Effect of depression and serotonin reuptake inhibitors antidepressant treatment during pregnancy on protein expression in the human placenta: A quantitative proteomics analysis
Bibliographic record
Abstract
Depression is one of the most prevalent mental health disorders affecting pregnant individuals, and serotonin reuptake inhibitors (SRIs) are the most prescribed medications to treat depressive symptoms during pregnancy. Both depression and SRI exposure may have developmental impacts, and as randomizing exposures and non-treatment is not feasible in humans, distinguishing the effect of each factor often remains challenging. To date, much of what guides clinical practice stems from reports of pregnant individuals and fetal/infant outcomes, overlooking the significant role of the placenta in maintaining a healthy pregnancy and mother-fetal health. In this study, we explored the effect of depression and SRI antidepressant treatment during pregnancy on the placental proteome. A shotgun proteomics method with liquid chromatography and tandem mass spectrometry (LC-MS/MS) was performed. A cohort of pregnant individuals (n = 82) was recruited in their 2nd trimester, and clinician-rated mood symptoms measured using the Hamilton Depression Rating Scale (HAM-D) were obtained from them during pregnancy to identify three exposure groups: non-depressed; depressed/non-SRI-treated; depressed/SRI-treated. Differential protein expression and over-representation analyses on the placentas of the group with depression/non-SRI compared with placentas from healthy individuals showed an increase in antioxidant enzymes and various senescence-associated secretory phenotypes (SASP) as well as a decrease in histone proteins. Such protein expression patterns are potentially indicative of placental senescence. Our findings reveal that depression not treated with SRIs is associated with the upregulation of proteins involved in platelet activation, degranulation, coagulation cascade, and amyloid fiber formation in the placenta. In contrast, when comparing placentas from the depressed group treated with SRIs to those with depressive symptoms without SRI treatment, we observed a downregulation of proteins related to senescence, amyloid fiber formation, and platelet activation in the SRI-treated group. This study suggests that treatment with SRIs may prevent the placental alterations observed in antenatal depression, such as placental senescence, platelet activation, and amyloid fiber formation, and, ultimately, pregnancy and fetal outcomes. Further studies are needed to confirm these findings.
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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 | 0.000 |
| 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 | 0.000 |
| 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 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".