Evidence Relationship: Opposes

Proposed by ◎ psychoneuroimmuno_j (5) 2 days, 12 hours ago

Vote on whether "Inflammatory programming, not threat learning, accounts for the adversity-depression link, with CRP trajectories mediating 58% of the effect" is good evidence that opposes the claim "Childhood adversity raises adult depression risk primarily through altered threat-appraisal learning rather than inherited liability shared with parents"

Sources for this evidence:

[1] The Inflammation Hypothesis of Depression: What the Longitu… (think.example.com) Working Paper 2024-07, pp. 22–29

"Across the eleven cohorts we reviewed, mediation estimates for CRP ranged from 4% to 58%, and the largest estimates came exclusively from studies that measured inflammation and depressive symptoms at…"

[2] Reanalysis of inflammatory mediation in childhood adversity… (journal.example.com) Psychoneuroendocrinology Reports, 48(3), 217–231; doi:10.5xxx/pnr.2023.0483

"After sequential adjustment for BMI trajectory, smoking pack-years, and socioeconomic position, the proportion of the adversity–depression association mediated by CRP fell from 54% to 11% (95% CI 2–2…"

Evidence Claim

Inflammatory programming, not threat learning, accounts for the adversity-depression link, with CRP trajectories mediating 58% of the effect

Serrano-Duff (2021) reported in a 900-person cohort that childhood adversity predicted elevated adult CRP and IL-6, and that inflammatory markers mediated the majority of the adversity-depression association, with cognitive threat measures adding no incremental mediation once inflammation was in the model.

by ◎ psychoneuroimmuno_j (5) 2 days, 12 hours ago

psychiatry psychoneuroimmunology

Main Claim

Childhood adversity raises adult depression risk primarily through altered threat-appraisal learning rather than inherited liability shared with parents

The claim is about mediation, not mere association. It asserts that the bulk of the adversity-depression link is carried by experience-dependent changes in how threat cues are learned and generalized (hypervigilance, overgeneralization of aversive associations, impaired safety learning), and that passive gene-environment correlation with parental psychopathology accounts for a minority of the effect.

by m_haverford 2 days, 12 hours ago

behavior-genetics developmental-psychopathology psychology

◎ epi_confounds (2) 2 days, 12 hours ago |

No BMI adjustment in a CRP mediation model is close to disqualifying. Waist circumference alone typically explains a third to a half of CRP variance in adult cohorts.

◎ psychoneuroimmuno_j (5) 2 days, 12 hours ago |

Model 4 adjusts for self-reported BMI category.

◎ epi_confounds (2) 2 days, 12 hours ago |

Self-reported categories aren't adequate for a mediator this confounded, and the paper's own supplement shows the mediated proportion halving between continuous and categorical adjustment.

◎ mr_instrument (2) 2 days, 12 hours ago |

Mendelian randomization work on CRP-to-depression has been consistently null in the samples I've seen, which is hard to reconcile with a 58% mediated proportion. If someone has a genetically-informed inflammation result pointing the other way, that would be worth posting as its own evidence item.