A32 THE ROLE OF GUT MICROBIOTA AND TRACE AMINES IN A MURINE MODEL OF GENERALIZED ANXIETY DISORDER
Bibliographic record
Abstract
Anxiety disorders are the most prevalent psychiatric conditions within primary care, affecting up to 29% of people across their lifetime. Generalized Anxiety disorder (GAD) is frequently comorbid with major depressive disorder, resulting in greater functional impairment. Gut microbiota have been shown to modulate brain chemistry and function, possibly also playing a role in the genesis of anxiety. Bacteria can produce, or interact with the host metabolism of neuroactive substances, including classical neurotransmitters and trace amines, like octopamine, which despite found in trace concentrations in the mammalian brain, can significantly affect CNS function. Trace amines alter catecholamine release, reuptake and biosynthesis, and modulate dopamine and serotonin metabolism. We investigated whether microbiota from patients with GAD and an absence of immune activation can induce altered behaviour in gnotobiotic mice and whether this is accompanied by changes in trace amines levels. Germ-free NIH Swiss mice (n=34) were colonized with microbiota from either a GAD patient (n=17) with moderate anxiety, comorbid depression, and low serum and fecal octopamine, or an age and sex-matched healthy control (HC) (n=17). Immune activation/inflammation profiles of human donors was assessed from tissue and plasma cytokines, CRP and β-defensin-3 levels. Microbiota profiles were assessed via 16S rRNA based Illumina. Three weeks post-colonization, mouse behaviour was assessed by standard psychometric tests. Emotionality z-scores were calculated to provide a robust integrated behavioural assessment. Fecal b-defensin-3 was measured via ELISA. After sacrifice, brain BDNF and GDNF expression will be assessed by immunofluorescence, and gene expression by qPCR. There were no differences in fecal b-defensin levels between mice with GAD and HC microbiota. However, GAD mice exhibited greater anxiety and depressive-like behavior compared to HC mice in the digging, marble-burying, step-down and tail suspensions tests. Behavioural z-scoring across all six standard psychometric tests showed a significant increase in group emotionality score means of GAD-colonized mice compared to HC-colonized mice (p= 0.02; Figure 1). Our results suggest that GAD microbiota has the ability to induce anxiety and depressive-like behavior, by mechanisms independent of the immune system, likely by altered production of trace amines. This needs to be confirmed however by full metabolomics analysis of stool and tissues samples, which is currently underway. Figure 1 - Individual and Group Emotionality Scores of GAD- and HC-colonized mice. Behavioural z-scoring across all six standardized psychometric tests showed a significant increase in group emotionality score means of GAD-colonized mice compared to HC-colonized mice (p= 0.02) NIH
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 imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".