A&O READING – STRESS by Sapolsky (2003)

EXCERPTS from “TAMING STRESS” by Robert Sapolsky (Scientific American, 2003):

“OVER THE CENTURIES,  SOCIETY’S APPROACHES  TO TREATing the mentally ill have shifted dramatically. At present,  drugs  that  manipulate neurochemistry count as cutting-edge therapeutics. A few decades ago the heights of efficacy and compassion were lobotomies and  insulin-induced comas.  Before that,  restraints and ice baths sufficed. Even earlier, and we’ve entered the realm of exorcisms.

Society has also shifted its view of the causes of mental illness. Once we got past invoking demonic possession, we put enormous energy into the debate over whether  these diseases are more about nature or nurture. Such arguments are quite pointless given the vast intertwining of the two in psychiatric  disease. Environment, in the form of trauma, can most certainly break the minds of its victims. Yet there is an undeniable biology that makes some individuals more vulnerable than others. Conversely,  genes are most certainly important factors in understanding major disorders. Yet being the identical twin of someone who suffers one of those illnesses means a roughly 50 percent chance of not succumbing.

Obviously, biological vulnerabilities and envronmiental precipitants interact,  and in this article I explore one arena of that interaction: the relation between external factors that cause stress and the biology of the mind’s response. Scientists have recently come to understand a great deal about  the role that stress plays in the two most common classes of psychiatric  disorders:  anxiety and major depression,  each of which affects close to 20 million Americans annually,  according to the National Institute  of Mental  Health.  And much investigation  focuses on developing the next generation of relevant pharmaceuticals, on finding improved versions of Prozac, Wellbutrin, Valium and Librium that would work faster, longer or with fewer side effects.

At the same time, insights about stress are opening the way for novel drug development. These different tacks are needed for the simple fact that despite laudable  progress in treating  anxiety and depression, currently available medications do not work for vast numbers  of people, or they en- tail side effects that are too severe.

Research in this area has applications well beyond  treating  and  understanding these two  illnesses. The diagnostic  boundary that  separates someone who is formally ill with an anxiety dis- order or major depression  from everyone else is somewhat arbitrary. Investigations  into stress are also teaching us about  the everyday anxiety and depression that all of us experience at times.” (2003:87)

Out of Balance

WHEN A  BODY is in homeostatic balance, various measures—such  as temperature, glucose level and so on—are as close to “ideal” as possible. A stressor is anything in the environment that knocks the body out of homeostasis, and the stress response is the array  of physiological  adaptations that  ultimately reestablishes balance. The response principally includes the secretion of two types of hormones from the adrenal  glands: epinephrine, also known  as adrenaline, and glucocorticoids. In hu- mans, the relevant glucocorticoid is called cortisol, also known as hydrocortisone.

This suite of hormonal changes is what stress is about  for the typical mammal.  It is often triggered by an acute physical challenge, such as fleeing from a predator. Epinephrine  and glucocorticoids mobi- lize energy for muscles, increase cardiovascular tone so oxygen can travel more quickly, and turn off nonessential  activities like growth.  (The hormones work at different speeds. In a fight-or-flight scenario, epinephrine is the one handing out guns; glucocorticoids are the ones drawing  up blueprints for new aircraft carriers needed for the war effort.)

Primates have it tough, however. More so than in other species, the primate  stress response can be set in motion  not only by a concrete event but by mere anticipation. When this assessment is accurate (“This is a dark, abandoned street, so I should pre- pare to run”), an anticipatory stress response can be highly adaptive. But when primates, human or otherwise, chronically  and erroneously believe that a homeostatic challenge is about  to come, they have entered the realm of neurosis, anxiety and paranoia.

In the 1950s and 1960s pioneers such as John Mason, Seymour Levine and Jay Weiss—then at the Walter Reed Army Medical Center, Stanford University and the Rockefeller University, respectively— began to identify key facets of psychological  stress. They found that such stress is exacerbated if there is no outlet for frustration, no sense of control, no social support and no impression that something bet- ter will follow. Thus, a rat will be less likely to develop an ulcer in response to a series of electric shocks if it can gnaw on a bar of wood throughout, because it has an outlet for frustration. A baboon will secrete fewer stress hormones in response to frequent fighting if the aggression results in a rise, rather than a fall, in the dominance hierarchy; he has a perception that life is improving.  A person will become less hypertensive when exposed to painfully loud noise if she believes she can press a button at any time to lower the volume; she has a sense of control.

But suppose such buffers are not available and the stress is chronic. Repeated  challenges may demand repeated  bursts of vigilance. At some point, this vigilance may become overgeneralized, leading an individual to conclude that he must always be on guard—even in the absence of the stress. And thus the realm of anxiety is entered.  Alternatively,  the chronic stress may be insurmountable, giving rise to feelings of helplessness. Again this response may be- come overgeneralized: a person may begin to feel she is always at a loss, even in circumstances that she can actually master. Depression is upon her.

Stress and Anxiety

FOR  ITS  PART , anxiety seems to wreak havoc in the limbic system, the brain region concerned with emotion.  One structure is primarily  affected: the amygdala,  which is involved in the perception  of and response to fear-evoking  stimuli. (Interestingly, the amygdala  is also central to aggression, underlining the fact that aggression can be rooted  in fear—an  observation that  can explain  much  sociopolitical behavior.)

To carry out its role in sensing threat, the amygdala receives input from neurons  in the outermost layer of the brain, the cortex, where much high-level processing takes place. Some of this input comes from parts of the cortex that process sensory information, including specialized areas that recognize individual faces, as well as from the frontal  cortex, which is involved in abstract associations. In the realm of anxiety, an example of such an association might be grouping  a gun, a hijacked plane and an anthrax-tainted envelope in the same category. The sight of a fire or a menacing face can activate the amygdala—as can a purely abstract thought.

Whether it orchestrates such powerful reimmersions or not, the amygdala is clearly implicated in certain kinds of memory. There are two general forms of memory. Declarative, or explicit, memory governs the recollection of facts, events or associations. Implicit memory has several roles as well. It includes procedural memory: recalling how to ride a bike or play a passage on the piano. And it is involved in fear. Remember the woman reacting to the similarity be- tween two voices without being aware of it. In that case, the activation of the amygdala  and the sympathetic  nervous system reflects a form of implicit memory that does not require conscious awareness.