Chronic psychosocial stress (CPS) is associated with adverse brain and mental health outcomes. Effects on the cerebral microvasculature have been proposed as an underlying mechanism, although this remains to be established. Here, we examined the association between CPS and an early marker of microvascular dysfunction, magnetic resonance imaging (MRI)-visible perivascular spaces (PVS). Analyses were conducted in two cohorts of healthy young adults (N = 61; ages 18-43 years; 88% male) using high-resolution 3T MRI and an automated PVS quantification pipeline. CPS was assessed using the Perceived Stress Scale (PSS-10). We applied a two-step meta-analytic framework and controlled for known allostatic factors impacting PVS, including age, body mass index and mean arterial pressure. In accordance with our hypothesis, individuals with higher CPS had significantly higher fractional PVS volumes in the centrum semiovale (CSO), in particular in the frontal and occipital lobes (pFDR < .05). No such effect was found in the basal ganglia, or in the CSO subdivision, parietal, and temporal lobes (pFDR > .09). Our findings indicate that CPS may contribute to subtle, centrum semiovale specific microvascular alterations even in healthy young adults. Future multimodal research including inflammatory marker and blood-brain barrier measures may help to elucidate mechanistic pathways.

MW is a member of the following advisory boards and gave presentations to the following companies: Boehringer Ingelheim, Germany; and Biologische Heilmittel Heel GmbH, Germany. MW has further conducted studies with institutional research support from Biologische Heilmittel Heel GmbH and Janssen Pharmaceutical Research unrelated to this investigation. VE is a member of the advisory board of Biologische Heilmittel Heel GmbH, Germany. LH is currently employed by Biologische Heilmittel Heel GmbH. All companies had no role in the design, conduct, or reporting of this study. All other authors report no biomedical financial interests or other potential conflicts of interest.

The present work was supported by: for LC Interdisciplinary Center of Clinical Research of the Medical Faculty Jena (AMS-21), Federal Ministry for Research, Technology and Aeronautics through German Center for Mental Health (01EE2507F); for MW Eberhard Karls University Tuebingen Fortune Projekt (nr. 2394-0-0), BMFTR (16SV8590), BMFTR through DZPG (01EE2305A/01EE2305F; 01EE2505A/01EE2505F; 01EE2507F). Computational PVS quantification was supported by The Galen and Hilary Weston Foundation under the Novel Biomarkers 2019 scheme (ref UB190097) administered by the Weston Brain Institute and the Row Fogo Centre for Research into Ageing and the Brain (AD.ROW4.35. BRO-D.FID3668413). It is also funded by UK Dementia Research Institute funded by UKDRI Ltd which received its funding from the UK Medical Research Council, Alzheimer Society and Alzheimer's Research UK (DRIEdi17/18, UKDRI-4002 UKDRI-4205). Funding sources had no role in the study design, data collection, analysis, and interpretation, the writing of the report, and the decision to submit the article for publication. Open Access funding enabled and organized by Project DEAL. We acknowledge support by the German Research Foundation Projekt-Nr. 512648189 and the Open Access Publication Fund of the Thueringer Universitaets- und Landesbibliothek Jena.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Study 1 was approved by the Ethical committee of Jena University Hospital (2022-2718-1-BO). Study 2 was approved by the Ethical committee of Medical Faculty of Eberhard Karls University Tuebingen (578/2016B01). All participants gave written informed consent and were reimbursed for their participation.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors.