What is the relationship between Methylenetetrahydrofolate Reductase (MTHFR) mutation and Attention Deficit Hyperactivity Disorder (ADHD)?

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Last updated: April 20, 2025View editorial policy

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From the Guidelines

The MTHFR gene mutation may have a relationship with ADHD, though the connection is not fully established, and current evidence does not support altering the standard treatment approach for ADHD based on MTHFR status. This mutation affects the body's ability to convert folate into its active form (methylfolate), which is needed for numerous biochemical processes including neurotransmitter production and DNA methylation. Some research suggests that individuals with MTHFR variants, particularly the C677T polymorphism, might have an increased risk of developing ADHD symptoms due to altered folate metabolism affecting neurodevelopment and neurotransmitter function 1. However, the provided evidence does not directly address the relationship between MTHFR and ADHD, and the most recent study 1 focuses on pharmacological treatment options for ADHD in children and adolescents, without mentioning MTHFR.

Key points to consider:

  • The diagnostic process for ADHD relies on a comprehensive clinical interview, behavioral observation, and assessment tools, with no direct reference to genetic testing for MTHFR 1.
  • Standard ADHD medications, such as stimulants, remain the first-line treatment, and their effects on ADHD symptoms are well-documented 1.
  • While some healthcare providers might recommend supplementation with methylfolate and B12 for individuals with MTHFR mutations, these supplements are not FDA-approved treatments for ADHD and should only be taken under medical supervision.
  • The relationship between MTHFR and ADHD represents an area where genetics may influence neurological function, but more research is needed before specific treatment protocols based on MTHFR status become standard practice.

From the Research

MTHFR Mutation and ADHD

  • The relationship between MTHFR mutation and ADHD is not directly addressed in most of the provided studies, except for one study that investigated the MTHFR gene variants in the mothers of ADHD-affected children 2.
  • This study found that MTHFR gene expression levels were significantly higher in the mothers of ADHD-affected children compared to healthy control mothers, which could potentially contribute to the ADHD condition in their children 2.
  • However, there is no direct evidence to suggest that MTHFR mutation is a risk factor for ADHD, and further investigation is needed to confirm this association.

Treatment of ADHD

  • Several studies investigated the efficacy of different treatments for ADHD, including methylphenidate and atomoxetine 3, 4, 5, 6.
  • These studies found that both methylphenidate and atomoxetine are effective in reducing ADHD symptoms and improving executive functions in adults with ADHD 5, 6.
  • However, one study found that L-methylfolate supplementation had no significant effect on ADHD symptoms in adults, except for a suggestion of reduced efficacy of methylphenidate 4.

Genetic and Epigenetic Factors

  • The study on MTHFR gene variants in the mothers of ADHD-affected children suggests that genetic and epigenetic factors may play a role in the development of ADHD 2.
  • Further research is needed to investigate the relationship between genetic and epigenetic factors, including MTHFR mutation, and the development of ADHD.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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