MTHFR, Spina Bifida , ADHD and Autism.

Folate Metabolism Gene 5,10-Methylenetetrahydrofolate Reductase (MTHFR) Is Associated with ADHD in Myelomeningocele Patients

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0051330

The objective of this study was to examine the relation between the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene and behaviors related to attention- deficit/hyperactivity disorder (ADHD) in individuals with myelomeningocele.

* myelomeningocele – http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002525/

The rationale for the study was twofold: folate metabolizing genes, (e.g. MTHFR), are important not only in the etiology of neural tube defects but are also critical to cognitive function; and individuals with myelomeningocele have an elevated incidence of ADHD.

Here, we tested 478 individuals with myelomeningocele for attention-deficit hyperactivity disorder behavior using the Swanson Nolan Achenbach Pelham-IV ADHD rating scale.

Myelomeningocele participants in this group for whom DNAs were available were genotyped for seven single nucleotide polymorphisms (SNPs) in the MTHFR gene. The SNPs were evaluated for an association with manifestation of the ADHD phenotype in children with myelomeningocele. The data show that 28.7% of myelomeningocele participants exhibit rating scale elevations consistent with ADHD; of these 70.1% had scores consistent with the predominantly inattentive subtype.

In addition, we also show a positive association between the SNP rs4846049 in the 3′-untranslated region of the MTHFR gene and the attention-deficit hyperactivity disorder phenotype in myelomeningocele participants.

These results lend further support to the finding that behavior related to ADHD is more prevalent in patients with myelomeningocele than in the general population. These data also indicate the potential importance of the MTHFR gene in the etiology of the ADHD phenotype.

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Further Reading

Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study.

Abstract

BACKGROUND:

Periconceptional folate is essential for proper neurodevelopment.

OBJECTIVE:

Maternal folic acid intake was examined in relation to the risk of autism spectrum disorder (ASD) and developmental delay (DD).

DESIGN:

Families enrolled in the CHARGE (CHildhood Autism Risks from Genetics and Environment) Study from 2003 to 2009 were included if their child had a diagnosis of ASD (n = 429), DD (n = 130), or typical development (TD; n = 278) confirmed at the University of California Davis Medical Investigation of Neurodevelopmental Disorders Institute by using standardized clinical assessments. Average daily folic acid was quantified for each mother on the basis of dose, brands, and intake frequency of vitamins, supplements, and breakfast cereals reported through structured telephone interviews.

RESULTS:

Mean (±SEM) folic acid intake was significantly greater for mothers of TD children than for mothers of children with ASD in the first month of pregnancy (P1; 779.0 ± 36.1 and 655.0 ± 28.7 μg, respectively; P < 0.01).

A mean daily folic acid intake of ≥600 μg (compared with <600 μg) during P1 was associated with reduced ASD risk (adjusted OR: 0.62; 95% CI: 0.42, 0.92; P = 0.02), and risk estimates decreased with increased folic acid (P-trend = 0.001).

The association between folic acid and reduced ASD risk was strongest for mothers and children with MTHFR 677 C>T variant genotypes.

A trend toward an association between lower maternal folic acid intake during the 3 mo before pregnancy and DD was observed, but not after adjustment for confounders.

CONCLUSIONS:

Periconceptional folic acid may reduce ASD risk in those with inefficient folate metabolism. The replication of these findings and investigations of mechanisms involved are warranted.

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This entry was posted in Autism, co-morbid, Epigenetics, Genetics, Immune System, Inflammation, Neurology, Physiology and tagged , , , , , , , , . Bookmark the permalink.

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