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OHSU Research Reveals Likely Connection Between Early-Life Stress And Mental Health Problems During The Teenage Years

Research to be presented Wednesday, Nov. 16, at the Society for Neuroscience Meeting in Washington, D.C. 

Research conducted at the Oregon National Primate Research Center at Oregon Health & Science University and at the University of Pittsburgh suggests a strong link between significant stress early in life and the increased incidence of mental health problems during adolescence. The research strengthens the case for proactive treatment or counseling of children who undergo a significant early-life stress. The research is being presented during the Society for Neuroscience meeting in Washington, D.C., Nov. 12-16. The meeting is one of the largest and most respected gatherings of neuroscientists in the world.

Both past research and human observation reveal that children who experience early-life stresses such as abuse, neglect, or loss of a parent have an increased risk of developing attachment disorders. Later in childhood, these same children show an increased incidence of manifesting some types of  behavioral and emotional disorders, including attention deficit/hyperactivity disorder, conduct disorders, anxiety, depression, suicide, drug abuse and post-traumatic stress disorder. Both genetic factors and life experiences appear to play a role in the causes of these mental health disorders.

"Until now only human observation and theories have suggested that early-life stresses can also lead to problems as far away as the teenage years," said Judy Cameron, Ph.D., a senior scientist in the divisions of Reproductive Sciences and Neuroscience at the OHSU Oregon National Primate Research Center. Cameron also is a professor of psychiatry at the University of Pittsburgh. "By studying a species that has responses to early-life stresses that are very similar to young children, we can get a developmental picture that is much clearer than in humans."
Interpretation of human epidemiological studies are often difficult because children experiencing early-life stresses frequently have exposure to many other situations, such as ongoing mental or physical abuse or neglect,  both of which can increase the incidence of mental health problems. In contrast, for this study researchers were able to rear rhesus macaque monkeys with a one-time stress exposure, followed by rearing in a very stable social environment. The findings provide strong evidence that stress exposure early in life can have dramatic, long-lasting effects that persist into the teenage years and perhaps even adulthood, even in the face of an otherwise stable rearing, such as would be recommended for children experiencing early life stresses. 

"Some of the most important clinical questions targeting early intervention for behavioral and emotional problems in youth will require a deeper understanding of the unique vulnerabilities linked to neural changes at puberty and adolescence - and more specifically, how these adolescent changes interact with earlier vulnerabilities such as major life stressors and social adversity early in life," said Ronald E. Dahl, M.D., the Staunton Professor of Psychiatry and Pediatrics at the University of Pittsburgh. "This line of study by the Cameron lab is providing unique insights into these developmental interactions in ways that can not be achieved in controlled studies in humans."

The researchers studied 16 small social groups of monkeys for a three year period. Because monkeys mature at a much more accelerated pace than humans, a monkey 2 to 4 years old would correspond to a human teenager in regard to mental and physical development. To ascertain the impacts of an early-life stress, certain monkeys had their mothers removed from the social group at various stages early in life. These monkeys continued to be raised in the stable social groups with other monkeys - similar to a human child that loses a parent but continues to be raised in their family. Some infant monkeys had their mothers removed from the social group when they were 1 week old. These infants went on to be alert and active, but to show less than normal interest in social interactions. Their behavior looked similar to children who develop a form of attachment disorder characterized by withdrawal from social interactions. Some infant monkeys had their mothers removed from the social group when they were 1 month old. These infants went on to show increased clinginess and seek social comfort more than normal. Their behavior looked similar to children who develop a form of attachment disorder characterized by indiscriminate clinginess.
In adolescence, one-week separated monkeys continued to spend less time in social contact with other monkeys, and showed more time displaying self-comforting behaviors, such as snuggling a toy or even sucking their thumb, especially when they were placed in mildly stressful situations. In adolescence they also showed less inclination to explore novel, interesting situations - this has been taken as a marker of anxiety in human studies. In contrast, adolescent monkeys who had experienced maternal separation at 1 month old continued to show significantly more time in social contact compared to monkeys not experiencing the stress of early maternal separation. However, they also developed several new behavioral characteristics in adolescence. Like one-week separated monkeys they, too, developed a reduced inclination to explore novel, interesting situations. And, they also developed "freezing" behavior in response to fearful stimuli - again a characteristic of increased anxiety in humans.

"Why there is an increase in the expression of anxious behaviors in individuals experiencing early-life stress during puberty remains unknown," said Cameron. "However, we now know this occurs both in humans and in nonhuman primates. We hope that the increased ability to study behavior and pubertal development in nonhuman primates will allow us to more thoroughly address this issue. We can speculate that hormonal changes that occur with puberty interact with the neural circuits whose function is modulated by early-life stress, but identifying such potential mechanisms will take further work. We are encouraged that the nonhuman primate model will allow this type of study."

Another issue that has been raised in clinical studies of children experiencing early life stress, is whether the timing of puberty is affected by such stress exposure. Girls experiencing sexual abuse early in life have been reported to go through puberty at earlier ages than non-abused girls. However, in this report, the researchers tracked reproductive hormones and the incidence of menstrual bleeding in female monkeys throughout puberty and found that there were no differences in the timing of puberty onset in animals that had experienced early-life stress compared to control animals. This finding suggests that early puberty onset may not be a response to all types of early-life stress, but may be more specific to girls experiencing early sexual abuse.
Support for this research was contributed by the John D. & Catherine T. MacArthur Foundation.

The ONPRC is a registered research institution, inspected regularly by the United States Department of Agriculture. It operates in compliance with the Animal Welfare Act and has an assurance of regulatory compliance on file with the National Institutes of Health. The ONPRC also participates in the voluntary accreditation program overseen by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC).


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