575-P: Serum Soluble Epoxide Hydrolase-Related Oxylipins Are Associated with Depression and Increased Symptom Severity in T2DM
Bibliographic record
Abstract
Depression in T2DM is associated with inflammation (e.g., interleukin-6 [IL-6]), but specific inflammatory pathways, and depressive symptoms involved, have not been identified. Cytochrome P450s (CYP450s) convert dietary fatty acids into pro-resolving epoxides but soluble epoxide hydrolase (sEH) metabolizes these into inactive diols, thereby limiting their anti-inflammatory benefits. We hypothesized that sEH oxylipins (diols and epoxides) will be associated with depression and increased symptom severity in T2DM. Patients with T2DM were diagnosed with depression (Structured Clinical Interview, DSM-5) and matched 1:1 to non-depressed patients for sex, HbA1c and BMI. Fasting serum oxylipins were quantified by ultra-high-performance liquid chromatography tandem mass spectrometry. All analyses controlled for IL-6, measured by ELISA. Diol/epoxide ratios were calculated to estimate sEH pathway flux. Among 20 depressed and 20 non-depressed patients (mean age 58.9±8.5, mean HbA1c 7.0±0.9%, 65% women), the 17,18 sEH derived eicosapentaenoic acid (EPA) diol was higher in depressed participants (F(1,37)=5.753, p=0.022). Somatic, negative affective, and anhedonic symptoms were screened (Center for Epidemiological Studies-Depression Scale). Three diol/epoxide oxylipin ratios were associated with higher somatic symptoms in the depressed group: the 16,17 docosahexaenoic acid (DHA) derived ratio (β=0.489, p=0.007), and both linoleic acid derived ratios (9,10 [β=0.549, p=0.017] and 12,13 [β=0.547, p=0.003]). The 14,15 arachidonic acid derived ratio was associated with higher negative affective symptoms (β=0.559, p=0.006). These associations were not found in non-depressed T2DM. This increased flux of omega-3 and omega-6 fatty acids through the sEH pathway associated with depression and symptom severity suggests the potential role of sEH inhibitors for T2DM-related depressive symptoms. Disclosure N. Z. Anita: None. P. Oh: None. B. R. Shah: None. J. Gilbert: Speaker’s Bureau; Self; Abbott Diabetes, Amgen Canada, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Dexcom, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi. A. Assal: None. W. Swardfager: None. N. Forkan: None. R. Kamal: None. M. M. Nguyen: None. D. Yu: None. C. Major-orfao: None. S. K. Wong: None. K. L. Lanctôt: None. N. Herrmann: None. Funding Canadian Institutes of Health Research; Banting & Best Diabetes Centre; National Institute of Diabetes and Digestive and Kidney Diseases
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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 | 0.000 | 0.001 |
| 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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 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".