Epigenetic Imbalance Could Lead To Bipolar Disorder, Schizophrenia

The importance of mental health is a prominent and ongoing issue in the United States. According to the National Alliance on Mental Illness, 1 in 5 American adults experiences a mental illness in a given year, which can make living a healthy lifestyle challenging.  Some mental illnesses are due to problems with brain chemistry and are not well understood, therefore are severely under-treated.

Dopamine—one of our brain’s “feel good” chemicals— is a neurotransmitter in the brain responsible for transporting information from one neuron to another. Extreme dopamine levels are directly related to the development of different diseases: a deficiency can result in depression or Parkinson’s disease, and an abundance can lead to illnesses like bipolar disorder and schizophrenia.

Though the two are different diseases, bipolar disorder and schizophrenia share many of the same symptoms: psychosis, capricious behavior, and even hallucinations in some cases. There are some mildly effective treatments for these diseases, but none that come side-effect-free.

Previously, there haven’t been any successful ways to monitor disease progression or even any biomarkers that would show up during screenings, but according to a study from Van Andel Research Institute (VARI), we may have to turn to epigenetics in order to detect and hopefully treat the root cause of fluctuation in dopamine levels.

The study’s lead author Dr. Viviane Labrie and her team wanted to dive into the specific pathways that cause excessive dopamine production in the brain. “We’ve known since the 1970s that the effectiveness of antipsychotic medications is directly related to their ability to block dopamine signaling. However, the exact mechanism that sparks excessive dopamine in the brain and that leads to psychotic symptoms has been unclear,” Dr. Labrie said, emphasizing the importance of their research.

She and her team analyzed DNA from brain cells taken from the frontal cortex of people with either bipolar disorder or schizophrenia and compared them to healthy control cells. They found clusters of DNA methylation at a gene called IGF2, which is a crucial gene to the healthy development of synapses in the brain.

DNA methylation is an epigenetic mechanism involving the addition of methyl groups (CH3) to the 5th cytosine of DNA, which generally results in reduced gene expression. In this study, the team would find that altered DNA methylation levels would be the culprit in the development of psychosis.

These clusters were found to mix up the signaling in the brain synapses, while at the same time increasing the production of dopamine. This leads to a chemical imbalance in the brain, resulting in the unstable thought processes and other symptoms that are characteristic of bipolar disorder and schizophrenia.

They found that IGF2 also controls the production of an enzyme called tyrosine hydroxylase (TH), which regulates dopamine production. When IGF2 loses methyl groups or becomes hypomethylated, TH levels increase, resulting in an erratic production of dopamine. “What we’re seeing is a one-two punch — the brain is being flooded with too much dopamine and at the same time it is losing these critical neural connections,” Dr. Labrie said.

 “Like many other neurological disorders, schizophrenia and bipolar disorder often have early, or prodromal, phases that begin years before obvious symptoms. It is our hope that our findings may lead to new biomarkers to screen for risk, which would then allow for earlier intervention” Labrie continued, affirming the importance for future studies to help elaborate on preventative measures and treatments.

Reference: Van Andel Research Inst. “Ancient epigenetic changes silence cancer-linked genes.” May 3, 2019.

Source: Viviane Labrie, et al. Differential methylation of enhancer at IGF2 is associated with abnormal dopamine synthesis in major psychosisNature Communications 10 (2046). 2019.

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About Tim Barry 31 Articles
Tim received his B.S in Biology with minors in Chemistry and Business from DeSales University. He has been interested in epigenetics for over a decade and spent three summers researching DNA and Enzymes at Cold Spring Harbor Labs. He is impressed with how the dynamic nature of epigenetics can continually affect someone’s lifestyle and their future descendants. During his down time, Tim will be at the beach, playing golf, at the gym, or with his friends enjoying a fine glass of rye whiskey.


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