[P4–566]: ASSESSING THE IMPACT OF INFLAMMATION ON LIMBIC CIRCUITRY AND ITS ROLE IN DEPRESSION IN OLDER ADULTS
Bibliographic record
Abstract
Inflammation is hypothesized to represent an important biological event increasing the likelihood of major depressive episodes. Yet, the impact of inflammation on the limbic system involved in major depressive disorders remains to be determined. In this study, we examined how inflammation measured in older adults was related with a life history of major depression and the integrity of limbic circuitry. A total of 29 markers of inflammation were collected with lumbar punction (LP) of cerebrospinal fluid (CSF) in 68 older adults of the PREVENT-AD cohort of cognitively normal adults with a parental or multiple-sibling history of AD dementia. Resting state functional connectivity (rsfMRI) was collected within one month after the LP was performed. Participants provided history of depression and burnout at enrollment and subsequent visits. K-means clustering was applied to generate 3 groups of individuals based on their expressions of the 29 markers (low, intermediate and high levels of inflammation; fig 1.A). The rsfMRI analyses were restricted to correlation of the BOLD signal between 9 regions of interest located in bilateral amygdala, nucleus accumbens, anterior hippocampus, posterior hippocampus, and one in the periaqueductal grey (PAG). The strength of the functional connectivity between these ROIs was linearly correlated with the patients’ clusters using robust regressions. The frequency of major episode of depression or burnout was lower in individuals with low inflammation compared to intermediate and high levels of inflammation (χ > 4.4; ps < 0.037; fig 1.B). Functional connectivity between the left amygdala and the PAG was related with the amount of inflammation after correcting for multiple comparisons (F(2,63) = 5.24; p = 0.002; fig 1.C): post-hoc comparisons indicated that individuals with low inflammation showed higher connectivity than those with intermediate (p = 0.027) or high (p = 0.007) levels of inflammation. In older adults, levels of inflammation were associated with a history of major episode of depression or burnout and with altered functional connectivity between the amygdala and the PAG. These findings are in line with the proposition that inflammation may alter functions of the emotion brain and therefore represent a risk factor for depression. Four typical examples of marker of inflammation with respect to clustering performed on all 29 markers. B. The frequency of major episodes of major depression or burnout was related to levels of inflammation. C. Individuals with low levels of inflammation showed higher functional connectivity between the left amygdala and the PAG compared to individuals with intermediate or high levels of inflammation.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.006 | 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".