Nearly a third of youth manifest somekind of anxiety disorder by age 18, and 15 percent experience depression. Females are at greater risk than males. We know that maltreatment in childhood and other chronic life adversities account for up to a third of the risk, but the reasons for the correlation are not well understood.

Now, a new study from a team at the University of Wisconsin-Madison casts light on how negative events in childhood, including the kinds of chronic stress experienced in a community sample, may alter brain circuitry and lead to symptoms of anxiety and depression.

Ryan Herringa and his colleagues studied brain scans (prepared in Richard Davidson's lab) from 64 adolescents (30 of them female) who participated in the Wisconsin Study of Families and Work. That study has followed these youth prenatally up to (most recently) age 18. The goal of the study (led by Herringa's collaborator Marilyn Essex) has been to identify social, psychological, and biological risk factors for child and adolescent mental health problems. Experiences of adversity and maltreatment were assessed via the Childhood Trauma Questionnaire (CTQ), completed at age 18. The CTQ is a brief survey of six early traumatic experiences (death, divorce, violence, sexual abuse, illness, or other) and self-ratings of the impact of the traumas.

In this week's Proceedings of the National Academy of Sciences, the research team reports associations between life traumas in childhood, internalizing symptoms associated with depression and anxiety, and connectivity between the brain regions known as the amygdala and the hippocampus. (The hippocampus is an important node in the brain’s fear network; it helps regulate fear responses by communicating with the amygdala and the brain's higher "thinking centers" in the prefrontal cortex.)

The study demonstrates that negative childhood experiences may lead to altered connectivity in the brain’s fear circuitry—which, in turn, may lead to the development of internalizing symptoms such as depression and anxiety by late adolescence—especially in females. "Childhood maltreatment experiences may lead to poorer communication between the hippocampus and prefrontal cortex in girls and boys, but poorer communication between the amygdala and prefrontal cortex in girls only," explains Herringa. "These brain changes, in turn, are associated with the development of anxiety and depression symptoms by late adolescence (age 18)."

This finding suggests that both girls and boys develop impaired contextual regulation of fear due to poor communication between the hippocampus and prefrontal cortex. "However, girls may experience a 'double hit' following maltreatment experiences [because of] a lower ability of the prefrontal cortex to inhibit fear through its direct connections with the amygdala," says Herringa.

Researchers have repeatedly demonstrated that early life experiences are very important for the developing brain. Chronic stress and traumatic events can significantly alter brain development. Herringa thinks that changes in brain circuitry may be the brain's way of adapting to a stressful or threatening environment, but that such adaptation may come at a high price: an increased risk of mental illness.

Ryan Herringa is an assistant professor of child and adolescent psychiatry at the University of Wisconsin.

"We think it’s important to emphasize that this is a community sample, and that we examined maltreatment experiences that would generally not be considered reportable cases of abuse . . . It is therefore important for parents, teachers, and community leaders to recognize that even these lower levels of maltreatment experiences may lead to changes in the brain’s fear circuitry and put kids at risk for developing anxiety and depression.

"We believe that finding the brain mechanisms linking childhood maltreatment experiences and later anxiety and depression will be important for developing new treatments for internalizing disorders. . . . It will continue to be important for us as a society to help support caregivers in a positive parenting role, which may then have a significant impact on their children’s brains and mental health," concludes Herringa.

For More Information

Ryan J. Herringa, Rasmus M. Birn, Paula L. Ruttle, Cory A. Burghy, Diane E. Stodola, Richard J. Davidson, and Marilyn J. Essex. Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence. PNAS Online Early Edition, November 4, 2013. 

Ryan Herringa's Research Lab

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