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PH004 — Cognitive Energy Stability

Capacity to maintain mental energy and avoid cognitive energy crashes across the day.

How evenly mental energy holds up through the day without sharp crashes or fog.

Therapeutic areas: TA001 ★TA003TA005TA006TA007

Provenance: Core Version 1 registry phenome for mental energy stability across the day. Distinguished from Energy Stability Under Variable Conditions (PH012) and fuel-substrate phenome (PH013) as cognitive energy tone rather than metabolic supply mechanics. (origin: BRAIN)

Related phenomes: PH011 — Cognitive Clarity, PH012 — Energy Stability Under Variable Conditions, PH013 — Energy Stability Under Variable Fuel Conditions

External framework cross-references

RDoC domains

  • Arousal and Regulatory Systems — fatigue / energy regulation
  • Cognitive Systems — cognitive effort

DSM / ICD context

  • Major depressive disorder — fatigue
  • Long COVID — cognitive fatigue

Foundational Evidence

Registry-level Phenome Evidence Confidence (below) is independent of Biology → Phenome Confidence 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 Biology → Phenome 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 Confidence 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 Confidence (Primary Mechanism page §3 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 Confidence):

  • 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 page §3 rows)

Question: How convincing are the attached Key References on that specific row that this biology actually relates to this phenome?

How it is derived: Assigned after Biology → Phenome Confidence, by reviewing only the references on that PM/FM row. Judges whether refs support 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 Confidence. Can occasionally be higher when outcome evidence is stronger than the mechanism's contributory role.

Phenome Evidence Confidence: Low–Medium

Mitochondrial and metabolic-flexibility reviews anchor the construct; micronutrient and sex-hormone links are mechanistic — limited direct cognitive-fatigue outcome demonstration on the registry stack.

Construct landmark papers

  • Li et al. (2023) — Mitochondrial function and brain energy metabolism in neuropsychiatric contexts.
  • Goodpaster & Sparks (2017) — Metabolic flexibility review — substrate switching and energetic resilience framing.

Biology → phenome landmark papers

  • Depaoli et al. (2021) — Estrogen–insulin resistance biology intersects brain energy and mood regulation.
  • Pirinen et al. (2020) — NAD⁺/mitochondrial biology and human energy metabolism — bioenergetic phenome context.

Nutrition → biology landmark papers

  • Tardy et al. (2020) — B-vitamin supplementation and fatigue/energy outcomes — micronutrient→bioenergetic biology.
  • Pirinen et al. (2020) — Niacin/NAD precursor intervention modulates mitochondrial energetic capacity in humans.

Connected mechanisms

BRS-X(Hormones)

BRS4

BRS6