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← Phenome Registry

PH015 — Stress Reactivity

Intensity and pattern of physiological and affective responses to stressors.

How strongly and quickly the system reacts to stress — distinct from longer-term stress resilience.

Therapeutic areas: TA001 ★TA002TA004TA006

Provenance: Core Version 1 registry phenome for stress-response intensity. Distinct from Stress Resilience (PH006) per RF002 — reactivity (acute response) versus adaptive buffering. (origin: BRAIN)

Related phenomes: PH006 — Stress Resilience, PH003 — Emotional Regulation

External framework cross-references

RDoC domains

  • Negative Valence Systems — acute threat / fear
  • Arousal and Regulatory Systems — stress response

DSM / ICD context

  • Generalised anxiety disorder
  • Attention-deficit/hyperactivity disorder — emotional reactivity

Foundational Evidence

Registry-level Phenome Evidence Confidence (below) is independent of Biology → Phenome Relationship Strength and Evidence Confidence on individual mechanism pages. Use the scoring guide for definitions of all three scores.

These are three independent scores. They are not combined or averaged. A phenome can have Medium registry evidence while individual mechanism rows show different relationship strength and evidence scores.

1. Phenome Evidence Confidence (Phenome Registry only)

Question: How convincing is the foundational evidence that this phenome is a valid, well-defined functional construct — and that diet-relevant biology can plausibly connect to it?

Not a roll-up of Biology → Phenome Relationship Strength or Evidence Confidence from Primary Mechanism page rows. Those are scored per mechanism; this score is assigned once per phenome at registry level.

Derived from foundational landmark evidence organised in up to three layers: construct validation, biology→phenome linkage, and nutrition→biology modulation. Each layer may include one or many landmark papers depending on registry review.

2. Biology → Phenome Relationship Strength (Primary Mechanism phenome rows)

Question: If this PM/FM biology were substantially impaired in isolation, how directly would that phenome be expected to suffer — within BRAIN architecture?

How it is derived: Reviewers read the PM/FM definition and biological function first — initially ignoring attached references and whether dietary intervention studies exist. References are reviewed only when scoring Evidence Confidence (below).

Score levels (the value shown on each row as Biology → Phenome Relationship Strength):

  • High — primary biological determinant (e.g. noradrenergic signalling → attention; GABA synthesis → calming tone)
  • Medium — major contributory determinant, not the sole driver
  • Low–Medium — established but indirect, modulatory, or one integrative step removed
  • Low — distal, conditional, or weak biological coupling

“Not dietary treatment efficacy” means this score does not ask whether a diet or supplement treats the phenome. It asks whether the biology itself is architecturally relevant. Limited dietary RCT evidence belongs in Evidence Confidence, not here.

3. Evidence Confidence (Primary Mechanism phenome rows)

Question: How convincing is the adjudicated evidence on that specific row that this biology actually relates to this phenome?

How it is derived: Assigned after Biology → Phenome Relationship Strength, by reviewing the relationship evidence on that PM/FM row. Judges whether the evidence supports the relationship — not just mechanism or phenome in isolation.

  • High — strong convergent human evidence directly linking mechanism biology to phenome variation
  • Medium — multiple human lines supporting the relationship; may include one bridge study with an inferential step
  • Low–Medium — convergent translational stack without direct mechanism↔phenome measurement on the row
  • Low — mechanistic or preclinical only; mechanism and phenome supported separately but not bridged

Often equal to or lower than Biology → Phenome Relationship Strength. Can occasionally be higher when outcome evidence is stronger than the mechanism's contributory role.

Phenome Evidence Confidence: Low–Medium

E/I balance and redox biology are review-supported; magnesium and homocysteine nutrition links are mechanistic — not stress-reactivity disorder intervention trials.

Construct landmark papers

  • Mamiya et al. (2021) — Excitation–inhibition balance framing for stress-related psychiatric phenotypes.
  • Clerc et al. (2013) — Magnesium and stress-axis physiology — construct validation for reactivity biology.

Biology → phenome landmark papers

Nutrition → biology landmark papers

Connected mechanisms

BRS6