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← Phenome Registry

PH008 — Sleep / Calming Tone

Capacity to downshift arousal and support sleep-compatible physiological regulation.

How readily arousal can downshift toward calmer, sleep-compatible physiological states.

Therapeutic areas: TA001 ★TA002TA004TA006

Provenance: Core Version 1 registry phenome for arousal downshift and sleep-compatible regulation. Benchmarked against RDoC Arousal/Regulatory Systems (sleep–wake, circadian). (origin: BRAIN)

Related phenomes: PH003 — Emotional Regulation, PH015 — Stress Reactivity

External framework cross-references

RDoC domains

  • Arousal and Regulatory Systems — sleep–wake regulation
  • Arousal and Regulatory Systems — circadian rhythms

DSM / ICD context

  • Insomnia disorder
  • ADHD — sleep disturbance

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

GABAergic sleep biochemistry is mechanistically strong (Cataldo); human dietary sleep-outcome evidence on the registry stack is limited — not sleep-disorder treatment efficacy.

Construct landmark papers

  • Cataldo et al. (2024) — Comprehensive review of PLP-dependent GABA synthesis and sleep-relevant inhibitory neurochemistry.
  • Fernstrom (2013) — Precursor biology intersecting serotonergic sleep–wake and calming tone pathways.

Biology → phenome landmark papers

Nutrition → biology landmark papers

  • Bravo et al. (2011) — Gut–brain GABAergic modulation via microbiota — dietary probiotic context for calming biology.
  • Clerc et al. (2013) — Magnesium and neuromuscular/sleep-related physiology — nutritional calming-tone modulator.

Connected mechanisms

BRS1

BRS6