Biomedical Frontiers: Winter/Spring 1996, Vol.3, No.2
Clinical Research
Early Rearing Models of Anxiety

Unpredictability in early rearing conditions in non-human primates can cause biochemical changes that are analogous to those documented in human mood and anxiety disorders in later life, according to a study by Dr. Jeremy D. Coplan. The findings have implications for the prevention and treatment of mood and anxiety disorders in clinical populations.

Following up on an animal model originally developed by primatologist Leonard A. Rosenblum of the State University of New York Health Sciences Center at Brooklyn, Dr. Coplan and colleagues have explored the neurobiology of early trauma and stress and subsequent anxiety patterns. Dr. Coplan, assistant professor in clinical psychiatry at Columbia, assistant director of the biological studies unit at NYSPI, and the study's lead author, says that the model makes it possible to experimentally exclude genetic influences on development, a strategy that is not normally feasible in humans.

VFD-variable foraging demand LFD-low foraging demand HFD-high foraging demand Each triangle and diamond represent one primate

The study looked at cerebrospinal fluid (CSF) concentrations of corticotropin-releasing factor (CRF) in primates reared during infancy by mothers confronting various foraging conditions. The mothers of the infants were randomly assigned to one of three groups: Consistently high foraging demand, in which the mothers had to dig through clean wood-chip bedding to obtain food; consistently low foraging demand, in which food was simply available on the floor of the pen; and variable food demand, which alternated between the two conditions in two-week blocks for the 12 weeks of the study. Primates in all groups received full daily rations of food. In addition, the infants had access to food and water in a separate area.

"This study suggests that disruption of early rearing and bonding has permanent chemical effects."

The study found that although CRF levels were normal in both the high-demand and low-demand groups, monkeys raised under the variable foraging conditions showed an increase in CRF levels. CRF is a pivotal regulator of the body's hormonal, immunological, physiological, and behavioral response to stress.

The CSF biochemical abnormalities were paralleled by anxious behavioral patterning depending on the stage of development. For instance, variably reared primates clung to their mothers, whereas predictably reared monkeys were apt to leave their mothers and explore a novel environment. Older variably reared primates exhibited social timidity by huddling less than primates raised in the control group.

The study also found that variably reared primates had low cortisol levels. Generally, CRF stimulates the pituitary gland to release ACTH, which in turn stimulates the release of cortisol, the major peripheral stress hormone. Therefore, high CRF levels would logically result in high cortisol. Researchers do not yet have an explanation for the low cortisol levels, though studies have found low levels in people with posttraumatic stress disorder. The study may have significant implications for the prevention and treatment of child abuse and victims of domestic violence, says Dr. Coplan. "This study suggests that disruption of early rearing and bonding has permanent chemical effects," he says. "If we understand the nature of the biochemical scars that have been left by emotional trauma, we can then design interventions that might potentially prevent these scars from becoming permanent."