Parents' Abusive Behavior Can Change Child's Genes

Infant abuse can alter the brain, both animal and human experiments have shown. Infant abuse may also be capable of altering genes in the human brain. Postmortem examination of the brains of people who had had a history of early childhood abuse or neglect and postmortem examination of the brains of people who had not had such a history revealed reduced gene expression in the hippocampus of the former, Patrick McGowan, Ph.D., of the Douglas Mental Health University Institute in Montreal, Canada and colleagues reported in the May 7, 2008, PLOS One.

Now researchers report something even more startling—that gene alteration caused by infant abuse can be transmitted to the next generation, at least in rodents.

The lead investigator of this new study was Tania Roth, Ph.D., a postdoctoral fellow in neurobiology at the University of Alabama at Birmingham. Results appeared in the May 1 Biological Psychiatry.

Roth and her colleagues used 14 rat pups for their first experiment. Half were exposed to a stressed, abusive mother for 30 minutes daily during the first postnatal week, and the other half to a positive caregiving mother during the first postnatal week. This means that the first group was roughly handled or actively rejected by their mothers, whereas the latter group was licked, nursed, carried around, or otherwise positively handled by their mothers.

After the rat pups became adults, the researchers conducted postmortem examinations to see whether there were any differences between the brains of the maltreated rats and the brains of the control rats as far as the expression of brain-derived neurotrophic factor (BDNF) gene was concerned. This gene makes a protein that stimulates nerve development in the brain, and it seems to be involved in a number of mental illnesses (Psychiatric News, December 7, 2007).

The researchers found changes in the methylation of the BDNF gene and in turn changes in BDNF gene expression in the prefrontal cortex of the maltreated animals but not in the control animals.

The researchers then focused on five of the female rats that had been maltreated as infants and looked to see whether they maltreated their own offspring. They did. The researchers also discovered that these offspring had the same BDNF gene methylation in the prefrontal cortex that their mothers had had. So it looks as if the female rats had not only passed maltreatment on to the next generation, but that this transmission may have been at least partially via methylation of the BDNF gene.

At first glance, it may seem rather improbable that one generation's life experiences could be transmitted to the next generation genetically. However, the experiments that Roth and her team conducted are part of an emerging field of science called epigenetics, which has shown that not just life experiences, but diet, alcohol, nicotine, and some other environmental factors can alter genes in the brain. Such alterations are often caused by methylation, in which a methyl group attaches to the control segment of a gene and either silences the gene or activates it without altering its genetic code. This was the case in the BDNF gene abnormalities that Roth and her group observed.

“Our results highlight a molecular mechanism that helps explain the far-reaching effects of child abuse and neglect on brain function and behavior,” Roth told Psychiatric News. “This offers a possible explanation for why adolescents and adults who were maltreated as children have higher rates of behavioral problems, substance abuse, and mental illnesses. Furthermore, [the results] give us a framework to help explain why children who have experienced abuse often become abusers themselves.”

The good news, however, is that it might be possible to interrupt, via development of a new medication, the molecular transmission of child abuse from one generation to another, Roth said.

In another experiment, she and her team took six rats that had been maltreated as pups and infused a DNA methylation inhibitor into their brains for a week. In a postmorten examination of the rats' brains, the researchers found that the compound had reversed BDNF gene methylation in their brains.

The study was funded by NARSAD and the Evelyn McKnight Brain Research Foundation.

An abstract of “Lasting Epigenetic Influence of Early-Life Adversity on the BDNF Gene” can be accessed at<www.journals.elsevierhealth.com/periodicals/bps> by clicking on the May 1 issue. ▪