On World Health Day 2020, let’s discuss the stress response and the General Adaptation Syndrome (2/3)

The hypothalamus–pituitary–adrenal (HPA) axis acts to release cor­ti­sol into the blood stream, as cor­ti­sol calls the body into action to com­bat stress. When high amounts of cor­ti­sol inter­act with the hypo­thal­a­mus, the HPA axis will slow down its activ­i­ty. The amyg­dala detects stress, while the pre­frontal cor­tex reg­u­lates our reac­tions to stress. Source: Bezdek K and Telz­er E (2017) Have No Fear, the Brain is Here! How Your Brain Responds to Stress. Front. Young Minds. 5:71. doi: 10.3389/frym.2017.00071


[Editor’s note: Con­tin­ued from yes­ter­day’s Explor­ing the human brain and how it responds to stress (1/3)]

Stress was put on the map, so to speak, by a Hun­gar­i­an — born Cana­di­an endocri­nol­o­gist named Hans Hugo Bruno Selye (ZEL — yeh) in 1950, when he pre­sent­ed his research on rats at the annu­al con­ven­tion of the Amer­i­can Psy­cho­log­i­cal Asso­ci­a­tion. To explain the impact of stress, Selye pro­posed some­thing he called the Gen­er­al Adap­ta­tion Syn­drome (GAS), which he said had three com­po­nents. Accord­ing to Selye, when an organ­ism expe­ri­ences some nov­el or threat­en­ing stim­u­lus it responds with an alarm reac­tion. This is fol­lowed by what Selye referred to as the recov­ery or resis­tance stage, a peri­od of time dur­ing which the brain repairs itself and stores the ener­gy it will need to deal with the next stress­ful event.

He said that if the stress-caus­ing events con­tin­ue, neu­ro­log­i­cal exhaus­tion can set in. This phe­nom­e­non came to be referred to pop­u­lar­ly as burnout. It’s a state of mind char­ac­ter­ized by a loss of moti­va­tion or dri­ve and a feel­ing that you are no longer effec­tive in your work. When this men­tal exhaus­tion sets in, a per­son feels emo­tion­al­ly flat, becomes cyn­i­cal, and may dis­play a lack of respon­sive­ness to the needs of others.

What’s going on behind the scenes to cause this exhaus­tion? When humans are con­front­ed by phys­i­cal or men­tal stress or injury, an incred­i­bly com­plex and crit­i­cal­ly impor­tant phe­nom­e­non rapid­ly takes place. First to be put on alert is the hypo­thal­a­mus, which is sit­u­at­ed deep inside the brain, under the thal­a­mus and just above the brain stem. It’s only about the size of an almond, but plays a cru­cial role in link­ing the ner­vous sys­tem to the endocrine sys­tem. The hypo­thal­a­mus is par­tic­u­lar­ly inter­est­ing because it con­trols the pro­duc­tion of hor­mones that affect how the body deals with stress. When dan­ger looms, the hypo­thal­a­mus sends a near­ly instan­ta­neous chem­i­cal mes­sage down the spinal cord to the adren­al glands, which are locat­ed just above the kid­neys. This first mes­sage sig­nals the pro­duc­tion of a stress hor­mone called adren­a­line, also called epi­neph­rine, which is released into the blood stream. Nor­ep­i­neph­rine also plays a role here. The inter­ac­tion of these two hor­mones con­trols the amount of glu­cose (sug­ar) in the blood, speeds up the heart rate, and increas­es metab­o­lism and blood pres­sure, all of which get the body ready to respond to the stressor.

Mean­while, the hypo­thal­a­mus has been close­ly mon­i­tor­ing these changes, as well as the source of the stress, and now releas­es some­thing called a cor­ti­cotrophin-releas­ing hor­mone (CRH). CRH trav­els along the neu­rons that go from the hypo­thal­a­mus into the pitu­itary gland. This impor­tant gland, which is locat­ed at the base of the brain just above the roof of the mouth, releas­es some­thing called adreno­cor­ti­cotrop­ic hor­mone (ACTH) into the blood­stream. ACTH trav­els down to the adren­al glands. This trig­gers the adren­al glands to release anoth­er hor­mone called cor­ti­sol. (Seri­ous­ly, folks, isn’t this just amazing? )

Some cor­ti­sol is present in the blood­stream all the time. Nor­mal­ly, it’s present at high­er lev­els in the morn­ing and much low­er at night. Inci­den­tal­ly, recent research has found that the oppo­site is true in some chil­dren with autism, a find­ing that might shed light on this con­di­tion. A lit­tle cor­ti­sol is a good thing. It can give you that quick burst of ener­gy that comes in handy for sur­vival pur­pos­es. For a brief peri­od, it can enhance your mem­o­ry and help boost your immune sys­tem. The right amount of cor­ti­sol helps keep your body sys­tems in a healthy bal­ance, and it can fight against inflam­ma­tion and even low­er your sen­si­tiv­i­ty to pain — all good things when you’ve been injured or if you’re going into bat­tle against a sin­gle stress­ful oppo­nent. But as often hap­pens, too much of a good thing is, well … you know.

The stress response described here tem­porar­i­ly turns down or mod­i­fies nonessen­tial bod­i­ly func­tions and acti­vates the ones we need to keep us safe and healthy. It’s a won­der­ful­ly effi­cient sys­tem, and it’s fine-tuned to do its job well. Our brains and bod­ies are exquis­ite­ly designed to han­dle occa­sion­al acute stress­es or injuries. How­ev­er, they’re not well-equipped to han­dle ongo­ing or chron­ic stress.

Hans Selye’s research on the impact of stress in rats formed the foun­da­tion on which most sub­se­quent stud­ies about stress were built. Over time, and with the aid of sophis­ti­cat­ed brain imag­in­ing tech­nol­o­gy, Selye’s hypoth­e­sis has been scru­ti­nized and expand­ed. He believed that all types of stress result­ed in the same reac­tion in the brain, but we now know that this process is much more com­plex. For exam­ple, con­tem­po­rary research shows that the brain responds in dif­fer­ent ways based on its per­cep­tions of the degree of con­trol that a per­son has over a stress­ful event. Here’s how this plays out in the brain.

The more stress peo­ple are under, or feel they are under, the greater the amount of cor­ti­sol that’s pumped into the blood by the adren­al glands. If too much cor­ti­sol is pro­duced (as in acute stress) or is main­tained at high lev­els in the blood­stream for too long (as in chron­ic stress), it can be very harm­ful. This hor­mone can cause a vari­ety of phys­i­cal prob­lems, includ­ing blood sug­ar imbal­ances like hypo­glycemia (a dis­tur­bance in the func­tion­ing of the thy­roid), a decrease in mus­cle tis­sue and bone den­si­ty, and high blood pres­sure. It can make the body sus­cep­ti­ble to dis­ease by low­er­ing immu­ni­ty and inflam­ma­to­ry respons­es in the body and mak­ing it hard­er for wounds to heal. Pro­longed expo­sure to exces­sive amounts of cor­ti­sol has been impli­cat­ed in the rise of obe­si­ty because too much cor­ti­sol has been shown to be relat­ed to an increase in the amount of abdom­i­nal fat.

The Human Brain Likes to Be in Balance

For­tu­nate­ly, the brain has some built—in safe­ty sys­tems. Too much cor­ti­sol in the blood sig­nals the brain and adren­al glands to decrease cor­ti­sol pro­duc­tion. And under nor­mal con­di­tions, when the stress is over­come or brought under con­trol (by fight­ing, flee­ing, or turn­ing into an immo­bile stat­ue, or by mas­ter­ing the threat), the hypo­thal­a­mus starts send­ing out the orders to stand down. Stop pro­duc­ing cor­ti­sol!  Event over!  Under con­tin­u­ous stress, how­ev­er, this feed­back sys­tem breaks down. The hypo­thal­a­mus keeps read­ing the stress as a threat, furtive­ly send­ing mes­sages to the pitu­itary gland, which screams out to the adren­al glands to keep pump­ing out cor­ti­sol, which at this point begins to be neu­ro­tox­ic — poi­son to the brain.

Bruce Per­ry and Ron­nie Pol­lard, a well-respect­ed psy­chi­a­trist-neu­rol­o­gist team, have con­tributed much to our under­stand­ing of the impact of stress and how it affects this sense of bal­ance, or home­osta­sis, in the brain. Some­times when stress is so intense, the del­i­cate inter­ac­tion among the brain sys­tems designed to han­dle it are thrown off bal­ance. Oth­er researchers have also shown that intense, acute, or trau­mat­ic stress presents such a shock to the brain and the stress response sys­tem that it actu­al­ly reor­ga­nizes the way the brain responds to stress. For exam­ple, neu­roen­docri­nol­o­gist Bruce McEwen and neu­ro­sci­en­tist Frances Cham­pagne have shown that repeat­ed acti­va­tion of the stress response can result in phys­i­cal changes, caused by too many inflam­ma­to­ry pro­teins being pumped into the bloodstream.

Let me explain it this way: It’s rather like the keys of a piano being hit so hard that the impact puts the strings out of tune. The piano still plays, but it plays dif­fer­ent­ly. While anoth­er hard hit on the keys might have bro­ken a tuned piano wire, the now—slack wire can with­stand anoth­er hit … and anoth­er. If the hits are even hard­er, the wire stretch­es more. You can almost hear the piano (and the brain under acute stress) say­ing, “Go on, hit me again! I can take it.” But the cost is that both are out of tune and the melody is nev­er quite the same.  In the human ner­vous sys­tem, this kind of adjust­ment or adap­ta­tion pro­tects the brain from harm by chang­ing the way it responds to stress. Per­ry and Pol­lard point out that repeat­ed expo­sure to stress —chron­ic stress— results in a new way of cop­ing with a con­tin­u­ous stres­sor, but it is less effec­tive. Not a good thing.

Both repeat­ed trau­mas and chron­ic stress can result in a num­ber of bio­log­i­cal reac­tions. Neu­ro­chem­i­cal sys­tems are affect­ed that can cause a cas­cade of changes in atten­tion, impulse con­trol, sleep, and fine motor con­trol. Oth­er researchers have zeroed in on spe­cif­ic parts of the brain that are affect­ed by stress, and their work shows us just how refined and com­plex this process is. For exam­ple, Walk­er, Toufex­is, and Davis sug­gest that an area of the brain called the bed nucle­us of the stria ter­mi­nalis plays a role in cer­tain types of anx­i­ety and stress respons­es. Although this area is not thought to be involved in acute trau­mat­ic events, these authors have shown that it is respon­si­ble for pro­cess­ing the slow­er-onset, longer-last­ing respons­es that fre­quent­ly accom­pa­ny sus­tained threats. These authors fur­ther posit that the phys­i­o­log­i­cal reac­tions in this area may per­sist even after the threat goes away.

Pol­lard and Per­ry tell us that chron­ic acti­va­tion of cer­tain parts of the brain involved in the fear response, such as the hypothalamic—pituitary—adrenal (HPA) axis, can wear out oth­er parts of the brain such as the hip­pocam­pus, which is involved in cog­ni­tion and mem­o­ry. Again, cog­ni­tion and mem­o­ry: two of the most impor­tant build­ing blocks for suc­cess­ful learn­ing, atten­tion, and social communication.


–> Con­tin­ued here: The frontal lobes, the lit­tle brain down under and “Stayin’ Alive” (3/3)


Dr. Jerome (Jer­ry) Schultz is a Clin­i­cal Neu­ropsy­chol­o­gist, author and speak­er who has pro­vid­ed clin­i­cal ser­vices, con­sul­ta­tion and staff devel­op­ment to hun­dreds of pri­vate and pub­lic schools in the US and abroad dur­ing his 35-year career. This is an adapt­ed excerpt from his lat­est book Nowhere to Hide: Why Kids with ADHD & LD Hate School and What We Can Do About It, which exam­ines the role of stress in learning.


Resources to regulate stress:

Four tips to prac­tice good men­tal hygiene dur­ing the coro­n­avirus outbreak

Study finds a key ingre­di­ent in mind­ful­ness train­ing: Accep­tance (not acquiescence)

Pos­i­tive soli­tude, Feel­ing active and Future-mind­ednes: Three Keys to Well-being

New study rein­forces the impor­tance of walk­ing through forests for men­tal and gen­er­al health

Six tips to build resilience and pre­vent brain-dam­ag­ing stress

About SharpBrains

SHARPBRAINS is an independent think-tank and consulting firm providing services at the frontier of applied neuroscience, health, leadership and innovation.
SHARPBRAINS es un think-tank y consultoría independiente proporcionando servicios para la neurociencia aplicada, salud, liderazgo e innovación.

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