One in 68 Children has Autism
The past few years have seen advances in our understanding of genetic and epigenetic basis of autism spectrum disorder. Epigenetic regulation refers to the study of heritable changes in gene expression that do not involve changes in the DNA sequence (van Vlietv, et al. 2007). These are changes that, for instance, can regulate which genes can be turned “on” and which are turned “off.” According to Sweatt (2009), epigenetics can explain the biologic puzzle in a person’s body of how different cells can have the exact same DNA but different gene expression. In other words, epigenetics can help explain how a muscle cell and a fat cell can have the same DNA, but function completely different.
A number of neuropsychiatric disorders and phenotypes have been associated to epigenetic variations such as Rett syndrome (caused by mutations in the transcriptional repressor MECP2), Fragile X syndrome (FXS – Mutations in the FMR1), Angelman syndrome (loss of function of a gene called UBE3A) and Prader-Willi syndrome (loss of genes in a specific region of chromosome 15), depression, schizophrenia, and addiction (Tsankova, et al. 2007). Epigenetic may help to understand how identical twins with the exact same DNA can have one member with autism or schizophrenia and the other not. Theoretically, the abnormal gene is silenced in the normal twin but activated in the twin with autism or schizophrenia. (Stahl, 2008, Nestler, 2009, Abdolmaleky, et al. 2008, 2004).
Methylation of DNA not only serves to mediate repression of gene expression in imprinted domains, but also provides a mechanism through which environmental factors can have long-lasting effects on the genome. Methylation is an epigenetic event that affects cell function by altering gene expression. During Methylation, methyl groups are transferred from the cofactor, S-adenosyl-L-methionine, to the fifth-carbon of cytosine in a Cytosine-phosphate-Guanine dinucleotide. This reaction is catalyzed by one of the DNA methyltransferase enzymes. DNA Methylation is an epigenetic event that affects cell function by altering gene expression. (Schanen, 2006).
Several studies have demonstrated some abnormalities in the metabolic functioning of children with autism with defects or significantly lower baseline plasma concentrations of methionine, S-adenosylmethionine (SAMe), homocysteine, cystathionine, cysteine, and total glutathione and significantly higher concentrations of S-adenosylhomocysteine (SAH), adenosine, and oxidized glutathione (James, 2004; Levitt, 2005). This metabolic profile is consistent with impaired capacity for Methylation (significantly lower ratio of SAMe to SAH) and increased oxidative stress, which refers to the presence of any of a number of reactive oxygen species (ROS) which the cell is unable to counterbalance. The result is damage to one or more biomolecules including DNA, RNA, proteins and lipids (Ming X, et al. 2008).
Autism is a complex neurodevelopmental disorder whose cause is unknown and which is diagnosed solely on behavioral criteria (Lord, et al. 2000). The incidence of autism has been increasing and is now thought to be present in ~1 in 110 children in the United States (CDC, 2009). There is a hypothesis that autism may be caused by a lack of methyl donors that impairs the process of Methylation during critical points in the early development process. However, there are too many things that can cause a shortage of methyl donors in the body, the two leading are toxins and poor nutrition and defective adulterated food. S-adenosyl-L-methionine could be a fast and effective means of countering methyl donor shortages (Gerber, 2009).
S-Adenosylmethionine (SAMe) is a compound found in all living cells that is involved in essential methyl group transfers. S-adenosyl-L-methionine (SAMe) is the most important methyl donor in the brain and is essential for polyamine synthesis. Methyl group deficiency in the brain has been implicated in depression. It is the principal methyl donor in the one-carbon cycle, with SAMe levels depending on levels of the vitamins, folate and B12. SAMe is involved in the Methylation of neurotransmitters (norepinephrine, serotonin, and dopamine), nucleic acids, proteins, hormones, and phospholipids (Mischoulon & Nierenberg, 2004; Mischoulon & Fava, 2002; Spillmann & Fava, 1996).
There are evidence-based studies that show SAM-e as being superior to placebo and equivalent to the Tricyclic antidepressants [e.g. Imipramine / Tofranil] and Citalopram [Celexa] and Escitalopram (Lexapro) (SSRI antidepressants) in efficacy as monotherapy for patients with mood disorders (Fava, 2007, 2004; Spillmann & Fava,1996; Benelli, Filaferro, Bertolini & Genedani, 1999).
Research studies suggested that some children with autism spectrum disorder have abnormalities in the brain system that makes serotonin, which plays an important role in early brain development. Children with obsessive compulsive disorder (OCD) and mood dysregulation disorders may also have serotonin abnormalities and have repetitive or inflexible behaviors (Archives of General Psychiatry, 2009).
Over recent decades, the use of complementary and alternative medicine (CAM) such as S-adenosyl-methionine (SAMe), Omega-3 fatty acids, Folic acid, Vitamin B12 and St. John’s Wort (all over-the-counter supplements) has increased among patients with psychiatric disorders and in the general population.
S-adenosyl-methionine (SAM-e) therefore is a natural medication that appears to be relatively safe and shows promise as an antidepressant. The epigenetic hypothesis and the impressive literature extending back three decades suggest the antidepressant efficacy of S-adenosyl-methionine (SAM-e). Perhaps some researchers may want to conduct investigations of the role of S-adenosyl-methionine (SAM-e) in autism spectrum disorders.
QSAC is a New York City and Long Island based nonprofit that supports children and adults with autism, together with their families, in achieving greater independence, realizing their future potential, and contributing to their communities in a meaningful way by offering person-centered services.
QSAC pursues this mission through direct services that provide a supportive and individualized setting for children and adults with autism to improve their communication, socialization, academic, and functional skills.