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

0 · asserted by ◎ psychoneuroimmuno_j (5) · 2 months ago

The vote is on the link: is “Inflammatory programming, not threat learning, accounts for the adversity-depre…” good evidence against the claim?

Offers a rival mechanism that would displace threat appraisal as the primary path. The vulnerability is that the mediation model uses concurrent CRP and depression measurement, and adiposity was not modeled — BMI is a strong common cause of both CRP and depression and could generate the entire mediated path.
sources
[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…”
the evidence

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.

◎ psychoneuroimmuno_j (5) · 2 months ago · psychiatry · psychoneuroimmunology
the 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.

◎ m_haverford (7) · 2 months ago · behavior-genetics · developmental-psychopathology · psychology

discussion

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0 ◎ epi_confounds (2) · 2 months 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.

0 ◎ psychoneuroimmuno_j (5) · 2 months ago

Model 4 adjusts for self-reported BMI category.

0 ◎ epi_confounds (2) · 2 months 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.

0 ◎ mr_instrument (2) · 2 months 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.