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← Phenome Registry

PH003 — Emotional Regulation

Capacity to modulate emotional responses and maintain affective stability.

How well emotional responses can be modulated so mood and reactivity stay within a workable range.

Therapeutic areas: TA001 ★TA002TA003TA004TA006

Provenance: Core Version 1 ADHD registry phenome. Benchmarked against RDoC Negative Valence and Arousal/Regulatory Systems; distinct from Apprehensive Worry (PH016), Stress Reactivity (PH015), and Social Engagement (PH018). (origin: BRAIN)

Related phenomes: PH015 — Stress Reactivity, PH016 — Apprehensive Worry / Perseverative Thought, PH018 — Social Engagement Capacity

External framework cross-references

RDoC domains

  • Negative Valence Systems — sustained affect / affective regulation
  • Arousal and Regulatory Systems — affective regulation

DSM / ICD context

  • Attention-deficit/hyperactivity disorder — emotional dysregulation
  • Major depressive disorder
  • Generalised anxiety disorder

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

Construct and inhibitory-balance biology are strong; registry nutrition layer draws on mood/anxiety intervention reviews — not direct emotional-regulation phenome trials.

Construct landmark papers

  • Oades et al. (2010) — Reviews dopamine and serotonin roles in motivation, affect, and ADHD-related emotional function.
  • Edden et al. (2012) — GABA deficits in ADHD cohorts — construct validation for excitation–inhibition and affective control.

Biology → phenome landmark papers

  • Fernstrom (2013) — Serotonergic precursor biology intersects affective modulation pathways.
  • Briguglio et al. (2018) — Dietary neurotransmitter biology review spanning mood and anxiety-relevant serotonergic context.

Nutrition → biology landmark papers

  • Kiecolt-Glaser et al. (2011) — Omega-3 lowered anxiety and inflammatory markers in stressed adults — upstream affective biology.
  • Jackson et al. (2021) — Saffron RCT reported mood improvements — adjacent human nutrition→affective biology support.

Connected mechanisms

BRS-X(ECS)

BRS-X(Hormones)

BRS1

BRS3

BRS5