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Repeated exposure to unavoidable stress can lead to “learned helpless-
ness,” which can be understood as a learned sense of futility (versus control).
Learned helplessness is associated with specific brain chemical and struc-

tural alterations. For example, recent work has highlighted the importance
of downstream inhibitory control of the serotonin system in the midbrain,
over-activity of which is a key feature of learned helplessness. Specifi cally,
lesions of the rat medial prefrontal cortex cause serotonin hyperactivity and
learned helplessness behavior even when rats are given the option to control
the stressor stimulus (Amat et al., 2005). Research in this area suggests that
the prefrontal cortex plays an important role in mediating sense of control,
which in turn appears to be a critical feature of resilience to stress. In the

following section, we consider this and other findings relevant to the neuro-
biological basis of resilience to stress.

Neurochemistry of Resilience to Stress

The mediators of allostasis (e.g., cortisol and adrenalin) act in the short run to
promote adaptation to acute stress, leading, for example, to enhanced immune
defense, memory for places that are dangerous, replenishment of depleted

energy resources, and more efficient cardiovascular function (e.g., to enable

flight from danger). However, when these same mediators become over-active

or when the network of allostasis depicted in Figure 5.1 becomes dysregulated,
potentially deleterious consequences include impaired immune function,
impaired memory, increased anxiety, and other changes associated with
allostatic load (see earlier discussion). In this context, resilience can be con-
ceived as the ability to minimize allostatic load, for example, by switching off
the allostatic stress response when the stimulus threat or danger has ended.

Autonomic Nervous System Responses to Stress
The autonomic nervous system (ANS) regulates involuntary functions such

as heart rate, blood pressure, and digestion. Its two subsystems—the sympa-
thetic nervous system (SNS) and the parasympathetic nervous system (PNS)

—exert opposing effects to maintain a balance in the functioning of these
vital bodily systems. The SNS responds to stress by increasing heart rate,

constricting blood vessels, increasing blood pressure, and slowing down

digestion. However, there is significant individual variability in the extent of
these responses. Some people overreact to stress by demonstrating an unusu-

ally robust SNS response to stress. If left unchecked, persistent SNS hyper-
responsiveness can contribute to depression, chronic anxiety, posttraumatic
stress disorder (PTSD), and increased risk for a host of medical conditions,

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