Methylation, Epigenetics, and Mental Health (Premium)
William J. Walsh, PhD; Walsh Research Institute (Naperville, IL)
The new science of epigenetics has revolutionized our understanding of the brain and is providing a roadmap for development of improved treatments for clinical depression, schizophrenia, autism, ADHD, and criminal behavior. We are learning that many brain disorders result from environmental insults that cause certain genes to behave abnormally. For example, toxic exposures or nutrient imbalances can alter gene expression rates and may be the root cause of numerous mental disorders. Most epigenetics research is presently aimed at identifying advanced drugs that can normalize gene expression rates, but there is growing evidence that treatment using vitamins, minerals, and other natural substances may be equally effective. Psychiatric medications have served society well for the past 50 years, but the need for drug therapies may fade away as science advances.
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Every cell in the human body contains an identical copy of a person’s DNA which is essentially a blueprint for producing proteins. However, the protein requirements in the heart, liver, skin, and other tissues are very different. Epigenetics, which means “above genetics,” is the natural gene programing system that determines which genes are “turned on” and which are “turned off” in each area of the body. This is accomplished by chemical “bookmarks” or “marks” that are established in utero. Unfortunately, an abnormal chemical environment or toxic exposure can produce deviant bookmarks during the nine months of gestation and result in a predisposition for a mental illness. In addition, environmental insults can alter gene expression marks throughout one’s lifetime. Since deviant marks survive many cell divisions, the problem doesn’t go away. There is considerable evidence that epigenetic errors are responsible for mental breakdowns experienced in schizophrenia, the dramatic changes associated with regressive autism, and OCD.
The two most dominant bookmarks are methyl and acetyl groups that attach to DNA or to the histone proteins that serve as a support structure for the double helix. In general, methylation tends to suppress gene expression while acetylation tends to enhance expression. A person’s brain chemistry and mental health often depends on the competition between methyl and acetyl in the nuclei of brain cells. If methyl wins the war in the vicinity of a gene, the DNA will be compacted and gene expression reduced or prevented; if acetyl wins the war, the DNA uncoils from the histone support structure and expression is facilitated. The methyl source for these processes is SAMe and the source of acetyl is acetyl-CoA. However, gene expression is dominated by enzymes that promote or inhibit the addition or removal of methyl or acetyl groups, and not by the amounts of SAMe or Acetyl-CoA present.
Most forms of mental illness involve imbalanced neurotransmitter (NT) activity at synapses. For several years, researchers attempted to treat depression and other illnesses by altering the synthesis (production) of specific NTs. Eventually is became clear that the controlling factor was not the amount of NT present, but the process of reuptake in which NTs in a synapse are returned to the original brain cell. The rate of reuptake is determined by the concentration of transmembrane proteins called “transporters” that act as passageways for the returning NTs. SSRI medications work by interacting with transporters and inhibiting their function. The gene expression of transporters depends on the methyl/acetyl competition at the transporter genes. About 60 years ago, Abram Hoffer discovered that Niacin was effective in treating schizophrenia. At long last, epigenetics research has identified the mechanism for this effect. Niacin (or niacinamide) inhibits sirtuins, a class of proteins that effectively remove acetyl groups from DNA and histones. The net result is increased transporter production and reduced dopamine activity that can benefit many schizophrenics. In another example, SAMe supplements promote methylation of DNA and histones, whereas folic acid favors acetylation. SAMe and methionine are natural serotonin reuptake inhibitors, whereas folates are serotonin reuptake promoters. Copper supplements tend to decrease dopamine levels and increase norepinephrine levels. Zinc and B-6 are essential for synthesis and regulation of GABA. We may be approaching a new era in psychiatry in which advanced nutrient therapy will replace drugs as the treatment of choice for brain disorders.
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