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Record W4401121466 · doi:10.1101/2024.07.29.605502

Pervasive neurovascular dysfunction in the ventromedial prefrontal cortex of female depressed suicides with a history of childhood abuse

2024· preprint· en· W4401121466 on OpenAlexaff
Marina Wakid, Daniel Manzoni de Almeida, Ryan Denniston, Anjali Chawla, Zahia Aouabed, Maria Antonietta Davoli, Kristin Ellerbeck, Reza Rahimian, Volodymyr Yerko, Elena Leonova-Erko, Gustavo Turecki, Naguib Mechawar

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldMedicine
TopicBirth, Development, and Health
Canadian institutionsMcGill UniversityDouglas Mental Health University Institute
Fundersnot available
KeywordsNeurovascular bundleVentromedial prefrontal cortexNeurosciencePrefrontal cortexHuman brainMedicinePsychologyPathologyCognition

Abstract

fetched live from OpenAlex

Abstract Exposure to early life adversity (ELA) poses a significant global public health concern, with profound pathophysiological implications for affected individuals. Studies suggest that ELA contributes to endothelial dysfunction, bringing into question the functional integrity of the neurovascular unit in brain regions vulnerable to chronic stress. Despite the importance of the neurovasculature in maintaining normal brain physiology, human neurovascular cells remain poorly characterized, particularly with regard to their contributory role in ELA-associated pathophysiologies. In this study, we present the first comprehensive transcriptomic analysis of intact microvessels isolated from postmortem ventromedial prefrontal cortex samples from adult healthy controls (CTRL) and matched depressed suicides with histories of ELA. Our findings point to substantive differences between men and women, with the latter exhibiting widespread gene expression changes at the neurovascular unit, including the key vascular nodal regulators KLF2 and KLF4 , alongside a broad downregulation of immune-related pathways. These results suggest that the neurovascular unit plays a larger role in the neurobiological consequences of ELA in human females.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.214
Teacher spread0.200 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2024
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicBirth, Development, and HealthFrench-language works237,207