Section IV

Chronic Stress, Hippocampal Dysfunction & Behavioral Ecology

Jared Edward Reser
Psychology Department
University of Southern California

This article will present evidence supporting the hypothesis that the selective neurodegenerative effects
of prolonged stress constitute a beneficial, neuroecological program that would have adaptively
modified behavior in mammals experiencing adverse or stressful conditions. Prolonged stress and the
accompanying hormonal responses have long been known to be closely tied with decreasing synaptic
density and hypometabolism in the hippocampus and the prefrontal frontal cortex. These changes are
interpreted here as constituting a cognitive survival program that emphasizes implicit and procedural
memory over explicit and working memory. Three complementary hypotheses are proposed 1) stress
signifies that the environment is erratic and unpredictable and that the animal should be impulsive, hasty,
spontaneous and resistant to delayed gratification; 2) stress signifies that behaviors that the animal has
recently learned may be ineffective or even maladaptive and that it should increase its reliance on
innate, instinctual behaviors over learned behaviors; and 3) stress signifies that the environment is life-
threatening and that the animal should refrain from inhibiting conditioned fears. For these reasons,
during times of stress, it may be advantageous to suppress brain regions associated with advanced
learning- the frontal lobe and hippocampus- particularly because they both put great inhibitory pressure
on defensive, instinctual and dominant responses. Humans, along with countless species of vertebrates
have been shown to make predictive adaptive responses to chronic stress in many systems including
metabolic, cardiovascular, neuroendocrine and even amygdalar systems. This article proposes that
mammals may also have a cerebrocortical response to pronounced stress that allows a transition from
explicit, late, controlled/attentional processing of information to implicit, early automatic/preattentive
processing. The cognitive “symptoms” of this transition, which are sometimes referred to as the “stress
cascade,” are disadvantageous for modern humans under stress in the workplace today, but may have
been advantageous in ancestral hunting and gathering times because they minimize extraneous
thinking, maximize exploitative foraging, facilitate attentiveness to the environment and increase efforts
to avoid potential threats. Concerns relevant to ethology, neuroecology, evolutionary medicine,
hippocampal function and paleocerebral biology are addressed and explored.

It is apparent that there are three primary ways in which the brain is reshaped by stress: 1) both transient
and prolonged stress can enhance implicit fear learning and the underlying neurobiology in the
amygdala; 2) transient or mild stress can enhance explicit knowledge learning and the underlying
neurobiology in the hippocampus; 3) prolonged or severe stress can impair explicit knowledge learning
and the underlying neurobiology in the hippocampus [Sapolsky, 2003]. The first and second neuroplastic
responses to stress have been attributed adaptive significance in the literature but the third form has
mostly eluded the attention of evolutionary biologists. Upregulation of activity in the amygdala, the threat
center of the brain, would help an animal to become more sensitive and responsive to threat and the
plastic changes made there in response to stress are thought to represent a predictive adaptive
response. Secondly, the upregulation of activity in the hippocampus and frontal lobe after very mild
stress is thought to allow the animal to think faster so that it can respond quickly and efficiently in a
stressful situation. When the stress is prolonged though something very different happens. This article
focuses on this third form of neuroplastic response to stress, the neurodegeneration in the hippocampus
and frontal lobe, and attempts to understand the phenomenon in terms of its ecological utility to both
mammals and prehistoric humans. The neurodegenerative responses to stress are characterized here
as a neuroecological program that allows failing mammals to return to innate impulses. The rationale is
that if an animal’s behavioral strategies are failing then it should be less reliant on learned behavior and
should be more reliant on genetically programmed and species specific behaviors, should strive for
cerebral/metabolic efficiency and refrain from inhibiting instinctual urges. In order to understand why
chronic stress detracts from higher order cognitive abilities we turn to the neurobiology of the stress

Perceiving stress
The stress response involves a number of interacting systems including cardiovascular, endocrine,
metabolic and neurological systems. These responses to stress are known to be important adaptations
that are integral to survival and reproductive success. Usually the stress response is activated by the
perception of a stressful stimulus. The perception of an immediate physical stressor often takes place
quickly and automatically in the amygdala whereas the perception of a delayed or abstract stressor
takes place in the cerebral cortex. Because of the quick but crude processing that takes place in the
amygdala the amygdalar route is often described as the “low road” to threat perception. The cortical
route, on the other hand, is described as the high road because of the deferred, refined and conscious
aspects of its processing. The low and more direct pathway (sensory organ to thalamus to amygdala to
hypothalamus) allows the animal to respond quickly to dangerous stimuli before they have fully identified
the stimulus or assessed the situation. The high and more circuitous pathway is far slower but because it
passes through the cortex (from the thalamus) it is informed by higher learning centers which allow
context and formal thought to bear on the response.

Quite often the cortical route serves to subdue or inhibit the amygdala’s response to stress. In the text
book example, when your visual thalamus perceives something that might be a snake it sends a
message to the amygdala which confirms the crude interpretation and activates the stress response by
signaling the hypothalamus. The high, cortical route, which is thought to take at least twice as long
(around 24 milliseconds as opposed to 12 milliseconds) takes a more thoughtful, reflective look at the
visual stimulus and if it decides that the snake is actually a coiled vine it has the ability to inhibit the
amygdala’s activity quelling the fight or flight, stress response before it gathers physiological momentum.

The amygdala, the cortex and several other areas of the brain have connections to the hypothalamus,
the brain center responsible for initiating the stress response. Even transient signals from these areas
can induce the paraventricular nucleus of the hypothalamus to secrete adrenaline and corticotropin-
releasing hormone (CRH) which act throughout the brain, especially in the hypothalamus and the locus
coeruleus. Both adrenaline and CRH affect cognition and they stimulate anxiety and fear-related
behaviors. CRH also acts on the body. It induces the upregulation of the sympathetic nervous system
(the fight or flight branch of the autonomic nervous system) by acting on the brainstem, which leads to
increased cardiac output, increased blood pressure, increased respiration and the shunting of blood
away from the digestive system. These cardiovascular changes direct more blood and nutrients to the
muscles so that the animal can respond to the stressor with speed and strength. Another physiological
effect of sympathetic nervous system output is the release of the hormone adrenaline from the adrenal
medulla which in turn increases the energy available to the muscles (by converting stores of glycogen
into free glucose). These changes, along with many others, constitute an adaptive physiological stress
response to acute danger that increases mental arousal and vigilance as well as physical power.

If the stressor lasts long enough or if the CRH levels are sufficiently high, the release of
adrenocorticotrophic hormone (ACTH) is triggered within the pituitary which induces the release of
glucocorticoids (GCs) by the adrenal cortex. Cortisol, the predominant GC in humans, mediates the
physiological response to chronic or lasting stressors by inducing a suite of effects throughout the body.
Cortisol helps to further mobilize stored energy, increase cardiovascular tone and suppress costly
anabolic projects such as growth, tissue repair, immune function, reproduction and digestion. The basic
idea is that during severe stress the animal must forgo long term enterprises and refocus all of its energy
on staying alive.

The neurodegenerative effects of stress
The bodily response to acute stress, mediated by adrenaline, as well as the response to extended
stress, mediated by cortisol increase energy use in the brain heightening both memory and processing
speed. However, when cortisol levels get sufficiently high, the opposite occurs and energy usage in the
brain can be cut drastically. After about 30 minutes of intense stress this “inverted U” relationship
becomes apparent and mental function begins to decline rapidly. In fact, if the cortisol levels are
elevated over many hours or just a few days, neurodegeneration can begin to occur in the cortex,
primarily in the hippocampus.

The hippocampus, an area within the medial temporal lobe of the brain plays the role of modulator to the
hypothalamic-pituitary-adrenal response to stress. It does this by inhibiting the actions of the
hypothalamus. The hippocampus has many cortisol receptors, is very sensitive to fluctuations in cortisol
levels and is well suited for its job of creating negative feedback for CRH release (Diorio, 2000). When
blood cortisol concentrations get sufficiently high the hippocampus sends inhibitory messages through
its neuronal projections to the hypothalamus signaling that the stress response has gone on for too long
and must be diminished. Strangely though, lasting elevations of cortisol are toxic to the hippocampus
and lead to volume reduction as well as hippocampal dysfunction. Hippocampal volume is known to
decrease in response to environmental stress in rodents, monkeys and presumably most other
mammals (Lambert & Kinsley, 2004). Decreased volume of the hippocampus lowers the ability to put
negative feedback pressure on cortisol release and this is a driving element in the lasting, autocatalytic
potentiation of stress known as the “stress cascade (Sapolsky 1996).”

Aside from its function in inhibiting the hypothalamus, the hippocampus is also crucially involved in
encoding and retrieving explicit and spatial memories. Moreover, besides reducing its ability to send
negative feedback to the hypothalamus, chronic stress is known to impair hippocampus-dependent
(explicit) memory [Sapolsky et al., 1986] which is key to high-level mental functioning. As mentioned
earlier, mild or transient stress does the opposite. It acutely increases the delivery of glucose to the
brain, increasing metabolism along with memory formation and retrieval. Long term potentiation (LTP),
an important cellular facet of learning, is facilitated by very mild levels of glucocorticoids yet it is
disrupted by higher levels. Ron de Kloet discovered why this inverse-U relationship between stress and
explicit memory exists. It turns out that the hippocampus has two types of receptors that lead to two
different responses to glucocorticoid levels. The high affinity mineralocorticoid receptors for
glucocorticoids, when activated, act to enhance learning and LTP whereas the low affinity glucocorticoid
receptors (which are 10 times more difficult to bind to and are only occupied heavily during major
stressors) strongly inhibit both LTP and primed burst potentiation (PBP). When these low affinity
glucocorticoid receptors are activated heavily their occupancy leads to prolonged opening of calcium
dependent potassium channels resulting in decreased neuronal excitability and a cascade of molecular
insults. Prolonged GC elevations have been shown to lead to excitotoxicity, cytoarchitectural damage,
the inhibition of neurogenesis and atrophy of dendritic branch points in the CA1 and CA3 cell fields of
the hippocampus [Sapolsky, 2003]. Other areas of the brain are not insulted in this way, why the

The hippocampus has been relegated two different roles by evolution that are not, at first glance, easy to
reconcile. It moderates the HPA stress system as well as the explicit memory system and its ability to
function in both of its roles is impaired by stress. The damage to the hippocampus can progress to the
point of neuron loss both in humans and across mammalian species. This wide taxonomic susceptibility
makes the hippocampal neurodegenerative response to stress appear to be adaptive or evolutionarily
mediated. Perhaps continued stress sends a message telling the body that because the environment is
so stressful the animal should stop inhibiting the stress response. But why would the hippocampus be
suitable for having the function of putting negative feedback on the stress response as well as housing
the machinery to mediate explicit memory and why would both share the susceptibility to

Adverse environments call for desperate measures
Robert Sapolsky, a leading researcher on the issues of stress and neuronal degeneration, has
concluded that the stress cascade allows the brain to put emphasis on the reflexive brain regions, such
as the basal ganglia, which is responsible for reflexive movement and procedural memories (1994). To
quote the author:

“the decreased glucose delivery to (higher) brain regions like the hippocampus and cortex may be a
means to divert energy to more reflexive brain regions.”

As mentioned above, one of the hallmarks of the stress response is the rapid mobilization of energy
from storage sites, glucose from the muscles and liver, lipids from fat cells and proteins from other
tissues. This is all done in order to feed the muscles that the animal is using to save itself. Most
vertebrates, under times of severe or chronic stress, are going to be using their muscles heavily. Given
this it makes sense that after a while the higher brain areas might be turned down and all of the areas
responsible for reflexes, coordination and the learning of movement would be turned up.

Brain areas essential for vital functions, waking activity, emotion and sensory and motor activity do not
show substantial neuron loss with stress, however, the phylogenetically newer areas thought to allow
humans the patience and analytical ability to engage in cognitively rigorous foraging activities, the
hippocampus and the frontal lobes, are adversely affected.  This selective loss, may suggest that
individuals under great stress in the ancestral environment may have occupied a less cognitively
rigorous ecological niches. Like the food caching animals described above, stressed humans may have
utilized foraging strategies that were less physically and mentally demanding than the sophisticated tool-
driven hunting and complex food extraction/preparation techniques that are implemented by
contemporary hunter-gatherers.

Glucocorticoids generally cause different tissues and organ systems to put off long-term, expensive
building projects like growth, most forms of anabolism, digestion, tissue repair, sexual reproduction and
immune function. They do this to redirect the body’s efforts and energy toward fighting and flight. In much
the same way hippocampal dependent learning (unlike amygdalar learning) is very much a slow and
accumulating process that represents a long term effort at informing behavior in the distant future. It
makes some sense that if supply lines toward provident but expensive and long term projects are cut off
that the hippocampus would fall into this group. It makes sense that an animal would try to destroy ability
in the hippocampus because it holds day to day memories, where the cerebral cortex holds memories
that have been tried and true, and it took up to 2 years for the memories to consolidate there.

Behavioral strategies based on hippocampal learning can reduce stressors in a predictable and
ordered environment. This relationship probably drove the phylogenetic growth of the hippocampus,
where mammals found that they were able to systemize and understand safe places… whereas chaotic
and violent environments are not amenable to hippocampal based strategies.

If the neurological responses to profound stress and exposure to copious amounts of stress hormones
only involved neurodegeneration, then the changes might appear to be maladaptive and not intentional
or programmed. In fact, the threat center of the brain, the amygdala, literally flourishes during stress. The
amygdala has been shown to exhibit neuroplasticity and growth when exposed to high levels of GCs.
The growth of both dendrites and spines have been shown to increase in the amygdala during
chronically elevated levels of cortiol (Radley & Morrison, 2005). As mentioned before, the amygdala is a
limbic structure that is responsible for the automatic identification of threatening and emotionally laden
stimuli. Cell growth or hypertrophy in the amygdala, which is thought to be responsible for increasing
stress reactivity, can be programmed in rats through stress [Francis et al., 1999].  This selective
regulation that favors amygdala input is consistent with our conceptualization of the stress cascade as a
vigilance/fear based cognitive strategy.

Adverse environments, stress, thought and ecology

The discipline of behavioral ecology is based on the premise that cognitive traits and the neural
substrates responsible for them are shaped by natural selection and hence are fine tuned to respond to
the traditional environment of the species in question. A newer discipline called neuroecology attempts
to draw causal links from variations in brain structure between species to the lifestyle of these species.
For instance, a species that forages over wide terrain or hides (caches) food more than a similar
species would be expected to have a larger hippocampus because the hippocampus, an area
responsible for spatial cognition, plays a bigger role in its ecological behavior. Neuroecology has
received some criticism because the predictions that it tests are largely adaptationist and thus can
provide only limited insight into the underlying mechanisms. The creation of the present hypothesis was
also driven by adaptationist logic (i.e. if it exists it must have been naturally selected) but unlike the
observations in neuroecology this research has a serious emphasis on convergent evidence and
comparative substantiation.

The phenotypic characteristics of many organisms ranging from plants to insects to mammals are
known to show plastic responses to environmental events, many of which are thought to represent
adaptive, defensive responses or reproductive strategies (Via & Lande 1985; Fox & Mousseau). The
epigenetic, neuroplastic changes that cause the stress cascade may be an example of a predictive
adaptive response. In fact, neuronal degeneration in the hippocampus is known to occur in a wide
variety of birds and mammals in response to environmental cues and this neurodegeneration has been
attributed adaptive significance [Clayton, 2001]. Hippocampal neuron number fluctuates in individual
animals and these fluctuations correlate with ecologically salient, environmental circumstances.
Ethological research has shown that in both birds (Garamszegi & Eens 2004) and mammals
(Kemperman 2002) neurodegeneration can be a programmed, adaptive response to environmental
concerns. In fact, neurogenesis in the hippocampi of individual adult mammals is known to increase with
environmental stimulation and enrichment (Kemperman 1997; 1998) and decrease along with the
diminishment of body size, metabolic rate and need to forage (Jacobs, 1996).  This relationship,
between environmental demands and investment in hippocampal neurons is commonly interpreted to be
an ecological strategy (Dukas, 2004).

Other neurobehavioral anomalies present in stressed mammals from rats to humans. Sensory gating
deficiencies, specifically, prepulse inhibition and habituation deficits can be induced in several
mammals through chronic stress. Restraining the legs of rat or mouse for very brief periods, exposing
them to the scent of a natural predator and exposing them to a dominant individual of their species are
some of the most widely used and reliable ways to increase blood plasma levels of GCs. Keeping these
levels elevated for days results in habituation deficits. Habituation is an automatic, non-associative
learning mechanism that allows an animal to ignore (or “gate out”) extraneous stimuli.  Individuals that
have experienced severe stress show large deficits in the ability to habituate to sensory stimulation.  The
habituation deficits cause individuals to be hypersensitive to environmental stimuli, and to be unable to
regulate reflexive, automatic responses using normal inhibitory mechanisms [Lambert & Kinsley, 2004].  
This vulnerability to external stimulation causes them to be “hypervigilant” and inclined to respond to
extraneous environmental stimuli that most people are able to ignore [Venables, 1964].  This may have
served as an apt survival strategy because in a stressful world with uncontrollable variables an individual
is less likely to be able to accurately determine, on their own, which elements of their sensory
experience to attend to.   

The behavior of prepulse inhibition deficient rodents is similar to that of reptiles in that it is marked by
stereotypy- a smaller behavioral repertoire that features only the essential responses.  Similarly, stress
dementia may represent a phylogenetic step toward the past where the limbic system and other lower
brain systems are emphasized resulting in less methodical but pertinent and primal behavior. In other
words, this deficit in habituation, despite the fact that it fragments attentive concentration, may keep
highly stressed individuals from inhibiting instinctual responses to salient sensory stimuli- requiring that
they react to the important aspects of their environment.  Conversely, it seems that a very high degree of
habituation might cause an individual to gate out too much environmental information causing it to
become oblivious to important sensory stimuli.  Perhaps the adaptive value of habituation used by an
organism may vary with specific environmental variables and may involve a trade-off.  

Perhaps the damage caused by the stress cascade is a change toward a more closed learning system
that forces the human animal to slow the constant process of memory encoding and behavioral
modification. It is as if highly stressed individuals come back from conceptual journeys to their physical
senses all too quickly. Moreover, it becomes progressively harder to hold concepts in working memory,
making systematic thinking or prolonged analysis difficult.  Loss of the ability for analytical reasoning, the
ability to explicitly recall very recent thoughts, and the ability to maintain prolonged activation in a brain
area priming a specific engram are losses that seem maladaptive, until you consider the fact that these
changes make humans more like the rest of the animal kingdom. An extremely low capacity for
declarative memory, fluid intelligence and concentration does not hinder the reproductive success of
“survival machines” like worms, fish, amphibians or reptiles. Low capacity for these abilities may actually
be beneficial because it allows the animal to continuously return to its senses without being pulled out of
its element by its own thoughts – as if investing in your inner world can detract from investments in your
outer world.

If natural selection could accomplish it, it probably would have given humans all the connections needed
at birth to live, eat and procreate like it does in very simple invertebrates. Many animals that inhabit
simple ecological niches have very simple nervous systems and come into the world with nearly all of the
behavior needed preprogrammed into their bodies by their genes. These animals can only learn very
rudimentary things that only slightly modify their innate systems. Our ecological niche is so variable, on
the other hand, that our genes “know” that they could not prepare us properly by preprogramming all of
our behavior. We require a tremendous capacity to learn and integrate because it is so difficult to
predict which skill sets we will need in order to become successful foragers. Stress increases the level
of unpredictability.  Because adult humans have become programmed for survival, they are only
hindered by the ability to modify preexisting behavioral networks in the same way that a very simple
vertebrate would be at birth.  The ecological learning strategy of someone experiencing cognitive
decline due to stress seems foreign and disadvantageous until we realize how similar it is to the
learning strategies employed by simpler animals. In other words, a safe environment that sends clear,
honest signals about how to act allows animals the knowledge base to begin to formulate meaningful
theories from general experience and allows them to predict the probability of events themselves with
minimized guidance from gene imposed probability prediction (instincts).  Whereas, cognitive simplicity
(where meme utility is low) allows genes to program and motivate the individual rather than letting an
unpredictable environment program it.  

The hippocampus and cortex inhibit stress reactivity and dampen the stress response
Chronic stress is known to initiate up-regulation of the stress (HPA) axis in rodents, primates and
humans causing the stress response to become more pronounced, and more easily triggered. The fact
that this is very consistent and replicable in different species, suggests that a chronically heightened
stress response may well benefit animals that find themselves facing adverse ecological conditions. An
up-regulated stress system is thought to enhance performance during stress provoking or life
threatening situations (Wingfield et al., 1998). Increased stress responsiveness facilitates fearfulness,
vigilance and cautiousness, all traits that would have been highly adaptive during extended periods of
dire stress (Marks and Nesse, 1994). According to Zhang et al. (2004), the up-regulated stress
response created in chronically stressed rodents pups, which lasts throughout their lifetime, may be a
predictive, adaptive response that allows the animals to attain an ecological advantage by being better
prepared to react to stress provoking stimuli.

In fact, clinical anxiety, which can be thought of as simply an exaggerated stress response in humans,
has also been attributed adaptive value in evolutionary literature (Marks & Nesse, 1994).  Stress and
anxiety increase attentiveness to the environment and cause animals to make more concerted efforts to
avoid potential threats (Nesse & Williams, 1995).  Stress potentiation has been attributed adaptive
significance in the literature and increased neuroplasticity in the amygdala seems to be responsible.
Since there is a good deal of evidence supporting the view that the hippocampus inhibits amygdalar
activity (and dampens emotions by inhibiting the hypothalamus) could the hippocampal degeneration
seen in chronic stress simply function to further facilitate stress potentiation? There is a large body of
evidence implicating the hippocampus and cerebral cortex in inhibiting stress reactivity and perhaps the
damage that is done to these areas keeps them from interfering with the stress response during dire

Joseph LeDoux has written extensively about his rodent experiments involving stress, fear conditioning
and higher order learning. He explains that there is a conflict of interests between the cortex and the
limbic system where they contradict and even inhibit one another. He emphasizes that stress can
awaken old phobias and conditioned aversions that seemed to have reached extinction in even the very
distant past. This happens, he asserts, because conditioned fears are practically never unlearned, the
engram for the association remains in the amygdale, it may no longer surface though, because it is
inhibited by the cortex. Le Doux has also shown that well-conditioned or dominant responses, as well
conditioned fears are enhanced by stress. In his book, the Emotional Brain (1998), LeDoux describes
his studies that have looked at defensive responses to electrical shocks. One set of studies played 2
similar tones for rats, one tone was paired with an aversive electrical shock and the other tone, sounded
like the first tone, but did not precede a shock. Because the two tones are so similar the emotional
system becomes mobilized after hearing either tone, but if the cortex is intact the animal can inhibit its
defensive response to the safe tone. If the auditory cortex is lesioned; however, the animal can no longer
discriminate between the tones and will become afraid and assume a defensive posture in response to
both tones, every time.

The cortex has the pompous ability to inhibit life saving, defensive responses if it deems them
unthreatening. In a stressful environment that is full of threats, the animal may not be able to rely on the
discriminations made by the cortex and should react to every seemingly threatening stimulus as if it were
a full threat. It is certainly better to overreact to a nonthreat than to underreact to a true threat.

Other studies have shown that the prefrontal cortex plays a large role in inhibiting defensive and
emotional responses. A rat presented with a loud noise and a simultaneous electrical shock to its foot
will freeze when it hears the same loud noise later. If the loud noise continues intermittently but is not
accompanied by a shock, the fear learning in the amygdala remains but is effectively inhibited by the
PFC. If the rat’s PFC is damaged though, this inhibition of the amygdala cannot take place and the fear
reactions again become potent and reliable (Morgan, 1993). It seems that the neurons in the medial
prefrontal cortex are most involved in memories for fear suppression. Destruction of the ventral medial
prefrontal cortex abolishes the ability to suppress fears and causes animals to react fearfully to
conditioned fears even if they are vastly reduced in intensity (Milad & Quirk, 2002). Fascinatingly, the
medial PFC is the area that is dysregulated the most in chronic stress (Radley & Morrison, 2005).

A study of 654 army soldiers by Vasterling et al., indicated that deployment to Iraq was found to be
associated with increased risk of neuropsychological compromise. The researchers found that the
stressful deployment situation was associated with deficits in sustained attention, verbal learning and
visual-spatial memory. Fascinatingly deployment was also associated with improved simple reaction
time. The researchers suggested that the heightened behavioral reactivity may represent an
evolutionarily mediated neurobiological response to stress “in preparation for life-preserving action.” To
take this further, the deficits found in these soldiers may amount to a tendency for impaired cortical
inhibition. This may have served to help stressed ancestral individuals, during periods of adversity, react
without the normal inhibitory pressures on their reflexes and natural instincts. Behavioral disinhibition
may also have permitted stressed individuals to react without deliberately reflecting on their decisions,
helping them to escape harm and attain resources quickly and without hesitation.

The Stress Cascade and Evolutionary Medicine
Evolutionary medicine is a relatively successful and esteemed discipline that attempts to understand
disorder and disease in terms of evolutionary biology. It has clarified the evolutionary origins of many of
the most insidious diseases known. Following the pioneering work of Panksepp there has been a
movement to understand psychiatric disturbances in terms of the underlying evolutionary mechanisms
that they may represent. Many articles have analyzed various forms of psychopathology in terms of
evolutionary theory and evolutionary medicine (Baron-Cohen, 1997), and this area of research can be
referred to as “evolutionary psychopathology.”

Stress and anxiety have been seen, by researchers in the field of evolutionary medicine, to be adaptive
when they allow animals to effectively escape danger. It has been shown that animals that have a
genetic susceptibility to being highly stressed or anxious are more likely to avoid being eaten by larger
predators (Dugatkin, 1992).  In fact, Williams and Nesse (1998) have pointed out that a proclivity for
enhanced stress responsiveness may be highly beneficial in terms of reproductive success. It is widely
accepted that diverse animal species use the neuroendocrine stress axis to integrate sensory input
regarding habitat quality to inform the level of withdrawal, avoidance, paranoia and other fear related
beahviors (Meaney et al., 2000).

Articles written in evolutionary medicine have examined clinical syndromes such as anxiety, PTSD and
depression and characterized them as beneficial responses to dangers such as predator pressure and
conspecific conflict (Baron-Cohen, 1997). Some psychological and psychiatric disorders seem to
represent syndromes that are accompanied by suites of psychophysiological abnormalities that are
adaptive, when taken together, in particular environmental contexts. Many “behavioral syndromes” have
been discovered in different animal species. It is an emerging consensus now in ethology that when
traits are correlated they should be studied together as an ecological package rather than as isolated
units. The three major components of the stress cascade, cortisol dysregualtion, reduced hippocampal
volume and impairment in hippocamupus-dependent memory are also major components of
schizophrenia [Corcoran et al., 2001].  Schizophrenia, PTSD, anxiety disorders and depression are all
linked with prolonged stress, traumatic experience, elevated cortisol levels through life, exaggerated
stress response, decreased hippocampal volume, impairment in hippocamupus-dependent memory,
attentional deficits, startle potentiation, accelerated resting heart rate and increased HR responsivity
(Corcoran 2001; Axelson et al., 1993). Zhang et al, emphasize that in animals, a fundamental reliance
on stress is part of an ecological strategy that allows deprived rats rapid access to energy stores in
order to react to potential threats. Disorders like schizophrenia, PTSD, anxiety and depression could
also be related to such a “defense-adapted” phenotype. Today excessive stress impairs our ability to
function and decreases quality of life in the workplace and at home despite the fact that our stressors
are not physical or life threatening. Most evolutionary perspectives on disease, see the disease as an
adaptation that no longer helps because of differences between the ancestral environment and the
modern environment. Modern stressors rarely require physical exertion or emotional rewiring, and for
this reason, the stress cascade appears to be yet another example of an ecological anachronism.

As brain to body ratio and encephalization have increased in the animal kingdom, over the last 700
million years, many species have been granted increasing autonomy over their own behavior. The
simplest organisms, in contrast, respond in reflexive and instinctive ways that are only minimally rewired
and reconfigured by learning. More intelligent animals, like those in our phylum, chordates, have the
ability to be programmed by the environment so that the behavior of any two individuals of the same
species may be very different especially if they developed in differing environments.

When animals experience success in their natural environment, innate modules ensure that they are
rewarded chemically, and this facilitates the learning of adaptive behavior. However, if instead of
encountering success, an animal encounters stress in its environment then innate modules, like the
amygdala, act to punish or suppress the learning responsible for the maladaptive behavior. When
mammals are exposed to prolonged or severe stress, neurodegeneration in the hippocampus and
frontal lobe can result in significant modular deficits in learning and memory over time (Sapolsky et al.,
1986; 1996).

The vertebrate cortex, which is highly developed in humans, allows very high degrees of behavioral
plasticity in planned actions. Such a high degree of self-government and freedom from instinct would
potentially be very dangerous even for invertebrates because they would probably often be hard pressed
to develop adaptive behaviors on their own. A vastly increased ability for new learning probably
developed in mammals because of the presence of maternal care and maternal instruction- developing
mammals were unique because they had doting models to learn from. But what if a young mammal’s
learning does not lead to adaptive behavior? Might it be beneficial to return to instinctive behavior if
learned behavior has proven inefficacious? Such thinking may in fact explain the evolutionary logic
behind the phenomenon called “the stress cascade.”  

This article attempted to offer evidence showing that the deleterious effects of stress on learning,
memory and the hippocampus may be part of an ecological strategy to increase survival and
reproductive success. Perhaps the type of environment that induces chronic stress is not amenable to
advanced cognition. That even humans have this vulnerability says something very specific about the
place of intelligence in nature. This theory is largely underspecified due to the paucity related research
and incomplete knowledge on the part of the author. It will be interesting to see if knowledge about why
the hippocampus is plastic to stress will impact what we know about the functional roles of its
component areas.

It seems that this disucussion has resulted in three complementary hypotheses: 1) stress signifies that
the environment is erratic and adverse and that the animal should be impulsive, hasty, spontaneous and
resistant to delayed gratification and 2) stress signifies that behaviors that the animal has learned may
be inefficacious or deleterious and that it should increase its reliance on innate behaviors over learned
behaviors; and 3) stress signifies that the environment is full of threats and that the animal should not
extinguish or inhibit conditioned fears.

Where the hippocampal damage is done, is very precise and specific, I assume that the changes with
stress are very similar from person to person and species to species. Perhaps the changes are blotting
out a certain time period, or a certain memories that meet specific criteria. To understand which
memories are being suppressed and to be able to understand more about the functional neuroanatomy
of the hippocampus in this regard should tell us volumes about the place of our mind in nature.

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