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← Phenome Registry

PH002 — Motivation / Drive

Capacity to initiate effort, pursue goals, and maintain goal-directed behaviour.

How readily a person starts effort, pursues goals, and stays engaged with what matters to them.

Therapeutic areas: TA001 ★TA003TA004TA007

Provenance: Core Version 1 ADHD registry phenome. Benchmarked against RDoC Positive Valence Systems (motivation, reward learning) and kept distinct from Behavioural Activation (PH010) and Reward Regulation (PH009). (origin: BRAIN)

Related phenomes: PH009 — Reward Regulation, PH010 — Behavioural Activation

External framework cross-references

RDoC domains

  • Positive Valence Systems — reward learning
  • Positive Valence Systems — motivation / effort

DSM / ICD context

  • Attention-deficit/hyperactivity disorder
  • Major depressive disorder — motivational symptoms

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

Dopaminergic and endocannabinoid motivation biology are review-supported; open-label tyrosine and dietary precursor evidence is mechanistic or adjunct — not definitive motivation-intervention efficacy.

Construct landmark papers

  • MacDonald et al. (2024) — Reviews dopamine signalling in motivation and goal-directed behaviour.
  • Aquili (2020) — Catecholaminergic neurotransmission framing for effort and drive biology.

Biology → phenome landmark papers

  • Fernstrom (2013) — Precursor transport and tyrosine availability upstream of catecholaminergic drive circuits.
  • Garani et al. (2021) — Endocannabinoid system modulation of motivation and stress-related behavioural states.

Nutrition → biology landmark papers

  • Wurtman et al. (2003) — Dietary tyrosine and precursor manipulation affects catecholamine synthesis biology.
  • Reimherr et al. (1987) — Open-label tyrosine supplementation in ADHD — early human adjunct evidence for drive/activation biology.

Connected mechanisms

BRS-X(ECS)

BRS-X(Hormones)

BRS1

BRS5