Folic acid may mitigate autism risk from pesticides

 "In the paper, which used data from the Childhood Autism Risks from Genetics and the Environment (CHARGE) study, researchers looked at 296 children between 2 and 5 who had been diagnosed with ASD and 220 who had developed typically. Mothers were interviewed about their household pesticide exposure during pregnancy, as well as their folic acid and B vitamin intake. The team also linked data from California Pesticide Use reports, which provide important details about agricultural spraying, with the mothers' addresses.
Mothers who took less than 800 micrograms and encountered household pesticides had a much higher estimated risk of having a child who developed an ASD than moms who took 800 micrograms of folic acid or more and were not exposed to pesticides. The associated risk increased for women exposed repeatedly. Women with low folic acid intake who were exposed to agricultural pesticides during a window from three months before conception to three months afterward also were at higher estimated risk."



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Too much folate in pregnant women increases risk for autism, study suggests

Women who plan on becoming pregnant are told they need enough of the nutrient folate to ensure proper neurodevelopment of their babies, but new research from the Johns Hopkins Bloomberg School of Public Health suggests there could be serious risks in having far too much of the same nutrient.

The researchers found that if a new mother has a very high level of folate right after giving birth - more than four times what is considered adequate - the risk that her child will develop an autism spectrum disorder doubles. Very high vitamin B12 levels in new moms are also potentially harmful, tripling the risk that her offspring will develop an autism spectrum disorder. If both levels are extremely high, the risk that a child develops the disorder increases 17.6 times. Folate, a B vitamin, is found naturally in fruits and vegetables, while the synthetic version, folic acid, is used to fortify cereals and breads in the United States and in vitamin supplements.



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Folate concentrations during pregnancy and autistic traits in the offspring. The Generation R Study

In a population-based study, we examined the associations of maternal plasma folate concentrations at 13 weeks of gestation and prenatal folic acid supplement use with autistic traits in the offspring at the age of six years. Parent-reported autistic traits were assessed using the Social Responsiveness Scale short form. Maternal folate was not associated with autistic traits in the offspring. In contrast, prenatal folic acid use was associated with less child autistic traits. Future research should focus on the timing of the potential effect of prenatal folate on the development of autistic traits in combination with clinical diagnosis of autism in the offspring.

Epigenetics & Chromatin | Full text | Single-base resolution of mouse offspring brain methylome reveals epigenome modifications caused by gestational folic acid

Background

Epigenetic modifications, such as cytosine methylation in CpG-rich regions, regulate
multiple functions in mammalian development. Maternal nutrients affecting one-carbon
metabolism during gestation can exert long-term effects on the health of the progeny.
Using C57BL/6 J mice, we investigated whether the amount of ingested maternal folic
acid (FA) during gestation impacted DNA methylation in the offspring’s cerebral hemispheres.
Reduced representation bisulfite sequencing at single-base resolution was performed
to analyze genome-wide DNA methylation profiles.

Results

We identified widespread differences in the methylation patterns of CpG and non-CpG
sites of key developmental genes, including imprinted and candidate autism susceptibility
genes (P <0.05). Such differential methylation of the CpG and non-CpG sites may use different
mechanisms to alter gene expressions. Quantitative real time reverse transcription-polymerase
chain reaction confirmed altered expression of several genes.

Conclusions

These finding demonstrate that high maternal FA during gestation induces substantial
alteration in methylation pattern and gene expression of several genes in the cerebral
hemispheres of the offspring, and such changes may influence the overall development.
Our findings provide a foundation for future studies to explore the influence of gestational
FA on genetic/epigenetic susceptibility to altered development and disease in offspring.

Related articles

• New Evidence For Epigenetic Effects Of Diet In Healthy Ageing (medicalnewstoday.com)
• Diet May Induce Epigenetic Changes In Women Before Pregnancy That Are Inherited By Offspring (medicalnewstoday.com)
• Epigenetic changes in sperm of older fathers may lead to autism and schizophrenia in offspring (medicalnewstoday.com)

Breakthrough Study Shows Benefits Of Adjunctive L-Methylfolate In The Treatment Of SSRI-Resistant Major Depressive Disorder

MNT: "New research shows that patients with SSRI-resistant depression can benefit from augmentation therapy with the medical food L-methylfolate. The study, published in the American Journal of Psychiatry, demonstrates the safety superior response and tolerability of L-methylfolate, (available by prescription in the U.S. under the brand name Deplin®) in patients with Major Depressive Disorder (MDD). Approximately two thirds of people living with depression will be unsuccessful with their first round of antidepressant monotherapy. Yet, many are unaware that certain metabolic imbalances inhibit adequate response to treatment with traditional serotonin reuptake inhibitors (SSRI's) alone. "

Folic acid lowers risk of autism, study finds

 "Women who take a vitamin B9 supplement (folic acid) during the beginning weeks of their pregnancy can cut the risk of having a child with autism in half. But the supplement has no effect if it is started more than 8 weeks into the pregnancy."

Molecular Psychiatry : Cerebral folate receptor autoantibodies in autism spectrum disorder

Cerebral folate deficiency (CFD) syndrome is a neurodevelopmental disorder typically caused by folate receptor autoantibodies (FRAs) that interfere with folate transport across the blood–brain barrier. Autism spectrum disorders (ASDs) and improvements in ASD symptoms with leucovorin (folinic acid) treatment have been reported in some children with CFD. In children with ASD, the prevalence of FRAs and the response to leucovorin in FRA-positive children has not been systematically investigated. In this study, serum FRA concentrations were measured in 93 children with ASD and a high prevalence (75.3%) of FRAs was found. In 16 children, the concentration of blocking FRA significantly correlated with cerebrospinal fluid 5-methyltetrahydrofolate concentrations, which were below the normative mean in every case. Children with FRAs were treated with oral leucovorin calcium (2 mg kg⁻¹ per day; maximum 50 mg per day). Treatment response was measured and compared with a wait-list control group. Compared with controls, significantly higher improvement ratings were observed in treated children over a mean period of 4 months in verbal communication, receptive and expressive language, attention and stereotypical behavior. Approximately one-third of treated children demonstrated moderate to much improvement. The incidence of adverse effects was low. This study suggests that FRAs may be important in ASD and that FRA-positive children with ASD may benefit from leucovorin calcium treatment. Given these results, empirical treatment with leucovorin calcium may be a reasonable and non-invasive approach in FRA-positive children with ASD. Additional studies of folate receptor autoimmunity and leucovorin calcium treatment in children with ASD are warranted.

JAMA | Association Between Maternal Use of Folic Acid Supplements and Risk of Autism Spectrum Disorders in ChildrenMaternal Folic Acid Supplements and Autism

 Prenatal folic acid supplements reduce the risk of neural tube defects in children, but it has not been determined whether they protect against other neurodevelopmental disorders.

Objective  To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder–not otherwise specified [PDD-NOS]) in children.

Design, Setting, and Patients  The study sample of 85 176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity.

Main Outcome Measure  Specialist-confirmed diagnosis of ASDs.

Results  At the end of follow-up, 270 children in the study sample had been diagnosed with ASDs: 114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS. In children whose mothers took folic acid, 0.10% (64/61 042) had autistic disorder, compared with 0.21% (50/24 134) in those unexposed to folic acid. The adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90). No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use.

Conclusions and Relevance  Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation.

Folic acid intake associated with reduced risk of autism: study

(Medical Xpress) -- A new study by researchers at the UC Davis MIND Institute suggests that women who consume the recommended daily dosage of folic acid, the synthetic form of folate or vitamin B-9, during the first month of pregnancy may have a reduced risk of having a child with autism.

Depression: Have You Had Your Folate (Folic Acid) Levels Checked?

Research has long shown an association between low folate levels and depression, particularly depression that’s more severe and less responsive to medical treatment. (Folate is a water-soluble B vitamin in its natural form. Folic acid is the synthetic version found in supplements.)

Genetic variation increases risk of metabolic side effects in children on some antipsychotics

The variant was in MTHFR (methylenetetrahydrofolate reductase)