studies as TopicRandomized Controlled Trials as TopicTOR Serine-Threonine KinasesYoung AdultMetforminTOR Serine-Threonine KinasesAt-riskBBB integrityMetforminPlacebo-controlledProspectiveStress resilience

Identifiers

PMID41840434
PMCPMC13063912

What Socratic holds

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Registered trials

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 Socratic graph.