The investigation, which appeared online this month in the American Journal of Medical Genetics, was led by the University of Georgia and involved the University of Iowa. In particular, the team found that in men and women reporting childhood abuse there are changes in the regulatory area, called the CpG island, that controls the expression of the gene that is the key regulator of serotonin and whose protein product is the primary target of most antidepressants.
A previous UI study showed that variations in this gene are linked to depression. This current study now suggests that changes to a regulatory area of the gene could separately or additionally affect the gene function.
The study, which was based on genetic data from 192 adults and their childhood recollections, was led by Steven Beach, Ph.D., director of the Institute of Behavioral Research at the University of Georgia. The investigation was based on the work of the study’s senior author Robert Philibert, M.D., Ph.D., UI professor of psychiatry, whose works focuses on molecular mechanisms that might explain gene-environmental interactions that affect mental and physical health.
“This finding is preliminary in that we might find that the association is accounted for by other, later experiences that are more common for people who have experienced child abuse, or we might find that methylation may be associated with certain facets of child maltreatment and not others” Beach said. “However, it may be that childhood maltreatment leaves a lasting mark in the form of gene methylation, and this may be important as we look for new ways to help those who have experienced childhood maltreatment, including longer-term effects.”
The study participants — 96 men and 96 women — have been ongoing participants for more than 20 years in the Iowa Adoption Studies, initiated by Remi Cadoret, M.D., a UI professor of psychiatry who died in 2005. In the new study, the team found that gene methylation was increased overall in the regulatory region of the SLC645A gene for abused males compared to non-abused males, and that for women who had experienced childhood abuse, two specific places in the gene’s regulatory region were hypermethylated.
“The effects seem to be stronger for women, and the nature of child maltreatment is often different for men and women, with sexual abuse being more common for women,” Beach said. “So we will need to continue to closely examine the gender differences in future work.”
Philibert noted that children who have been abused are much more likely to have substance abuse problems and depression.
“With child abuse, as with other health concerns, prevention is the best medicine,” he said. “This study speaks to importance of appropriate environments in which children are raised and in which we live. We see here that environmental factors affect the regulatory part of the gene, which then affects how much of the gene gets made.”
Beach noted that the small sample size of the study requires replication before firm conclusions are drawn.
“Once we replicate the basic effect, it will still be important to identify connections to specific long-term outcomes, and then this will bring us one step closer to improved prevention efforts, ” Beach said.
The study was supported by a grant from the National Institutes of Health.
The University of Iowa has filed an intellectual property claim on the CpG island, and Philibert is a potential royalty recipient.
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