This is the first epigenome-wide investigation in psychiatric research, and this groundbreaking data may be a significant step on the journey to fully understanding major psychosis.

Dr. Arturas Petronis, senior scientist in the Krembil Family Epigenetic Laboratory at the Centre for Addiction and Mental Health (CAMH), and his team studied 12,000 locations on the genome using an epigenomic profiling technology developed at CAMH. Approximately one in every two hundred of these genes showed an epigenetic difference in the brains of psychiatric patients. Significantly, these changes were noted on genes involved in neurotransmission (the exchange of chemical messages within the brain), brain development, and other processes linked to disease origins.

Dr. Petronis explains that these epigenetic changes may be the missing link in understanding what causes an illness. The DNA sequence of genes for someone with an illness like schizophrenia and a for someone without a mental illness often look the same; there are no visible changes that explain the cause of a disease. But we now have tools that show us changes in the second code, the epigenetic code, which may give us some very important clues for uncovering the mysteries of major psychosis and other complex non-Mendelian illnesses.

This proof-of-principle study is the first demonstration of what CAMH epigeneticists have hypothesized for the last 10 years. Until now, we only had theories that epigenetic changes were important to understanding what causes major psychosis, explains Dr. Petronis. Now we have the tools and expertise to support our theories and we can look at conducting larger studies, which will hopefully give us an even better understanding of psychiatric illnesses. And once we understand the primary molecular causes of an illness, we can advance diagnosis and treatment approaches, and possibly even prevent illness.

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"We discovered a clear differentiation between the metabolomic profiles of the Parkinson's disease patients versus those of the controls," Dr. Beal says. "No one molecule was definitive, but a pattern of about 160 compounds emerged that was highly specific to Parkinson's patients."

The significance of many individual compounds to the disease remains unknown and will be the focus of future study. But changes in a few well-known metabolites linked to oxidative stress were clearly linked to Parkinson's. These included low levels of the antioxidant uric acid; an increase in blood levels of another antioxidant, glutathione; and increased levels of a marker for oxidative damage called 8-OHdG.

"Together, these and other compounds were arranged into a metabolomic pattern that identified Parkinson's disease with great accuracy," Dr. Beal says.

He stressed that more work needs to be done to validate the finding, and a test that might be used routinely by doctors is still a few years away.

"We are currently enlarging the sample size and studying people at serial intervals, to see if this test might also serve as a benchmark for disease progression," Dr. Beal says. "We are also looking at people who carry a gene for a familial form of Parkinson's, but who do not have the illness now. We hope to track them over time to see if this metabolomic profile is predictive of disease onset."

If those data prove as promising as this early trial, an early-detection blood test for Parkinson's disease could someday become a reality. According to Dr. Beal, "That would be a big step forward for both the treatment and the study of this devastating illness."

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