Stress in early life can change the brain's circuitry and lead to long-term anxiety and fear of stressful situations, a new study by Weill Cornell investigators suggests.
The study, published Oct. 21 in Proceedings of the National Academy of Sciences, used mice to investigate the effect of stress early in life on the development of the amygdala, a region of the brain that helps form and store memories associated with emotional events. The mice were raised in situations that mirror the experiences of children reared in orphanages to provide insight into how such stressful upbringing can affect the human brain.
"The amygdala is involved in learning about the emotional significance of the world, especially about potentially threatening information," said Dr. B.J. Casey, director of the Sackler Institute for Developmental Psychobiology at Weill Cornell Medical College and of one of the study's co-senior authors. "Enhanced activity of this region for prolonged periods when there is no actual threat is pathological and a core feature of anxiety."
Previous studies have found that abuse, neglect or other adversity early in life is associated with emotional and behavioral problems later on, accounting for more than 30 percent of all anxiety disorders. Scientists have studied children reared in orphanages to explore how adversity affects a child's behavior, but it hasn't been clear what roles nature and nurture play in their emotional development. The disorganization and sense of neglect children experience in orphanages may account entirely for some children's later sense of anxiety and fear; other kids, however, may be genetically predisposed to psychiatric or emotional problems regardless of their early life experiences.
To account for the genetic and environmental factors that often confound studies of these children, the investigators at Weill Cornell, led by Dr. Matthew Malter Cohen, a recent neuroscience graduate student in the Sackler Institute, mimicked the experience of neglect and disorganized care of orphanage-raised children using mice. They took away some of the nesting materials from the home cage used by the mothers to hold their offspring, which caused the mothers to scamper around the cage looking for more nesting instead of licking and nursing their pups. To see how the young mice then responded to stressful situations, they were offered something they love, sweetened condensed milk, in an unfamiliar, and therefore potentially threatening, cage. The task was similar to one researchers administered to orphanage-raised children that required them to press a button when anticipating a potential threatening picture.
The researchers found that mice that had experienced the early life stress of separation were not only more cautious in approaching the bottle, they also had early and persistent changes in amygdala circuitry.
The results mirror those of an earlier study of orphaned children done by Dr. Nim Tottenham, an adjunct assistant professor of psychology in psychiatry at Weill Cornell and a co-senior author, and suggest that these children may avoid threatening situations later in life, even when those situations offer positive opportunities.
"Anxious individuals tend to avoid many opportunities that may actually be positive interactions and outcomes because they are anticipating that something bad may happen," Dr. Casey said. "Not engaging in potentially positive experiences reinforces avoidance behavior because they have nothing to counter their belief that their experiences will be negative."
This reinforcement "can lead to gradually wanting to avoid more and more things and ultimately a helplessness that can turn into later chronic depression," Dr. Casey said.
Better understanding of the effects of early-life stress may help scientists develop interventions that can mitigate, or even offset those experiences, she said.
"The team is continuing to use this approach of studying in parallel developing mice and humans to identify genetic and environmental factors that may counter the effects of early-life stress and lead to resilience," said Dr. Francis Lee, a professor and vice chair for research in the Department of Psychiatry at Weill Cornell and co-senior author. "I think the work we are doing to establish sensitive periods of emotional development when specific interventions may be most effective is the most important work we are doing."