ArticleMolecular psychiatry2013
Cerebral folate receptor autoantibodies in autism spectrum disorder.
Article in Molecular psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 118 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Leucovorin for the Treatment of Language Impairment in Children With Autism Spectrum Disorder
Early Treatment of Language Impairment in Young Children With Autism Spectrum Disorder With Leucovorin Calcium
Treatment of Social and Language Deficits With Leucovorin for Young Children With Autism
Who cites it
118 citing papers in PubMed, 2 syntheses or guidelines pooled it, 252 citations in OpenAlex.
- Unmetabolized Folic Acid: Biology, Epidemiology, and Clinical Consequences: A Systematic Review.Nutrients · 2026Pooled it
- Prenatal Folic Acid Supplements and Offspring's Autism Spectrum Disorder: A Meta-analysis and Meta-regression.Journal of autism and developmental disorders · 2022Pooled it
- A Mitochondrial Supplement Improves Function and Mitochondrial Activity in Autism: A Double-Blind Placebo-Controlled Cross-Over Trial.International journal of molecular sciences · 2025Trial
- Folinic Acid as Adjunctive Therapy in Treatment of Inappropriate Speech in Children with Autism: A Double-Blind and Placebo-Controlled Randomized Trial.Child psychiatry and human development · 2021Trial
- Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial.Molecular psychiatry · 2018Trial
- Review
- Article
- Can Leucovorin (Folinic Acid) Treat Autism Features?CNS drugs · 2026Article
- Folate Receptor Alpha (FRα) and the Developing Brain: From Molecular Function to Neurodevelopmental Outcomes.Molecular neurobiology · 2026Review
- Advancing understanding of the mechanisms of autism spectrum disorder through perinatal risk factors.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Serum and cerebral folate are normal in Down Syndrome Regression Disorder.Molecular autism · 2026Observational
- Cerebral folate deficiency, developmental difficulties in autism spectrum disorder and the role of leucovorin: a narrative review of mechanisms and clinical evidence.Drugs in context · 2026Review
- Immune profiling shows limited systemic changes in children with autism after autologous cord blood transfusion.Frontiers in immunology · 2026Article
- Maternal folate receptor alpha autoantibodies and folate levels during pregnancy in relation to autism spectrum disorder: a pilot case-control study.Frontiers in psychiatry · 2026Article
- Folate in autism neurodevelopment.Frontiers in nutrition · 2026Review
- Vitamins, Vascular Health and Disease.Nutrients · 2025Review
- Neurodevelopmental Impact of Maternal Immune Activation and Autoimmune Disorders, Environmental Toxicants and Folate Metabolism on Autism Spectrum Disorder.Current issues in molecular biology · 2025Review
- Transgenerational Effects and Heritability of Folate Receptor Alpha Autoantibodies in Autism Spectrum Disorder.International journal of molecular sciences · 2025Article
- Exploring the Association Between Glucose-6-Phosphate Dehydrogenase Deficiency and Autism Spectrum Disorder: A Narrative Review.Children (Basel, Switzerland) · 2025Review
- From Nutrient to Nanocarrier: The Multifaceted Role of Vitamin B12 in Drug Delivery.International journal of molecular sciences · 2025Review
58 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.