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Marks of Past Experience in Schizophrenia?

January 30, 2014. In looking for the genetic roots of schizophrenia, researchers tend to focus on the sequence of letters in DNA: One letter in the wrong place could scramble the code, resulting in a malfunctioning protein that can cause trouble for the brain. But a perfectly functional gene can also be blocked by molecular additions called methyl groups. In most cases, this process of "methylation" is routine, turning genes off and on to ensure that different organs have different cells, even though they have largely the same DNA. However, methylation is also influenced by environmental factors and a person's experience. For example, stress is well known to reprogram which genes are on or off.

Researchers have been pursuing whether differences in the patterns of these methyl groups can be found in schizophrenia. A new study published online January 8 in JAMA Psychiatry looks across the entire genome for the first time. Led by Edwin van den Oord at Virginia Commonwealth University in Richmond, the study reports 25 regions that sport different patterns of methylation in 759 people with schizophrenia compared to 738 controls. These regions included genes related to hypoxia and the immune system, and the methylation patterns that exist there may reflect episodes of low oxygen or infection that occurred in the past.

Both of these findings dovetail with earlier data from epidemiology: Many studies have shown that obstetric complications or maternal infections during pregnancy slightly increase the risk of schizophrenia in offspring. In addition, genetic studies have consistently pointed a finger at genes involved in the immune system.

The study obtained this data from blood cells, which may or may not model the situation in the brain—cell types differ in part because of the different palettes of genes they express. Still, the blood-based findings may provide a useful signature of schizophrenia. A subset of the findings may actually mirror the situation in the brain and provide insights into gene regulation not usually glimpsed. (For more details, see the related news story.)—Michele Solis.

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