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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.
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.
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.
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.
Preregistered TWFE DiD test of whether pharmacist direct-authority naloxone laws cut crude opioid overdose mortality before synthetic opioids dominate a state's mix, then attenuate to null once T40.4 accounts for at least half of opioid overdose deaths. On the pinned panel (601 state-years, 2008–2021), ATT before dominance is -0.632217 (CI -4.144376 to 2.879942); the Law×SyntheticDominant interaction is 0.231578; ATT when dominant is -0.400639. Locked success flag false is false (decision refute). Re-run from code/analyze.py.