AT THE ANXIETY AND DEPRESSION CONFERENCE 2017

SAN FRANCISCO (FRONTLINE MEDICAL NEWS) – Children exposed to high levels of urban violence demonstrate accelerated cellular aging beyond their chronologic years, Vasiliki Michopoulos, PhD, reported at the annual conference of the Anxiety and Depression Association of America.

This fast-running cellular biologic clock is not a good thing. Neither is their blunted heart rate variability in response to stress, an indicator of autonomic dysfunction that constitutes a cardiovascular risk factor, she added.

“Overall, our data indicate a biologic mechanism by which early trauma exposure increases risk for adverse health outcomes in adulthood,” said Dr. Michopoulos of Emory University in Atlanta.

Accelerated cellular aging as measured by DNA methylation in blood or saliva samples has become a red hot research area. Investigators have shown that a person’s DNA methylation age, also known as epigenetic age, predicts all-cause mortality risk in later life. In adults, accelerated cellular aging as reflected in a 5-year discrepancy between DNA methylation age and chronologic age is predictive of an adjusted 16% increased mortality risk independent of social class, education level, lifestyle factors, and chronic diseases, including diabetes and cardiovascular disease ( Genome Biol. 2015 Jan 30;16:25 ).

Lifetime exposure to stress has been convincingly shown to accelerate epigenetic aging, as reflected by DNA methylation level. But, prior to Dr. Michopoulos’s study, it wasn’t known if exposure to violence during childhood influences epigenetic aging or if perhaps only later-life trauma is relevant.

To address this question, she and her coinvestigators recruited 101 African American children aged 6-11 years and their mothers. Of note, medical attention wasn’t being sought for the children. Rather, their mothers were approached regarding study participation while attending primary care clinics at Atlanta’s Grady Memorial Hospital. Children were not eligible to participate if they had been diagnosed with autism spectrum disorder, bipolar disorder, cognitive impairment, or a psychotic disorder.

The children had been exposed to a lot of violence, both witnessed and directly experienced, as reflected in their mean total score of 18.9 on the Violence Exposure Scale for Children-Revised ( VEX-R ). More than 80% of the children had witnessed an assault and 30% a murder. Stabbings, shootings, drug trafficking, and arrests were other common exposures.

One-quarter of the children showed accelerated cellular aging. They had experienced twice as much violence exposure as reflected in their VEX-R scores, compared with children whose epigenetic and chronologic ages were the same.

The children with accelerated cellular aging also demonstrated decreased heart rate variability in response to a standardized stressor, which involved a startle experience in a darkened room. Their heart rate in the stressor situation shot up on average by 17 bpm less than the children whose cellular age as measured by DNA methylation matched their chronologic age.

“Our data suggest that DNA methylation may serve as a biomarker by which to identify at-risk individuals who may benefit from interventions that decrease risk for cardiometabolic disorders in adulthood,” Dr. Michopoulos said. “It’ll be really interesting to see, as these kids grow up and develop, whether their phenotype stays static, reverses, or changes completely.”

Dr. Michopoulos reported having no financial conflicts regarding the study, conducted as part of the Grady Trauma Project ( www.gradytraumaproject.com ) with funding from the National Institute of Mental Health and Emory University and Grady Memorial Hospital, both in Atlanta.

bjancin@frontlinemedcom.com

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