Genetic Architecture of AuDHD

Overview

Anthony's conditions (AuDHD, trichotillomania, HFE compound heterozygosity) intersect at multiple genetic levels. This note maps the key genetic pathways and their interactions.

flowchart TD
    subgraph Loci["Genetic Loci"]
        COMT["COMT Val158Met"]
        MTHFR["MTHFR C677T/A1298C"]
        SLC6A3["SLC6A3 / DAT1"]
        HFE["HFE C282Y/H63D"]
        SLC6A4["SLC6A4 / 5-HTTLPR"]
        SAPAP3["SAPAP3 / SLITRK1"]
    end

    subgraph Pathways["Molecular Pathways"]
        DA["Dopamine"]
        SE["Serotonin"]
        GL["Glutamate"]
        FE["Iron homeostasis"]
        ME["Methylation / SAMe"]
    end

    subgraph Phenotypes["Clinical Phenotypes"]
        ADHD["ADHD-PI"]
        ASD["Autism"]
        TTM["Trichotillomania"]
    end

    COMT --> DA
    SLC6A3 --> DA
    MTHFR --> ME
    HFE --> FE
    SLC6A4 --> SE
    SAPAP3 --> GL

    ME --> DA
    ME --> SE
    FE --> DA
    FE --> GL
    HFE --> GL

    DA --> ADHD
    DA --> ASD
    SE --> ASD
    SE --> TTM
    GL --> TTM
    GL --> ASD
    FE --> ADHD

    classDef locus fill:#85c1e9,stroke:#2471a3,color:#0a1929
    classDef pathway fill:#85c1e9,stroke:#2471a3,color:#0a1929
    classDef pheno fill:#f7dc6f,stroke:#b7950b,color:#1a1400

    class COMT,MTHFR,SLC6A3,HFE,SLC6A4,SAPAP3 locus
    class DA,SE,GL,FE,ME pathway
    class ADHD,ASD,TTM pheno

HFE Variants and Neurodevelopment

Beyond Iron Loading

The HFE gene (chromosome 6p21.3) is best known for haemochromatosis, but its effects extend to brain function:

• HFE polymorphisms and brain iron: C282Y and/or H63D carriers display higher iron load in putamen and higher transferrin saturation (Kalpouzos G et al. Neuropsychopharmacol Rep 2021;41(3):393-404, PMC8411306)
• Paradox: in carriers, higher putamen iron may be beneficial for cognitive performance at younger ages but detrimental with accumulation
• HFE and autism: Gebril OH et al. Disease Markers 2011 — studied HFE gene polymorphisms and autism risk in Egyptian children; found no significant direct association but noted elevated oxidative stress markers in autistic children with HFE variants
• HFE and lead/ADHD interaction: Nigg JT et al. Biol Psychiatry 2016 — HFE mutations modulate the effects of environmental lead on ADHD symptoms, suggesting gene-environment interaction (PMC4919074)
• Indian autism cohort: C282Y and H63D not found to be direct risk factors for autism in a targeted study (ScienceDirect 2022)

Clinical Relevance for Anthony

HFE C282Y/H63D likely doesn't cause his AuDHD, but may modify it through:

• Altered brain iron distribution affecting dopaminergic circuits
• Increased oxidative stress vulnerability
• Modified response to environmental factors
• Potential interaction with other neurodevelopmental risk genes on chromosome 6 (HLA region — immune/inflammatory genes)

MTHFR and Folate Metabolism

The Methylation Connection

MTHFR (methylenetetrahydrofolate reductase) converts folate to its bioavailable form, methylfolate. Methylfolate is essential for:

• Neurotransmitter synthesis: dopamine, serotonin, norepinephrine all require methylation steps
• DNA methylation: epigenetic regulation of gene expression
• Homocysteine metabolism: elevated homocysteine is neurotoxic
• SAMe production: S-adenosylmethionine is the universal methyl donor

MTHFR and Neurodevelopment

• MTHFR C677T and A1298C polymorphisms reduce enzyme activity by 30-70%
• Decreased MTHFR activity seen in: schizophrenia, bipolar disorder, depression, ASD, and ADHD
• MTHFR deficiency in siblings with autism AND ADHD documented (PMC10106103)
• Folate is a building block for serotonin, dopamine, and norepinephrine synthesis
• MTHFR A1298C is particularly linked to ADHD-PI — 7.4-fold increase in ADHD risk vs 1.3-fold for C677T (Gokcen C et al. Int J Med Sci 2011;8(7):523-528. PMC3167178)
• Meta-analysis of 25 studies confirmed MTHFR C677T significantly associated with ASD in five genetic models (Pu D et al. BMC Pediatr 2020;20(1):449. PMID: 32972375)

Anthony's Folate Supplementation

• He takes Holland & Barrett folate — this is significant
• Key question: Is he taking folic acid or methylfolate (5-MTHF)?
  • Folic acid requires MTHFR to convert → if MTHFR is impaired, folic acid may be less effective
  • Methylfolate (5-MTHF) bypasses MTHFR entirely
• Recommendation: Consider MTHFR genotyping to determine optimal folate form
• RCT evidence: L-methylfolate did not show clear benefit over placebo for ADHD (PMC6750952), but the theoretical pathway remains plausible for individuals with confirmed MTHFR variants

Dopamine Pathway Genes

COMT Val158Met

• COMT is the primary dopamine clearance mechanism in prefrontal cortex (DAT is sparse there)
• Val allele → higher enzyme activity → faster dopamine degradation → lower prefrontal dopamine
• Met allele → lower activity → slower degradation → higher prefrontal dopamine
• ADHD association: Meta-analysis shows mixed results; Val158Met may not directly confer ADHD risk but modulates the phenotype (PMC7710242)
• Working memory: COMT genotype × ADHD interaction on working memory performance (Mish JG et al. 2014, PMID: 25007787)
• Iron-COMT interaction: COMT uses magnesium as primary divalent cation cofactor, but Fe(II) can serve as an alternative with reduced efficiency. Fe(III) inhibits COMT — in Anthony's iron-overloaded state, excess Fe(III) could paradoxically increase prefrontal dopamine (Rutherford K et al. PLOS ONE 2013;8(6):e67325. PMC3466255)

DAT1/SLC6A3 (Dopamine Transporter)

• 10-repeat allele of the 3'UTR VNTR associated with ADHD
• DAT density determines stimulant response (Elvanse works partly by blocking DAT)
• DAT is sparse in prefrontal cortex but dense in striatum — relevant for ADHD subtype differences

DRD4 (Dopamine Receptor D4)

• 7-repeat allele associated with ADHD, novelty-seeking
• More relevant to ADHD-Combined than ADHD-PI
• May be less relevant for Anthony's inattentive presentation

Serotonin Pathway Genes

SLC6A4 (Serotonin Transporter, 5-HTTLPR)

• Short allele → reduced serotonin reuptake → altered serotonergic tone
• Associated with anxiety, depression, OCD-spectrum features
• Relevant to TTM via serotonergic modulation of repetitive behaviours
• May explain why SSRIs have variable efficacy in TTM
• Allelic heterogeneity in SLC6A4 confers susceptibility to autism and rigid-compulsive behaviours — four coding substitutions and 15 noncoding variants were preferentially transmitted in families with increased rigid-compulsive behaviours with autism (Sutcliffe JS et al. Am J Hum Genet 2005;77(2):265-279. PMID: 15995945)

HTR2A (Serotonin 2A Receptor)

• Polymorphisms associated with OCD-spectrum conditions
• Modulates the phosphoinositide signalling pathway (targeted by inositol)

Trichotillomania-Specific Genes

SAPAP3/DLGAP3

• Post-synaptic scaffold protein at glutamatergic synapses in cortico-striatal circuits
• Animal knockouts → compulsive self-grooming
• Human variants associated with OCD-spectrum conditions including TTM
• Link to iron: glutamate synapse function is influenced by iron status

SLITRK1

• Controls neurite outgrowth in cortico-striatal circuits
• Variants associated with TTM and Tourette syndrome
• Involved in synapse formation during neurodevelopment

HoxB8

• Expressed in microglia and cortico-striatal circuits
• HoxB8 knockout mice show pathological grooming
• Microglial connection: microglia are the brain's immune cells and are iron-responsive
• Iron overload activates microglia → neuroinflammation → potential BFRB exacerbation

Shared Genetic Architecture: Autism × ADHD

GWAS Findings

• Significant genetic correlation between autism and ADHD at the genome-wide level (genetic correlation of 0.365 from common variation)
• Shared loci include genes involved in:
  • Synaptic function
  • Neurodevelopmental timing
  • Immune regulation
  • Chromatin remodeling
• The late-diagnosis autism genetic profile shows stronger correlation with ADHD genetics than the early-diagnosis profile (Warrier et al. Nature 2025)
• Shared risk genes identified: SORCS3, PTBP2 (neural RNA-binding protein critical for alternative splicing), MANBA, DPYD, INSM1, PAX1 — all showing prominent brain expression (Olieman ES et al. Nat Genet 2024;56(2):326-337. PMC10848300)
• CDH2 (N-cadherin) mutations cause ADHD in humans and mice; the broader cadherin family (CDH13) is implicated in both autism and ADHD (Halperin D et al. Nat Commun 2021;12(1):6187)

Implications

• Anthony's AuDHD likely involves shared genetic variants rather than two independent conditions
• This has treatment implications: interventions targeting shared pathways may address both conditions

Pharmacogenomics — Elvanse Response

Lisdexamfetamine Metabolism

• Lisdexamfetamine is a prodrug → converted to d-amphetamine by red blood cell enzymes
• This conversion is not CYP-dependent — unusual and means fewer drug interactions
• However, CYP2D6 is involved in downstream d-amphetamine metabolism (4-hydroxylation); poor metabolisers may have higher drug exposure and higher odds of symptom improvement (Carvalho M et al. J Am Acad Child Adolesc Psychiatry 2024;63(8):S277. PMID: 38517706)
• Downstream effects are also modulated by:
  • COMT — determines prefrontal dopamine clearance rate
  • DAT1 — determines striatal dopamine reuptake efficiency
  • ADRA2A — alpha-2 adrenergic receptor; affects norepinephrine response; ADRA2A -1291C>G specifically associated with treatment response in ADHD-PI (Cheon K-A et al. J Neural Transm 2009;116(2):205-212)

Iron and Stimulant Response

• Putamen iron correlates with methylphenidate responsiveness (Cascone AD et al. Dev Cogn Neurosci 2023;63:101274)
• Brain iron status may predict which patients respond best to stimulants
• Anthony's systemic iron overload + potentially altered brain iron distribution may affect his Elvanse response

Epigenetic Considerations

Iron and Epigenetics

• Iron overload affects epigenetic machinery:
  • TET enzymes (DNA demethylation) are iron-dependent
  • Jumonji domain histone demethylases require iron as cofactor
  • Excess iron may dysregulate gene expression through altered methylation patterns
• This provides a mechanism for iron overload to influence neurodevelopmental gene expression beyond direct neurotoxicity
• Brain iron overload specifically reduces global DNA methylation and attenuates DNA methyltransferase activity, with downstream effects on GABAergic neurotransmission (Ye Q et al. FASEB J 2019;33(3):3815-3826)
• Multigenerational effects: Iron deficiency in one generation alters epigenetic programming of BDNF in subsequent generations — Anthony's paternal HFE inheritance means his father's iron metabolism may have influenced epigenetic programming during development (Tran PV et al. Physiol Genomics 2013;45(11):478-487)

Methylation and Neurodevelopment

• SAMe (from folate/MTHFR pathway) is the universal methyl donor
• Disrupted methylation → altered expression of dopamine, serotonin, and glutamate pathway genes
• Anthony's folate supplementation may be partially compensating for methylation deficits

Testing Recommendations

Verified Academic Citations

HFE Variants and Brain Function

1. Mitchell RM, Lee SY, Simmons Z, Connor JR. "HFE polymorphisms affect cellular glutamate regulation." Neurobiol Aging 2011;32(6):1114-23. DOI: 10.1016/j.neurobiolaging.2009.05.016 | PMID: 19560233

   • H63D HFE cells show increased glutamate release and reduced glutamate uptake capacity, demonstrating effects of HFE beyond iron regulation. Suggests H63D may promote glutamate toxicity.

2. Nandar W, Connor JR. "HFE gene variants affect iron in the brain." J Nutr 2011;141(4):729S-739S. DOI: 10.3945/jn.110.130351 | PMID: 21346098

   • Reviews how HFE gene mutations (C282Y, H63D) lead to loss of iron homeostasis in the brain and increased oxidative stress, relevant to neurodegenerative disease.

3. Nandar W, Neely EB, Unger E, Connor JR. "A mutation in the HFE gene is associated with altered brain iron profiles and increased oxidative stress in mice." Biochim Biophys Acta 2013;1832(6):729-41. DOI: 10.1016/j.bbadis.2013.02.009 | PMID: 23429074

   • H67D mice (homologous to human H63D) show significantly altered brain iron management protein expression and increased oxidative stress, even without total brain iron increase.

4. Jahanshad N, Kohannim O, Hibar DP et al. "Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene." Proc Natl Acad Sci USA 2012;109(14):E851-9. DOI: 10.1073/pnas.1105543109 | PMID: 22232660

   • In 615 healthy adults, H63D carriers showed brain structural differences linked to transferrin-mediated iron transport. Demonstrates that HFE variants influence brain structure in healthy people.

5. Marshall Moscon SL, Connor JR. "HFE Mutations in Neurodegenerative Disease as a Model of Hormesis." Int J Mol Sci 2024;25(6):3334. DOI: 10.3390/ijms25063334 | PMID: 38542306 | PMC: PMC10970347

   • H63D HFE may confer hormetic neuroprotection: chronic low-level iron-induced stress triggers adaptive responses that protect against future insults. Proteins that regulate glutamate signalling are increased in H63D HFE cells. First hormetic model for HFE in neurodegeneration.

6. Wang C, Martins-Bach AB, Alfaro-Almagro F et al. "Phenotypic and genetic associations of quantitative magnetic susceptibility in UK Biobank brain imaging." Nat Neurosci 2022;25(6):818-31. DOI: 10.1038/s41593-022-01074-w | OpenAlex: W4281288363

   • QSM-based brain iron quantification in 35,273 UK Biobank participants. Identified associations of brain iron with 251 phenotypes including neuropsychiatric traits, and genetic associations with iron-related loci.

MTHFR, Folate and Neurodevelopment

7. Meng X, Zheng JL, Sun ML et al. "Association between MTHFR (677C>T and 1298A>C) polymorphisms and psychiatric disorder: A meta-analysis." PLoS One 2022;17(7):e0271170. DOI: 10.1371/journal.pone.0271170 | PMID: 35834596 | PMC: PMC9282595

   • Meta-analysis of MTHFR polymorphisms across ADHD, bipolar disorder, and schizophrenia. Found MTHFR 1298A>C associated with ADHD and bipolar disorder; 677C>T associated with bipolar and schizophrenia. 5 ADHD studies (434 cases/670 controls).

8. Khan S, Naeem A. "MTHFR Deficiency in Biological Siblings Diagnosed With Autism and Attention-Deficit Hyperactivity Disorder (ADHD): A Report of Two Cases." Cureus 2023;15(3):e36294. DOI: 10.7759/cureus.36294 | PMID: 37073207

   • Two siblings with both autism and ADHD found to have MTHFR deficiency. Highlights under-testing of MTHFR in neurodevelopmental presentations and benefit of folate supplementation.

9. Lintas C, Cassano I, Azzara A et al. "Maternal Epigenetic Dysregulation as a Possible Risk Factor for Neurodevelopmental Disorders." Genes (Basel) 2023;14(3):585. DOI: 10.3390/genes14030585 | PMID: 36980856

   • Reviews how maternal epigenetic dysregulation, including folate/methylation pathway disruption, may contribute to neurodevelopmental disorder risk in offspring.

COMT and Dopamine Metabolism

10. Qian QJ, Liu J, Wang YF et al. "ADHD comorbid ODD and its predominantly inattentive type: evidence for an association with COMT but not MAOA in a Chinese sample." Behav Brain Funct 2009;5:8. DOI: 10.1186/1744-9081-5-8 | PMID: 19228412

    • COMT Val158Met associated with ADHD-inattentive type comorbid with ODD. Supports COMT involvement specifically in inattentive presentations.

11. Abraham E, Scott MA, Blair C. "COMT Val158Met Genotype and Early-Life Family Adversity Interactively Affect ADHD Symptoms Across Childhood." Front Genet 2020;11:724. DOI: 10.3389/fgene.2020.00724 | PMID: 32765586

    • Prospective study showing gene-environment interaction: COMT Val158Met genotype interacts with early adversity to modulate ADHD symptom trajectories across childhood.

12. Spoto G, Di Rosa G, Nicotera AG. "The Impact of Genetics on Cognition: Insights into Cognitive Disorders and Single Nucleotide Polymorphisms." J Pers Med 2024;14(2):156. DOI: 10.3390/jpm14020156 | PMID: 38392589

    • Reviews SNPs including COMT, MTHFR, and dopamine pathway genes in relation to cognitive function and neuropsychiatric disorders. Emphasises prefrontal dopaminergic circuit regulation.

Shared Genetic Architecture: Autism x ADHD x Psychiatric Disorders

13. Demontis D, Walters GB, Athanasiadis G et al. "Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains." Nat Genet 2023;55(2):198-208. DOI: 10.1038/s41588-022-01285-8 | PMID: 36702997 | PMC: PMC10914347

    • Landmark ADHD GWAS meta-analysis (38,691 cases/186,843 controls). Identified 27 risk loci and 76 potential risk genes enriched in early brain development. 84-98% of ADHD-influencing variants shared with other psychiatric disorders. Risk enriched in midbrain dopaminergic neurons.

14. Grotzinger AD, Werme J, Peyrot WJ et al. "Mapping the genetic landscape across 14 psychiatric disorders." Nature 2025;649(8096):406-415. DOI: 10.1038/s41586-025-09820-3 | PMID: 41372416 | PMC: PMC12779569

    • Cross-disorder GWAS of 1,056,201 cases across 14 psychiatric disorders. Identified five genomic factors explaining ~66% of genetic variance and 238 pleiotropic loci. ADHD and autism load onto shared factors. Shared signal enriched in excitatory neurons.

15. Hegemann L, Corfield EC, Askelund AD et al. "Genetic and phenotypic heterogeneity in early neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study." Mol Autism 2024;15(1):24. DOI: 10.1186/s13229-024-00599-0 | PMID: 38849897

    • Population-based study exploring shared genetic liability between autism and ADHD traits, confirming overlapping genetic architecture at the sub-diagnostic level.

Trichotillomania Genetics

16. Reid M, Lin A, Farhat LC et al. "The genetics of trichotillomania and excoriation disorder: A systematic review." Compr Psychiatry 2024;133:152506. DOI: 10.1016/j.comppsych.2024.152506 | PMID: 38833896

    • Systematic review of TTM genetics. Evaluates candidate genes (SAPAP3, SLITRK1, SLC6A4, HoxB8) and serotonergic/glutamatergic pathway involvement. Highlights need for larger GWAS.

17. Halvorsen MW, Garrett ME, Cuccaro ML et al. "Genomic Analysis of Trichotillomania." medRxiv 2025. DOI: 10.1101/2025.01.23.25321045 | PMID: 39974061 | PMC: PMC11839004

    • First formal GWAS of TTM (101 cases/488 controls). TTM cases carry higher polygenic risk for psychiatric disorders. Found neuropsychiatric-associated CNVs (NRXN1 deletions, 15q11.2 deletions) in TTM cases. Preprint.

18. Zuchner S, Cuccaro ML, Tran-Viet KN et al. "SLITRK1 mutations in trichotillomania." Mol Psychiatry 2006;11(10):887-9. DOI: 10.1038/sj.mp.4001898 | PMID: 17003809

    • Identified SLITRK1 mutations in TTM patients, linking TTM to Tourette syndrome genetics via shared cortico-striatal circuit genes.

19. Zuchner S, Wendland JR, Ashley-Koch AE et al. "Multiple rare SAPAP3 missense variants in trichotillomania and OCD." Mol Psychiatry 2009;14(1):6-9. DOI: 10.1038/mp.2008.83 | PMID: 19096451

    • Identified multiple rare SAPAP3 missense variants in TTM and OCD patients. SAPAP3 is a post-synaptic scaffold protein at glutamatergic synapses in cortico-striatal circuits.

20. Hatayama M, Aruga J. "Developmental control of noradrenergic system by SLITRK1 and its implications in the pathophysiology of neuropsychiatric disorders." Front Mol Neurosci 2023;15:1080739. DOI: 10.3389/fnmol.2022.1080739 | PMID: 36683853

    • SLITRK1 controls noradrenergic neuron development and synapse formation. Links TTM/Tourette syndrome to noradrenergic developmental abnormalities.

21. Lamothe H, Schreiweis C, Mondragon-Gonzalez LS et al. "The Sapap3-/- mouse reconsidered as a comorbid model expressing a spectrum of pathological repetitive behaviours." Transl Psychiatry 2023;13(1):35. DOI: 10.1038/s41398-023-02323-7 | PMID: 36717540

    • Sapap3 knockout mice display a spectrum of repetitive behaviours spanning OCD and Tourette-like phenotypes, supporting shared cortico-striatal pathology across OCD-spectrum disorders including TTM.

22. Wang Y, Yu J, Ma R et al. "Exploring the nucleus accumbens circuit and oxytocin therapy in a Sapap3 knockout mouse model of trichotillomania." Sci Rep 2025;15(1):28492. DOI: 10.1038/s41598-025-14076-y | PMID: 40764792 | PMC: PMC12325644

    • Sapap3 KO mice show TTM-like behaviour, NAc neuronal hypoactivity, increased dopamine, and D1/D2 receptor alterations. SHANK3 compensatory upregulation observed. Female KO mice showed greater grooming severity.

Pharmacogenomics — Stimulant Response

23. Bishop JR, Zhou C, Gaedigk A et al. "Dopamine Transporter and CYP2D6 Gene Relationships with ADHD Treatment Response in the Methylphenidate and Atomoxetine Crossover Study." J Child Adolesc Psychopharmacol 2024;34(10):458-469. DOI: 10.1089/cap.2024.0069 | PMID: 39387268 | PMC: PMC11807865

    • CYP2D6 phenotype and DAT1 3'UTR VNTR genotype modify ADHD treatment dose-response. DAT1 9/10 genotype showed more rapid atomoxetine response. Genotyping may have limited clinical utility for methylphenidate/atomoxetine as both were effective at higher doses.

24. Thirstrup JP, Duan J, Ribases Haro M et al. "Common and rare variant contributions to discontinuation of stimulant treatment in ADHD." Transl Psychiatry 2026;16(1). DOI: 10.1038/s41398-026-03925-7 | PMID: 41764167 | PMC: PMC12987951

    • GWAS of stimulant discontinuation in 18,362 ADHD patients. 39% discontinued within one year. Higher psychiatric PGS predicted discontinuation. Reduced burden of dopamine-related protein-truncating variants associated with discontinuation.

25. Ward K, Citrome L. "Lisdexamfetamine: chemistry, pharmacodynamics, pharmacokinetics, and clinical efficacy, safety, and tolerability." Expert Opin Drug Metab Toxicol 2018;14(2):229-247. DOI: 10.1080/17425255.2018.1420163 | PMID: 29258368

    • Comprehensive pharmacology review of lisdexamfetamine. Confirms prodrug conversion to d-amphetamine is enzyme-mediated in red blood cells and not CYP-dependent.

Iron and Epigenetics

26. Gao X, Song Y, Wu J et al. "Iron-dependent epigenetic modulation promotes pathogenic T cell differentiation in lupus." J Clin Invest 2022;132(9):e152345. DOI: 10.1172/JCI152345 | PMID: 35499082

    • Demonstrated that iron overload drives epigenetic reprogramming via TET enzymes and Jumonji histone demethylases, altering DNA methylation patterns and T cell differentiation. Provides mechanistic evidence for iron-dependent epigenetic modulation.

27. Blanquart C, Linot C, Cartron PF et al. "Epigenetic Metalloenzymes." Curr Med Chem 2019;26(15):2748-85. DOI: 10.2174/0929867325666180706105903 | PMID: 29984644

    • Reviews iron- and zinc-dependent epigenetic metalloenzymes including TET dioxygenases (DNA demethylation) and Jumonji-domain histone demethylases. Both families require iron(II) as cofactor — iron overload or deficiency can dysregulate epigenetic gene expression.

28. Bach MV, Coutts RT, Baker GB. "Involvement of CYP2D6 in the in vitro metabolism of amphetamine, two N-alkylamphetamines and their 4-methoxylated derivatives." Xenobiotica 1999;29(7):719-32. DOI: 10.1080/004982599238344 | PMID: 10456690

    • Demonstrated CYP2D6 catalyses ring hydroxylation of amphetamine and derivatives. Relevant to downstream metabolism of d-amphetamine (active metabolite of lisdexamfetamine).

Cross-References

• HFE Compound Heterozygosity
• Iron-Dopamine-ADHD Axis
• HFE Variants and Brain Iron
• Trichotillomania and Neurodevelopmental Links
• Late-Diagnosed Autism - Distinct Profile
• ADHD-PI and Internal Hyperactivity
• Copper-Zinc-Iron Interactions
• Elvanse and Mineral Metabolism
• Tryptophan-Kynurenine Pathway