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Growing pains

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It has long been known that girls have a higher rate of depression and a lower tolerance for pain than boys. Now researchers at the University of Chicago are trying to identify the relationship between the two factors, at what age the distinction develops, and whether it is related to puberty and race. The goal is to help design preventive interventions for depression.

Thanks to a two-year American Recovery and Reinvestment Act grant for $153,000 funded by the National Institute of Mental Health, Kathryn Keenan, associate professor of psychiatry and behavioral neuroscience at the University, is able to further her studies aimed at identifying early warning signs of depression in girls.

The earlier the onset of a depressive disorder the more likely there will be a recurrence later in life. In fact, about 20% of females of childbearing age experience a depressive disorder. By targeting the preadolescent period and expanding the awareness of potential indications of vulnerability to depression, Keenan and her colleagues hope to have a direct impact on clinical practices. For example:

  • Higher than average complaints about physical pain from preadolescent girls could prompt pediatricians or school nurses to screen for depression;
  • Individual differences in a girl's behavioral and biological response to pain could be used to personalize pharmacologic interventions; and
  • Dissociation between behavioral and physiological response to a pain stimulus could indicate the need for specific interventions.

"The quickest way for one's research to impact clinical practice is to translate the research oneself," Keenan says. "Pending NIMH funding, we hope to start a preventive intervention for depression in preadolescent African American girls this summer [2011]. The intervention will be a direct translation of recently completed work on identifying individual differences in basic psychological processes that confer risk for depression."

Breaking new ground

Keenan's research is the first study to explore the interface between pain and depression using behavioral and biological responses to a controlled pain stimulus coupled with clinically meaningful measures of depressive symptoms in preadolescent girls.

To study response to pain, the researchers administered the "cold pressor task" to a group of 230 girls at ages ten to twelve years. These girls were asked to leave their arm in a tank of cold water as long as possible (for up to three minutes). During that time the discomfort was rated as well as duration of immersion. Maximum pain rating, time to highest pain rating and duration of immersion were used to characterize pain threshold and pain tolerance. These girls have also been assessed for depression annually since the age of nine years. Thus far, the data confirm that low threshold and tolerance to pain are prospectively associated with symptoms of depression.

The ARRA grant, which supports two researchers, is part of broader research aimed at identifying early signs of vulnerability to depression in girls. In addition to a correlation between depression and the response to pain, Keenan and her colleagues have observed links between depression and the regulation of emotion, the processing of emotions expressed by facial expressions, and emotional memory. All of these areas will be explored. Ultimately the objective is to develop profiles of clinically relevant and validated biomarkers and behavioral indicators of depression, thereby creating biosignatures of the risk for depression that will be translated into preventive interventions.

"Our work has demonstrated that reliable and valid predictors of adolescent depression are present during preadolescence," Keenan concludes. "Therefore, prevention of depression for a large number of girls and women will need to begin in childhood with strategies that are personalized."

by Greg Borzo

This award is funded under the American Recovery and Reinvestment Act of 2009, NIH Award number: 1R03MH084073-01A1. For more information on NIH's Recovery Act projects, visit

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