Similar studies

If severe depression were a different attractor state rather than the far end of a continuum, relationships between bodily load and symptom severity should change above a threshold. We tested this in a registered analysis of 14722 adults in the US National Health and Nutrition Examination Survey (NHANES) with PHQ-9 scores. Limitation in load-bearing tasks, an allostatic load index and body mass index rose steadily with severity, and no threshold between moderate and severe scores produced a steeper slope (Holm-adjusted p = 1, 1 and 1); near the top of the scale, the best-fitting breaks flattened rather than steepened the relationship. Height, a negative control, showed no break. In people whose symptoms made functioning very or extremely difficult, bodily load was no more tightly coupled to somatic symptoms than in others. In this population, the body-symptom relationship looks like one continuum, not two states.

• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: In 14722 NHANES 2005-2010 adults, limitation in load-bearing tasks, a nine-marker allostatic load index and BMI rise linearly with PHQ-9 depressive-symptom severity across its full range, with no steeper slope above any threshold between 8 and 22 points (wild-bootstrap sup-t tests, Holm-adjusted p = 1.0, 1.0 and 1.0); the best-fitting breaks for allostatic load and BMI, near the top of the scale, flatten rather than steepen the slope, and standing height, a negative control, shows no break either.
• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: The partial association of load-bearing limitation with somatic depressive symptoms, adjusting for cognitive-affective symptoms, is no stronger in adults whose symptoms make functioning very or extremely difficult (partial Spearman 0.1607, n = 454) than in other adults with symptoms (0.1746; difference -0.0139, 95% CI -0.1036 to 0.0773).

Ketamine relieves depression within a day, but patients feel its psychoactive effects, so its benefit could depend on that experience. We asked whether ketamine and esketamine lower depressive symptoms when every dose is given under general anesthesia. Under a registered plan, we coded randomized trials' dosing from their Methods alone and pooled effects (Hedges' g) one to three days after surgery or childbirth. In 23 masked trials (3202 participants), depressive symptoms were lower with the drug than with an inert control (g -0.61, confidence interval -0.81 to -0.4; Holm-adjusted p < 0.001), though trials varied widely. Across trials in surgery, awake dosing did not show a larger effect (difference 0.12, -0.24 to 0.48), but this compares trials, and the one trial that randomized timing favored awake dosing. Masked doses also lowered pain. Ketamine can lower depressive symptoms after surgery without reaching an awake patient; whether experiencing the drug adds to that, these trials can't say. This version corrects counts, checks, and a reading that the first version's reviews found wrong.

• Published, Reproduced.Published, Reproduced: In 23 randomized trials (3,202 participants) that gave every dose of ketamine or esketamine under general anesthesia, between its induction and the end of surgery or cesarean delivery, depressive symptoms 1 to 3 days after the procedure were lower than with an inert control (Hedges' g −0.61, 95% CI −0.81 to −0.40; Holm-adjusted p < 0.001), though the trials varied widely (95% prediction interval −1.51 to 0.29). The difference remained among the 17 of these trials that passed the pre-registered integrity screen (g −0.48, −0.63 to −0.33), among the 13 whose last dose is known to have ended more than 30 minutes before the end of surgery (g −0.67, −1.04 to −0.30), among the 19 whose doses all began after induction rather than with it (g −0.60, −0.85 to −0.36), and with any single trial left out (largest p < 0.001).

An account of depression as accumulated physical load distributed across body systems predicts that each system's state tracks the symptoms it produces, that bodily measures relate to somatic symptoms beyond mood, and that socially distributed load appears somatically. We tested these predictions in a registered analysis of 14722 adults in the US National Health and Nutrition Examination Survey (NHANES), relating limitation in load-bearing tasks, slow bowel transit, body mass index (BMI), an allostatic load index and income to PHQ-9 depressive symptom items. Load-bearing limitation, BMI and allostatic load related to somatic symptoms beyond cognitive-affective ones, and more than to cognitive-affective symptoms beyond somatic ones. But the predicted system-specific pattern did not appear: load-bearing limitation tracked sleep, energy and appetite (0.2946) far more than slow transit did (0.0404). Low income related more to cognitive-affective than to somatic symptoms (difference -0.0996). Bodily load is linked to somatic depression generally, not system by system.

• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: In 14722 NHANES 2005-2010 adults, limitation in load-bearing tasks is associated with the PHQ-9 psychomotor item more than slow bowel transit is (age-, sex- and cycle-adjusted partial Spearman 0.2038 vs 0.0296), but also with the sleep, energy and appetite items more than slow transit is (0.2946 vs 0.0404; difference -0.2542, 95% CI -0.2762 to -0.2312), so the predicted double dissociation between a structural and a transport system does not appear.
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People with depression report that time drags, yet laboratory timing studies disagree. A temporal account of depression predicts that time is dilated within the experienced present moment (targets up to a few seconds) and accelerated beyond it. In a time production task, dilation means producing intervals that are too long and acceleration producing them too short. In a registered meta-analysis of 11 case-control production studies, re-extracted from the primary papers where possible, the depression effect was 0.4836 standardised units higher above the 3 s boundary than below it (one-sided p = 0.03380082115675086), with overproduction at short targets (g = -0.2851) and underproduction at longer ones (g = 0.1985), neither significant alone. The effect rose by 0.6302 per tenfold increase in duration. Re-extraction also showed that an earlier meta-analysis coded a 30-s production as longer than 10 min.

• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: Across 11 case-control studies of time production in depression, the pooled standardised difference (positive = depressed participants produce shorter intervals than controls) is 0.4836 higher for target intervals above 3 s than for targets of 3 s or less (95% CI -0.0431 to 1.0103; one-sided p = 0.034), with pooled g = -0.2851 at 3 s or less (3 studies; 95% CI -0.6917 to 0.1214) and g = 0.1985 above 3 s (10 studies; 95% CI -0.1378 to 0.5348).
• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed:

An observational atlas linked GLP-1 receptor agonists to dozens of outcomes beyond glucose, weight and the heart. We pooled the serious adverse events that 234 placebo-controlled trials, with 161309 participants, posted to ClinicalTrials.gov, coded blind to the results under a registered plan. Reports of serious bacterial infection (ratio 0.88, confidence interval 0.83 to 0.93) and pneumonia (0.87) were less frequent on the drugs, as were pneumonia counted in people and death. The reductions held under random effects, with any trial left out, if infection terms overlapped within participants as all serious events do in each comparison, and in trials not coded as recording only on treatment. Of the atlas's associations with enough events to test, the trials found three in its direction with no difference from it detected, contradicted none, and left most inconclusive, among them every neurological and psychiatric one; its large hazard of drug-induced pancreatitis concerns a subtype the trials don't separate.

• Published, Reproduced.Published, Reproduced: Of the 539 interventional studies of GLP-1 receptor agonists with results on ClinicalTrials.gov on 2026-10-12, 234 randomized trials compare a GLP-1 receptor agonist with placebo, in 257 comparisons with 161,309 participants in their adverse-event tables (93,765 on the drugs and 67,544 on placebo). In them, reports of serious gallbladder and biliary disease, counting a participant once for each of the outcome's terms they had, are more frequent on the drugs (Mantel-Haenszel ratio 1.38, 95% CI 1.21 to 1.57), and so are reports of serious nausea and vomiting (2.02, 1.52 to 2.68), as the trials' own publications and the drugs' labels lead one to expect.