German scientists have discovered how childhood stress genetically alters kids so that they become stressed-out adults.
They found that stress at an early age permanently alters the expression of a key gene in the brain, resulting in a lifetime of elevated levels of a hormone that contributes to depression, according to a study published in the journal Nature Neuroscience.
In the study, the team of researchers stressed out baby mice by separating them from their mothers for three hours a day during their first 10 days of life. Other mice were kept with their mothers continuously, to serve as controls.
According to a common hypothesis, the environment affects mental heath by causing alterations to the physical properties of the genome that influence gene expression - the epigenome. The new research supports that hypothesis by suggesting that DNA methylation, one of the most intensely studied forms of epigenetics, may explain why maternal care has a long-term influence on behaviour and hormones in rats.
To explore whether DNA methylation is behind the changes associated with stress experienced early in life, molecular biologists Chris Murgatroyd and Dietmar Spengler of the Max Planck Institute of Psychiatry in Germany and colleagues examined the methylation patterns of mice that were separated from their mothers for three hours a day for the first 10 days of their lives..
Specifically, the researchers looked for differences in the gene that encodes arginine vasopressin (AVP), a hormone associated with mood and cognitive behaviours. The AVP receptor is also a promising therapeutic target for stress-related disorders.
All the animals got blood tests when they were six weeks, three months and one-year-old. The mice that had been removed from their mothers’ nests had higher levels of the stress-related hormone corticosterone circulating in their blood than their counterparts, the researchers found.
When the animals were subjected to stressful situations, the traumatized mice also produced more corticosterone than the controls.
From six weeks of age all the way up to one year, mice that experienced early stress - and showed the predicted behavioural and hormonal differences - also displayed significantly lower levels of methylation in the regulatory region of the AVP gene in the brain.
This hypomethylation was specific to a subset of neurons in the hypothalamic paraventricular nucleus - a brain area involved in regulating hormones linked to stress. These mice also had higher levels of AVP mRNA, suggesting that lower methylation levels do indeed affect hormone levels.
“Our results suggest that adverse events in early life can leave persistent epigenetic marks on specific genes that may prime susceptibility to neuroendocrine and behavioural dysfunction,” the scientists concluded.