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Phenome Register — human experiences and functional states across cognitive, emotional, social, lifestyle, health, physical performance, and mental wellbeing domains

Phenome Registry

The BRAIN Phenome Knowledge Database intentionally applies a narrower operational definition of "phenome" than is used in the wider phenomics literature. Although phenomes may include physiological and metabolic characteristics, the purpose of this registry is to catalogue human functional outcomes that are meaningful within cognitive, behavioural and mental health contexts. Biological capacities such as ATP production, fuel switching, mitochondrial substrate flexibility, or adaptive/allostatic metabolic resilience remain important, but are represented as emergent properties of coordinated Biological Regulatory Systems performance rather than as standalone phenomes.

The registry is scoped to neuropsychiatric and neurocognitive health. ADHD (TA001) is the primary worked example in Version 1; the architecture supports anxiety, depression, autism spectrum, cognitive ageing, long COVID, and healthy cognitive optimisation without duplicating phenome labels per condition.

Mechanism-to-phenome links are translational relationships. They do not imply that a single mechanism causes or treats a complex condition.

Phenome development

Candidate phenomes were developed within the BRAIN Framework as functional outcome domains linking biological regulatory systems to clinically relevant cognitive, behavioural, emotional, social, and physiological capacities. During development, the registry was compared with established research frameworks, including the NIH Research Domain Criteria (RDoC), to identify omissions, reduce overlap between phenomes, and improve construct separation. These external frameworks were used to validate and refine the taxonomy rather than define its structure. The BRAIN Phenome Registry therefore represents an independent translational classification informed by, but not derived from, existing neuropsychiatric research frameworks.

  • NIH Research Domain Criteria (benchmark) — Used to identify omissions, reduce phenome overlap, and improve construct separation — not the defining taxonomy.
  • WHO International Classification of Functioning, Disability and Health (benchmark) — Optional cross-reference for activity and participation domains where clinically relevant.

Therapeutic areas

IDTherapeutic areaDescription
TA001ADHD — primary V1 exampleAttention-deficit/hyperactivity disorder and related executive-function, impulsivity, and hyperactivity phenotypes.
TA002Anxiety DisordersGeneralised anxiety, social anxiety, panic, and related hyperarousal and worry phenotypes.
TA003Depressive DisordersMajor depression, dysthymia, and related motivational, affective, and cognitive slowing phenotypes.
TA004Autism SpectrumAutism spectrum conditions and related sensory, social-cognitive, and regulatory phenotypes.
TA005Cognitive AgeingAge-related cognitive decline, mild cognitive impairment, and dementia-risk cognitive phenotypes.
TA006Long COVIDPost-acute infection syndromes with cognitive, fatigue, and autonomic phenotypes.
TA007Healthy Cognitive OptimisationNon-clinical cognitive performance, resilience, and brain-health optimisation contexts.

Registry overview

Showing 15 of 15 phenomes
IDPhenomeDescriptionTherapeutic areasPhenome Evidence ConfidenceConnected Mechanisms
PH001Focus / Attention StabilityCapacity to sustain, shift, and regulate attention across changing cognitive demands.TA001 ★TA002TA004TA005TA006TA007Low–Medium
21 mechanisms
BRS-X(Hormones-PM1) — Oestrogen Signalling Stabilityindirect · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS1-FM1-PM1 — Amino-Acid Availability & Prioritisationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS1-FM1-PM2 — LAT1 Competitive Transport Modulationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS1-FM1-PM3 — Dopaminergic Signalling Regulationmodulates · Relationship Strength: High · Evidence: Medium
BRS1-FM1-PM4 — Noradrenergic Signallingmodulates · Relationship Strength: High · Evidence: Low–Medium
BRS1-FM2-PM6 — Acetylcholine Synthesis Supportmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS1-FM3-PM7 — Neuronal Membrane DHA Incorporationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS1-FM4-PM10 — Glutamate Clearance & Recyclingmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS2-FM1-PM1 — Folate/B12-Dependent Homocysteine Remethylationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS2-FM1-PM2 — Betaine/BHMT Remethylationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS2-FM1-PM4 — Methionine Cycle Fluxmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS2-FM3-PM7 — Phosphatidylcholine Formationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM1-PM1 — NF-kB Signalling Regulationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM1-PM2 — Gut-Derived Inflammatory Signallingmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM2-PM3 — Nrf2-Mediated Cellular Defence Regulationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM2-PM4 — ROS Generation vs Clearance Balancemodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM2-PM5 — Lipid Peroxidation Controlmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM3-PM7 — Cytokine Network Modulationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM3-PM8 — Eicosanoid / SPM Balancemodulates · Relationship Strength: Low · Evidence: Low
BRS4-FM1-PM1 — Electron Transport Chain Functionmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS4-FM3-PM6 — Carnitine-Mediated Fat Transportmodulates · Relationship Strength: Medium · Evidence: Medium
PH002Motivation / DriveCapacity to initiate effort, pursue goals, and maintain goal-directed behaviour.TA001 ★TA003TA004TA007Low–Medium
8 mechanisms
BRS-X(ECS-PM1) — NAPE → NAE Biosynthesis Capacitysupports · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS-X(ECS-PM4) — Endocannabinoid–Dopamine Neuromodulationsupports · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS-X(Hormones-PM5) — Testosterone Signalling Stabilitysupports · Relationship Strength: Medium · Evidence: Medium
BRS-X(Hormones-PM6) — Androgen-Microbiome Regulationindirect · Relationship Strength: Low · Evidence: Low
BRS1-FM1-PM1 — Amino-Acid Availability & Prioritisationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS1-FM1-PM2 — LAT1 Competitive Transport Modulationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS1-FM1-PM3 — Dopaminergic Signalling Regulationmodulates · Relationship Strength: High · Evidence: Medium
BRS1-FM1-PM4 — Noradrenergic Signallingmodulates · Relationship Strength: Medium · Evidence: Low–Medium
PH003Emotional RegulationCapacity to modulate emotional responses and maintain affective stability.TA001 ★TA002TA003TA004TA006Low–Medium
22 mechanisms
BRS-X(ECS-PM1) — NAPE → NAE Biosynthesis Capacitymodulates · Relationship Strength: Low · Evidence: Low
BRS-X(ECS-PM2) — Omega-3-Derived Endocannabinoidome Signallingmodulates · Relationship Strength: Low · Evidence: Low
BRS-X(ECS-PM3) — FAAH-Mediated Endocannabinoid Preservationmodulates · Relationship Strength: Low · Evidence: Low
BRS-X(ECS-PM5) — Endocannabinoid Stress-Buffering Capacitymodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS-X(Hormones-PM1) — Oestrogen Signalling Stabilitymodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS-X(Hormones-PM2) — Estrobolome Regulationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS-X(Hormones-PM3) — Progesterone-Supportive Microbial Metabolismmodulates · Relationship Strength: Low · Evidence: Low
BRS-X(Hormones-PM4) — Metabolic-Reproductive Hormone Integrationindirect · Relationship Strength: Low · Evidence: Low
BRS-X(Hormones-PM5) — Testosterone Signalling Stabilitymodulates · Relationship Strength: Low · Evidence: Low
BRS-X(Hormones-PM6) — Androgen-Microbiome Regulationindirect · Relationship Strength: Low · Evidence: Low
BRS1-FM1-PM1 — Amino-Acid Availability & Prioritisationmodulates · Relationship Strength: Low · Evidence: Low
BRS1-FM1-PM2 — LAT1 Competitive Transport Modulationmodulates · Relationship Strength: Low · Evidence: Low
BRS1-FM1-PM5 — Serotonergic Signalling Regulationsupports · Relationship Strength: High · Evidence: Low–Medium
BRS1-FM3-PM7 — Neuronal Membrane DHA Incorporationmodulates · Relationship Strength: Medium · Evidence: Medium
BRS1-FM4-PM9 — GABA Synthesis Capacitymodulates · Relationship Strength: Medium · Evidence: Medium
BRS2-FM1-PM3 — SAMe Synthesisindirect · Relationship Strength: Low–Medium · Evidence: Low
BRS3-FM1-PM1 — NF-kB Signalling Regulationmodulates · Relationship Strength: Low · Evidence: Low–Medium
BRS3-FM1-PM2 — Gut-Derived Inflammatory Signallingmodulates · Relationship Strength: Low · Evidence: Low
BRS3-FM2-PM4 — ROS Generation vs Clearance Balancemodulates · Relationship Strength: Low · Evidence: Low–Medium
BRS3-FM2-PM5 — Lipid Peroxidation Controlmodulates · Relationship Strength: Low · Evidence: Low
BRS3-FM2-PM6 — Antioxidant Network Recyclingmodulates · Relationship Strength: Low · Evidence: Low–Medium
BRS3-FM3-PM8 — Eicosanoid / SPM Balancemodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
PH004Cognitive Energy StabilityCapacity to maintain mental energy and avoid cognitive energy crashes across the day.TA001 ★TA003TA005TA006TA007Low–Medium
10 mechanisms
BRS-X(Hormones-PM4) — Metabolic-Reproductive Hormone Integrationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS-X(Hormones-PM5) — Testosterone Signalling Stabilitymodulates · Relationship Strength: Low–Medium · Evidence: Medium
BRS-X(Hormones-PM6) — Androgen-Microbiome Regulationindirect · Relationship Strength: Low · Evidence: Low
BRS1-FM1-PM3 — Dopaminergic Signalling Regulationindirect · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS4-FM1-PM1 — Electron Transport Chain Functionmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS4-FM1-PM2 — NAD⁺ Metabolismmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS4-FM1-PM3 — Creatine–Phosphocreatine Energy Bufferingmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS4-FM3-PM6 — Carnitine-Mediated Fat Transportmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS4-FM3-PM7 — Ketone Utilisation Capacityindirect · Relationship Strength: Low · Evidence: Low
BRS4-FM3-PM8 — Metabolic Fuel Switchingindirect · Relationship Strength: Low–Medium · Evidence: Low
PH005Recovery CapacityCapacity to restore function after cognitive, emotional, metabolic, or physical load.TA001 ★TA005TA006TA007Low–Medium
9 mechanisms
BRS-X(ECS-PM5) — Endocannabinoid Stress-Buffering Capacitymodulates · Relationship Strength: Low · Evidence: Low
BRS1-FM4-PM11 — Excitotoxicity Modulationmodulates · Relationship Strength: Low · Evidence: Low
BRS2-FM2-PM5 — Transsulfuration Pathwayindirect · Relationship Strength: Low · Evidence: Low
BRS2-FM2-PM6 — Glutathione Synthesismodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS4-FM1-PM2 — NAD⁺ Metabolismindirect · Relationship Strength: Low · Evidence: Low
BRS4-FM1-PM3 — Creatine–Phosphocreatine Energy Bufferingindirect · Relationship Strength: Low · Evidence: Low
BRS4-FM2-PM4 — ROS Production and Controlmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS4-FM2-PM5 — Mitochondrial Protection (Redox Integrity)modulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS4-FM4-PM9 — Mitochondrial Biogenesismodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
PH006Stress ResilienceCapacity to buffer, adapt to, and recover from stress exposure.TA001 ★TA002TA003TA006Low–Medium
9 mechanisms
BRS-X(ECS-PM1) — NAPE → NAE Biosynthesis Capacitymodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS-X(ECS-PM2) — Omega-3-Derived Endocannabinoidome Signallingmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS-X(ECS-PM3) — FAAH-Mediated Endocannabinoid Preservationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS-X(ECS-PM5) — Endocannabinoid Stress-Buffering Capacitysupports · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS1-FM1-PM5 — Serotonergic Signalling Regulationsupports · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS2-FM2-PM6 — Glutathione Synthesismodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM2-PM3 — Nrf2-Mediated Cellular Defence Regulationmodulates · Relationship Strength: Low · Evidence: Low
BRS3-FM2-PM6 — Antioxidant Network Recyclingmodulates · Relationship Strength: Low–Medium · Evidence: Medium
BRS4-FM2-PM5 — Mitochondrial Protection (Redox Integrity)modulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
PH008Sleep / Calming ToneCapacity to downshift arousal and support sleep-compatible physiological regulation.TA001 ★TA002TA004TA006Low–Medium
3 mechanisms
BRS-X(Hormones-PM3) — Progesterone-Supportive Microbial Metabolismindirect · Relationship Strength: Low · Evidence: Low
BRS1-FM1-PM5 — Serotonergic Signalling Regulationsupports · Relationship Strength: Medium · Evidence: Low
BRS1-FM4-PM9 — GABA Synthesis Capacitymodulates · Relationship Strength: High · Evidence: Low
PH009Reward RegulationCapacity to regulate reward sensitivity, reinforcement learning, and reward-seeking behaviour.TA001 ★TA002TA003TA007Low
2 mechanisms
BRS-X(ECS-PM4) — Endocannabinoid–Dopamine Neuromodulationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS1-FM1-PM5 — Serotonergic Signalling Regulationmodulates · Relationship Strength: Low · Evidence: Low
PH010Behavioural ActivationCapacity to translate motivation into action, task initiation, and sustained behavioural engagement.TA001 ★TA003TA007Low
1 mechanism
BRS-X(ECS-PM4) — Endocannabinoid–Dopamine Neuromodulationmodulates · Relationship Strength: Low · Evidence: Low
PH011Cognitive ClarityCapacity to maintain clear, organised mental processing without excessive fog or confusion.TA001 ★TA002TA003TA004TA005TA006TA007Low–Medium
19 mechanisms
BRS-X(ECS-PM2) — Omega-3-Derived Endocannabinoidome Signallingmodulates · Relationship Strength: Low · Evidence: Low
BRS-X(Hormones-PM1) — Oestrogen Signalling Stabilitymodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS-X(Hormones-PM2) — Estrobolome Regulationindirect · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS1-FM2-PM6 — Acetylcholine Synthesis Supportmodulates · Relationship Strength: Medium · Evidence: Low
BRS1-FM3-PM7 — Neuronal Membrane DHA Incorporationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS1-FM4-PM10 — Glutamate Clearance & Recyclingmodulates · Relationship Strength: Low · Evidence: Low
BRS2-FM1-PM1 — Folate/B12-Dependent Homocysteine Remethylationmodulates · Relationship Strength: Low–Medium · Evidence: Low
BRS2-FM1-PM2 — Betaine/BHMT Remethylationindirect · Relationship Strength: Low · Evidence: Low
BRS2-FM1-PM3 — SAMe Synthesismodulates · Relationship Strength: Medium · Evidence: Low–Medium
BRS2-FM1-PM4 — Methionine Cycle Fluxmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS2-FM3-PM7 — Phosphatidylcholine Formationmodulates · Relationship Strength: Medium · Evidence: Low–Medium
BRS3-FM1-PM1 — NF-kB Signalling Regulationmodulates · Relationship Strength: Low–Medium · Evidence: Medium
BRS3-FM1-PM2 — Gut-Derived Inflammatory Signallingmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM2-PM3 — Nrf2-Mediated Cellular Defence Regulationmodulates · Relationship Strength: Low–Medium · Evidence: Medium
BRS3-FM2-PM4 — ROS Generation vs Clearance Balancemodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM2-PM5 — Lipid Peroxidation Controlmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM2-PM6 — Antioxidant Network Recyclingmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM3-PM7 — Cytokine Network Modulationmodulates · Relationship Strength: Low · Evidence: Low–Medium
BRS3-FM3-PM8 — Eicosanoid / SPM Balancemodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
PH014Hormonal VolatilityStability of hormone-linked signalling patterns that influence mood, cognition, and physiological regulation.TA001 ★TA002TA003TA004Low–Medium
2 mechanisms
BRS-X(Hormones-PM2) — Estrobolome Regulationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS-X(Hormones-PM4) — Metabolic-Reproductive Hormone Integrationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
PH015Stress ReactivityIntensity and pattern of physiological and affective responses to stressors.TA001 ★TA002TA004TA006Low–Medium
4 mechanisms
BRS-X(Hormones-PM3) — Progesterone-Supportive Microbial Metabolismindirect · Relationship Strength: Low · Evidence: Low
BRS1-FM4-PM11 — Excitotoxicity Modulationmodulates · Relationship Strength: Low · Evidence: Low
BRS2-FM2-PM5 — Transsulfuration Pathwaymodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS4-FM2-PM4 — ROS Production and Controlmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
PH016Apprehensive Worry / Perseverative ThoughtCapacity to limit sustained apprehensive worry, rumination, and difficulty disengaging from threat-anticipatory or negative perseverative thought.TA001 ★TA002TA003TA006Medium
6 mechanisms
BRS1-FM1-PM5 — Serotonergic Signalling Regulationsupports · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS1-FM4-PM9 — GABA Synthesis Capacitymodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM1-PM1 — NF-kB Signalling Regulationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM1-PM2 — Gut-Derived Inflammatory Signallingmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM3-PM7 — Cytokine Network Modulationmodulates · Relationship Strength: Medium · Evidence: Medium
BRS3-FM3-PM8 — Eicosanoid / SPM Balancemodulates · Relationship Strength: Medium · Evidence: Medium
PH017Pleasure & Interest CapacityCapacity to experience interest, anticipatory pleasure, and consummatory engagement with rewarding or meaningful activities — the functional domain overlapping anhedonia in depressive and related conditions.TA001 ★TA002TA003TA007Low–Medium
5 mechanisms
BRS1-FM1-PM4 — Noradrenergic Signallingmodulates · Relationship Strength: Low–Medium · Evidence: Low
BRS1-FM1-PM5 — Serotonergic Signalling Regulationmodulates · Relationship Strength: Low–Medium · Evidence: Low–Medium
BRS3-FM1-PM1 — NF-kB Signalling Regulationmodulates · Relationship Strength: Low · Evidence: Low–Medium
BRS3-FM3-PM7 — Cytokine Network Modulationmodulates · Relationship Strength: Low · Evidence: Low–Medium
BRS3-FM3-PM8 — Eicosanoid / SPM Balancemodulates · Relationship Strength: Low · Evidence: Low–Medium
PH018Social Engagement CapacityCapacity for affiliative approach, social participation, and maintained engagement in interpersonal contexts without excessive withdrawal or avoidance.TA002TA003TA004TA007Low–Medium
3 mechanisms
BRS1-FM1-PM5 — Serotonergic Signalling Regulationmodulates · Relationship Strength: Low · Evidence: Low
BRS1-FM4-PM9 — GABA Synthesis Capacityindirect · Relationship Strength: Low · Evidence: Low
BRS3-FM1-PM2 — Gut-Derived Inflammatory Signallingindirect · Relationship Strength: Low · Evidence: Low–Medium

Phenome details

Each registered phenome has a dedicated detail page with provenance, cross-references, foundational evidence, and connected mechanisms. Browse from the Phenome details section in the sidebar, or open a phenome from the table above.

Registry review flags

The following phenome pairs are flagged for manual review (not merged automatically).

  • RF002 (related_distinct): Stress Resilience (adaptive capacity) vs Stress Reactivity (response intensity) — related but not identical; do not merge automatically. — Stress Resilience / Stress Reactivity
  • RF003 (related_distinct): Motivation/Drive vs Behavioural Activation — related; remain separate unless manually merged. — Motivation / Drive / Behavioural Activation
  • RF004 (related_distinct): Emotional Regulation (affective modulation) vs Apprehensive Worry (sustained apprehensive/ruminative cognition) — RDoC Negative Valence / cognitive control overlap; remain separate. — Emotional Regulation / Apprehensive Worry / Perseverative Thought
  • RF005 (related_distinct): Reward Regulation (sensitivity, learning, seeking) vs Pleasure & Interest Capacity (experienced interest/pleasure and consummatory engagement) — RDoC Positive Valence / anhedonia domain; remain separate. — Reward Regulation / Pleasure & Interest Capacity
  • RF006 (related_distinct): Emotional Regulation vs Social Engagement Capacity (affiliation, approach, participation) — RDoC Social Processes; remain separate. — Emotional Regulation / Social Engagement Capacity