Across Barriers: Blood–Brain and Gut Barrier Signaling in Psychiatric Disorders
Bibliographic record
Abstract
Psychiatric disorders affect millions of people worldwide. Despite widespread use of conventional treatments targeting monoaminergic systems, remission rates remain low, and many individuals experience treatment resistance or relapse. Consequently, there has been growing interest in the involvement of other systems, with exacerbated immune responses and barrier alterations reported in clinical settings and preclinical models. Indeed, emerging evidence supports disruption of the blood-brain barrier (BBB) and intestinal barrier in the etiology and progression of psychiatric conditions, notably major depression, bipolar disorder, and generalized anxiety. The BBB is a highly selective structure whose integrity is maintained by endothelial cells, astrocytes, pericytes, and cellular adhesion molecules. Loss of BBB integrity has been increasingly recognized not only as a marker of psychiatric disorders but also as a contributing factor in their development. The BBB and intestinal barrier share anatomical features and functions, especially with the gut-vascular barrier, which remains understudied. Intestinal barrier dysfunction is a hallmark of inflammatory bowel disease (IBD), a condition with a high rate of comorbidity with psychiatric disorders. Both barriers are characterized by similar cellular components and signaling pathways regulating permeability. Psychological stress, a major risk factor for psychiatric conditions and IBD, renders the BBB and intestinal barrier hyperpermeable, feeding a vicious cycle of exacerbated inflammation and ultimately, mood changes as discussed here. We highlight key signaling pathways linked to barrier development and function, including Wnt/β-catenin, VEGF, and FGF-2, and argue that they may contribute to the pathophysiology of mental disorders and IBD, and could be targeted to develop innovative diagnostic tools and treatments. Key limitations and knowledge gaps are reviewed. To sum up, barrier-related alterations have long been reported in clinical studies in psychiatry and are now receiving increasing attention at the mechanistic level, as they may be relevant to uncovering new therapeutic targets beyond traditional monoamine-focused treatments.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".