The Biological Impact of Early Life Stress Depends on the Timing of Stress Exposure

• In Event: 2-068 - Social Origins of Developmental Risk for Mental and Physical Illnesses

Integrative Statement

We have previously published that in both male and female rhesus monkeys the timing of the early life stress (ELS) of maternal separation plays a dramatic role in determining the behavioral outcome. ELS at 1 wk of age led to dramatically lower levels of social behavior and more self-comforting behaviors than in control 6 mo separated monkeys, whereas monkeys who experienced ELS at 1 month of age showed markedly higher levels of social behavior and significantly increased social vigilance. Both groups showed increased anxious behavior in anxiety tests, with 1wk ELS monkeys showing increased self-comforting behavior and 1 mo ELS monkeys showing markedly increased vigilance and decreased exploration. Brain tissue collected at 3 mo of age show marked differences in gene expression in the amygdala of 1 wk vs. 1 mo ELS animals. However, differential changes in gene regulation between the groups were not apparent in the para-laminar nucleus of the amygdala, that develops later. Thus, ELS has differential effects on gene expression in different areas of the amygdala, reflecting specific trajectories of brain maturation at the time the stress was experienced. Four monkeys in each of 4 ELS groups (1 wk, 1 mo, 3 mo and 6 mo separated) were allowed to grow up in their stable housing condition until early adulthood (3.3-5.2 yr), and they were then regrouped into new social groups. Monkey behavior was videotaped 2x/week and temperament tests were done at 12 mo, 24 mo and 36 mo of age, as well as 2 wk after regrouping. Blood samples were collected monthly starting at 18 mo of age to track reproductive hormones. 1 wk ELS monkeys continued to show a significant decrease in social behavior (60%, p=0.016) through adolescence compared through controls, as well as significantly increased levels of self-comforting (p=0.02). In contrast, 1 mo ELS monkeys showed a significant increase in social play (p=0.028). The timing of puberty was not altered by ELS. Interestingly, when monkeys were placed in new social groups 1 wk ELS monkeys increased their social behavior to comparable levels as 1 mo ELS monkeys and 6 mo controls. Agitated behavior was increased significantly after regrouping 1 wk ELS monkeys (p=0.008) and 1 mo ELS monkeys(p=0.033), compared to controls. 1 wk ELS monkeys showed a significant increase in threat displays (p=0.007). These results indicate that even after experiencing a stable social upbringing, stressful early life experiences continue to impact behavior in adulthood in a manner specific to the timing of ELS, and these behavioral differences become more profound with stress exposure in adulthood.

Author

• Judy L Cameron, University of Pittsburgh
  Presenting Author