Page 125 - Biobehavioral Resilence to Stress

102 Biobehavioral Resilience to Stress

Developmental Influences on SNS, HPA, and Resilience

Early stress in the form of prolonged and variable postnatal maternal sepa-
ration has repeatedly been shown to promote long-term changes in brain
regions and neurotransmitter systems that have been implicated in the
pathophysiology of depression, PTSD, and resilience. For example, chronic
hyper-responsiveness of the HPA axis, the locus coeruleus/noradrenergic
system, and exaggerated emotional reactivity to stress all have been associ-
ated with prolonged and variable maternal separation (Bremner & Vermetten,
2001). It is likely that such exaggerated reactivity increases reactivity and vul-
nerability to the later development of stress-related disorders such as depres-
sion and PTSD (Kaufman, Plotsky, Nemeroff & Charney, 2000).

On the other hand, there exists a body of animal studies whose results
suggest that early exposure to mild to moderate stress that can be managed
may actually enhance the capacity to cope with stress in the future (see review
by Dienstbier, 1989). Controlled exposure to stress, as a means to enhance
resilience to stress, is known as stress inoculation. In studies of squirrel
monkeys, Parker, Buckmaster, Schatzberg, and Lyons (2004) found that stress
inoculation via brief intermittent maternal separation during postnatal weeks
17–27 led to diminished anxiety responses on subsequent exposure to a novel
environment. Stress-inoculated monkeys were also found to have lower basal
plasma ACTH and cortisol levels, and lower stress-induced cortisol levels. At
18 months of age, these monkeys were administered a response inhibition test
and were found to have superior prefrontal cortex function compared with
non-stress inoculated monkeys (Parker, Buckmaster, Justus, Schatzberg &

Lyons, 2005). These results suggest that early, mild, and controlled stress may
alter key neurobiological systems and thus serve to reduce allostatic load upon
future exposure to stress.
Rats reared in a nurturing environment have also been found to dem-
onstrate enhanced tolerance to stress in adulthood. Rat pups that receive

15 min of handling per day during the first 3 weeks of life are less reac-
tive to stress and less fearful in novel environments as adults compared

with rat pups that are not handled (Ladd, Thrivikraman, Huot & Plotsky,

2005). They also demonstrate reduced ACTH and corticosterone responses
to stress as well as a more rapid return of corticosterone levels to baseline

after exposure to stress. It appears that early environments infl uence and
shape the development of stress-related neurobiological systems with early
deprivation and uncontrollable stress promoting future exaggerated neuro-
biological stress reactivity (stress sensitization) and early nurturing or mild

to moderate stress having a positive effect on future stress reactivity (stress
inoculation). Of note, animal “adoption” studies have shown that even aft er
stress-induced neurobiological and behavioral alterations occur, it may be

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