Childhood trauma may leave a lasting 'scar' inside brain cells, study finds

Severe stress in childhood can raise a person's risk of anxiety, depression and other mood disorders later in life. Researchers at Washington University School of Medicine in St. Louis and Princeton University say they identified a biological process that may help explain why, published Aug. 7 in the journal Neuron. Meaghan Creed, an associate professor of anesthesiology at WashU Medicine, said the work reveals what she called a physical 'scar' left by trauma inside brain cells.

The team studied mice, focusing on a brain region called the ventral tegmental area, whose neurons produce dopamine, a chemical messenger tied to rewards and adversity. Inside these neurons, DNA is wrapped around proteins called histones, like a coiled spring: tightly packed, genes stay switched off; loosened, they become easier to activate. The researchers found that early-life stress can loosen this packaging around stress-related genes, priming them to activate more easily.

In young mice exposed to stress, the scientists found elevated levels of an enzyme called SETD7 in dopamine neurons, compared with unstressed mice. SETD7 adds a chemical marker, H3K4me1, that helps loosen the DNA packaging. When researchers artificially raised SETD7 in unstressed young mice, their dopamine neurons developed a more open DNA structure as they matured, and the mice grew more anxious and less stress-tolerant as adults than mice with normal SETD7 levels.

The team then tested the opposite approach: after early-life stress, they blocked SETD7 from adding excess H3K4me1. This kept the DNA packaging more tightly closed and protected the mice from becoming unusually stress-sensitive later, even after adult stress. These mice behaved much like animals never stressed, with normal dopamine-neuron activity and typical social, exploratory behavior.

Catherine Jensen Pena, an assistant professor at the Princeton Neuroscience Institute and the study's senior author, said no treatments currently exist for what early-life stress does to the brain, partly because researchers have lacked a clear picture of which molecular mechanisms to target.