Disclaimer:

This information is intended solely for facilitating discussions with physicians and researchers regarding a personal, lab-test-driven treatment approach for neurodivergence. It was developed as a collaborative tool to support conversations with my primary care physician. This is not a self-help guide and should not be interpreted as professional medical advice for diagnosis, treatment,t ect.

Please note that the information provided here is based on personal experience and research, and while every effort has been made to ensure its accuracy, errors or omissions may exist. This summary is meant for reference purposes only, and any health-related decisions should be made in consultation with a licensed medical professional. Readers are encouraged to review verified, peer-reviewed source materials when considering any treatment options.

Neurodivergence Test and Treat:

A data-driven protocol for diagnosis and treatment of neurodivergence and its comorbidities.

1. Metabolic Evaluation:

Plasma or Urine Tests: Conduct to assess metabolic function and identify disruptions in the one-carbon pathway.

1. Vitamin Deficiency Screening: Focus on methylation cofactors such as B vitamins (B12, B9, B6, B3, Iron [Anima panel]).
2. Methylation Disruption Screening: Evaluate the folate and methionine cycles for inefficiencies or blockages.
3. Neurotransmitter Dysregulation: Screen for abnormalities in synthesis and catabolism, which are critical for neurodivergent conditions.

2. Genetic Evaluation:

a) Genetic Sequencing and Analysis: Target key genes and mutations linked to neurodivergence, distinguishing between sequencing (identifying genetic material) and analysis (interpreting genetic data).

b) Identification of Genetic Markers: Analyze data to pinpoint neurodivergence genetic markers affecting metabolite processing and transport.

3. Identification of Anomalies:

Metabolite Level Comparison: Utilize normative ranges to identify aberrant metabolite levels, paving the way for targeted interventions.

4. Pathway Analysis:

Affected Pathways Identification: Determine which biochemical cascades are impacted by observed anomalies.

5. Genetic Marker Correlation:

Analysis of Genetic Data: Correlate genetic markers with metabolic disruptions to map out the underlying causes of neurodivergence.

6. Hypothesis Development:

Pathway Correlation: Combine metabolic and genetic findings with established pathway maps to hypothesize potential interventions.

Treatment Planning and Implementation

7. Tailored Treatment Plan:

Personalized Interventions: Develop intervention strategies that aim to normalize metabolite levels, incorporating supplements, medications, and lifestyle adjustments as necessary.

8. Phased Treatment Implementation:

Gradual Intervention Rollout: Introduce treatments progressively, prioritizing patient tolerance and response to minimize adverse effects and optimize outcomes.

Monitoring and Adjustments

9. Continuous Monitoring:

Follow-Up Testing: Regularly assess metabolite levels to monitor the impact of the treatment plan, ensuring adjustments are made as needed.

10. Treatment Optimization: Responsive Adjustments for Maximum Benefit

Adaptive Dosing and Intervention: Modify treatment strategies based on ongoing metabolite response, patient feedback, and symptom evaluation, ensuring a responsive and patient-centered approach

Methylation Dysregulation Screening And Diagnostics

Minimum Testing:

· Metabolites: Homocysteine, B12, B9, B6, B3, D

· Genetics: MTHFR Gene: C677T & A1298C

Recommended Testing:

· Micronutrients, B-Vitamin Panel [Quest #10195, # 17306] B1, B2, B3, B5, B6, B9, B12, D

[LabCorp # B1 [121186], B2 [123220], B3 [070115], B5 [070086], B6 [004655], B9& B12 [000810], D [081950]]

· Comprehensive Methylation Panel, [Genova Diagnostics #methylation-panel] [Doctor's Data: Methylation Profile Methylation Profile] Methionine, Homocysteine, Cystathionine, SAH, Cysteine, SAMe

· Genomics: [Genova Diagnostics # Methylation Add-On:] [GeneticGenie.org #Methylation Profile]

MTHFR: C677T,A1298C, COMT: V158M, MTRR: A66G, MAT1A: D18777A, SHMT1: D18777A, MTR: A2756G, CBS: C699T, BHMT: G742A, GNMT: C1289T

Disruptions in the folate and methionine cycles significantly impact health, notably through cardiovascular, neurological, and perinatal complications:

Nutritional Deficiencies:
- Folate (B9): Crucial for DNA/RNA synthesis; its deficiency leads to megaloblastic anemia and elevated homocysteine levels, increasing cardiovascular disease risk.
- Vitamin B12: Acts as a cofactor for methionine synthase; deficiency disrupts homocysteine metabolism and causes megaloblastic anemia.
- Vitamin B6 (Pyridoxine): Involved in converting homocysteine to cysteine in the transculturation pathway; deficiency elevates homocysteine.
- Riboflavin (B2): A cofactor for MTHFR, essential for converting 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, critical in the methionine cycle; deficiency impairs homocysteine remethylation.
Genetic Factors:
- MTHFR Mutation: The C677T and A1298C mutations in the MTHFR gene reduce enzyme efficiency, leading to high homocysteine levels and compromised folate metabolism.
- Enzymatic Genetic Variants: Variants in methionine synthase (MS), methionine synthase reductase (MTRR), and cystathionine β-synthase (CBS) genes can also disrupt these cycles, with direct implications on homocysteine metabolism.
Pharmacological Agents:
- Antifolate Drugs: Such as methotrexate, inhibit folate pathways, leading to deficiencies and cycle disruption.
- Nitrous Oxide: Oxidizes cobalamin (vitamin B12), inhibiting its function and affecting methionine and folate cycles.
Alcohol Consumption: Impairs the absorption and metabolism of folate and vitamin B12, contributing to nutrient deficiencies and cycle disruptions.
Health Conditions:
- Malabsorption Syndromes: Like celiac disease, Crohn's disease, and gastric bypass surgery, reduce nutrient absorption, thereby affecting these cycles.
- Liver Diseases: Affect homocysteine metabolism and nutrient storage, leading to disruptions in these cycles.

Elevated Homocysteine: High homocysteine levels, or hyperhomocysteinemia, are implicated in endothelial dysfunction, oxidative stress, and increased thrombosis risk, contributing to cardiovascular disease pathogenesis.

Conclusion: The integrity of the folate and methionine cycles is paramount, necessitating a multifaceted approach addressing dietary, genetic, and health-related factors. Tailoring interventions to include dietary supplementation (B12, 5-MTHF, B6, B3, D), genetic screening (particularly for MTHFR mutations), and lifestyle modifications can mitigate health risks associated with these cycle disruptions. This comprehensive strategy underscores the importance of a holistic approach in patient care.

References:

Neurodivergence & Comorbidities Along the BH4 Pathway

Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review https://doi.org/10.1007/s40120-022-00392-2

ADHD symptoms in neurometabolic diseases: Underlying mechanisms and clinical implications

https://doi.org/10.1016/j.neubiorev.2021.11.012

Methylenetetrahydrofolate reductase and psychiatric diseases

https://doi.org/10.1038/s41398-018-0276-6

Folate–Methionine Cycle Disruptions in ASD Patients and
Possible Interventions: A Systematic Review

https://doi.org/10.3390/genes14030709

Improving Outcome in Infantile Autism with Folate Receptor Autoimmunity and Nutritional Derangements: A Self-Controlled Trial

| https://doi.org/10.1155/2019/7486431

The Key Role of Purine Metabolism in the Folate-Dependent Phenotype of Autism Spectrum Disorders: An In Silico Analysis

https://doi.org/10.3390/metabo10050184

Inborn Errors of Metabolism Associated With Autism Spectrum Disorders: Approaches to Intervention

https://doi.org/10.3389/fnins.2021.673600

Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies

https://doi.org/10.1186/s13023-020-01379-8

Comparison of Treatment for Metabolic Disorders Associated with Autism:Reanalysis of Three Clinical Trials

10.3389/fnins.2018.00019

A Metabolomics Approach to Screening for Autism Risk in the Children's Autism Metabolome Project

10.1002/aur.233