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Even Happy Experiences Can't Reduce Stress


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I posted this on my blog, and Robin thought I should post it here. What do you all think?

EVEN HAPPY EXPERIENCES CAN'T REDUCE STRESS, NEW RESEARCH SHOWS </H3>This study caught my attention. It is, in itself, quite interesting. But the thing that got me was that they did this and measured these subjects' cortisol levels several times throughout the course of the interview, once beforehand, and then at 30 minute intervals. And it occurred to me: Why do sick people have to beg to get cortisol tests to check for Cushing's?!


COLUMBUS, Ohio -- Researchers here have made a surprising new discovery: They've spent the last decade examining how stressful situations can alter the levels of certain hormones in the blood, weakening the immune system and increasing a person's vulnerability to disease.


But for some people in situations typically considered stress-free -- perhaps even pleasant -- the levels of one hormone, cortisol, may even rise. Scientists have long believed that cortisol levels increase in times of stress and decrease as the stress is eased. The new finding is puzzling researchers but also pointing them to an entirely new area for future research.


The work was described August 4 by Janice Kiecolt-Glaser, professor of psychiatry and psychology at Ohio State University, at the annual meeting of the American Psychological Association in Washington, D.C.


The new work stems from a series of experiments done more than a decade ago and intended to look for physiologic changes

caused by stressful situations. A group of about 90 newlywed couples took part in the study at Ohio State's Clinical Research Center. The couples completed questionnaires and then were asked to discuss several areas of disagreement regarding their marriage.


Blood samples were taken from each subject at the beginning of the session and at 30-minute intervals until they were discharged. When researchers analyzed the data, they found changes in hormones and other bloodstream components that could indicate a weakening of the immune status.


Today's findings, however, arise from a new analysis of data from blood samples taken immediately after those "conflict" discussions. Following a short "transition" period, the newlyweds had been asked to discuss the history of their relationships - how they met, what attracted them to each other, how did they decide to marry.


"For most people, not surprisingly," explained Kiecolt-Glaser, "this was a pretty positive interaction. And they were coming down off the earlier discussion which was usually seen as a negative emotional experience."


When Kiecolt-Glaser and colleagues Ronald Glaser, professor of molecular virology, immunology and medical genetics, and William Malarkey, professor of internal medicine, looked at the levels of cortisol in the blood however, they were surprised.


"In 75 percent of the subjects, the hormone levels had fallen just as we expected - 26 percent on average for the men and 35 percent for the women," Kiecolt-Glaser said. "But in 25 percent of them, cortisol levels stayed relatively the same or, in some cases, actually went up."


Normally, levels of cortisol drop after we wake in the morning. The experiments were done in midmornings and the newlyweds were "coming down" off the negative discussion, which should have forced cortisol levels lower.


But in one of every four people in the study, the cortisol levels failed to drop. In some people, the levels even rose. The findings were especially interesting when coupled with information from follow-up surveys of the participants. The researchers had tracked down each person to check their current marital status and to find out if the newlyweds were still together.


They found that the women whose cortisol levels rose during the discussions of their relationship history were twice as likely to have been divorced from their husbands. No similar relationship appeared among men whose levels had risen.


The study also looked at the exact word choice the couples used in describing their relationship. They used an instrument called the Linguistic Inquiry and Word Count program which lists both "positive" and "negative" words - 261 which describe optimism, energy and positive feelings and 345 words suggesting anxiety, fear, sadness, depression and anger.


Cortisol levels for three-fourths of the men in the study dropped - on average 26 percent. They used significantly more words considered "positive" than did their counterparts whose cortisol remained steady or even rose. There was no similar trend in positive word choice among women whose cortisol had dropped.


Women whose cortisol levels failed to drop, or even rose, however tended to use more negative words as they discussed their relationship history. "What I think is happening here is that in some ways, cortisol levels may serve as a bellwether of what's going to happen," whether women's marriages would survive, Kiecolt-Glaser said.


The most important finding, she says however, is that this proves that "positive" interactions, along with their health implications, deserve as much study as "negative" interactions have garnered.


The National Institutes of Health supported the study.

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Thanks for sharing this Robin and Mertie...there are some things in this article that I don't really want to think too much about---I wonder if e-harmony or someone like that may incorporate some of these findings in their "compatibility" profile.


I remember reading a book a long time ago when I was a kid---it was called something like "stress without destress".

The whole premise of the book---is that STRESS is NATURAL---but it's the DIS-that we put into it that makes things hard for us.

Of course this was a "self-help" book from the late 60's or early 70's---and some folks think of those days as the "dark ages". Maybe they weren't so dark after all.


A couple of things to read if bored:




News and Commentary


Molecular Psychiatry (2003) 8, 253–254. doi:10.1038/sj.mp.4001323

Stress without distress: homeostatic role for KATP channels


L V Zingman1, D M Hodgson1, A E Alekseev1 and A Terzic1


1Departments of Medicine and Molecular Pharmacology and Experimental Therapeutics, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA


Correspondence: Dr A Terzic, Guggenheim 7, Mayo Clinic, Rochester, MN 55905, USA. E-mail: terzic.andre@mayo.edu


Stress is defined as a threat, real or implied, to the narrow range of physiological parameters necessary for survival, with the dynamic of existence comprising an ongoing sequence of stressful events and their consequences.1 Self-preservation is achieved through the general adaptation syndrome that is initiated by brain recognition of threat leading to modification of behavior and activation of the hypothalamic-pituitary–adrenal axis and autonomic nervous system.1 This ubiquitous response underlies the 'fight-or-flight' reaction by alteration of bodily functions to sustain a new performance level necessary for confrontation or evasion of threatening conditions.1 However, augmentation in performance is metabolically demanding, and requires a safety mechanism to prevent fatal exhaustion of resources. Recently, the ATP-sensitive potassium (KATP) channel, a cell membrane metabolic sensor, was identified as a critical component in maintaining the body's homeostasis during the adaptive reaction to stress, such that the reaction itself does not become deleterious to the organism.2


KATP channels, widely represented in metabolically active tissues, are formed through physical association of the pore-forming inwardly rectifying potassium channel, Kir6.x, with the regulatory sulfonylurea receptor, SUR.3 In this way, Kir6.2 and SUR2A generate cardiac and skeletal muscle KATP channels.4 Metabolic sensing occurs through modulation of Kir6.2 ATP-sensitivity by the SUR2A subunit ATPase activity such that stabilization of SUR2A in a posthydrolytic state favors K+ efflux through Kir6.2 leading to membrane hyperpolarization.5 These intrinsic channel properties, along with tight integration of KATP channel proteins with cellular metabolic pathways, are responsible for the rapid and precise metabolic modulation of membrane potential-dependent cellular functions.5 Vascular smooth muscle channels combine Kir6.1 and SUR2B,6 and channels in pancreatic beta-cells comprise Kir6.2 and SUR1.3 In neurons, various permutations of Kir6.1 or Kir6.2 and SUR1 or SUR2 coexpression form KATP channels.7 Such structural diversity defines a wide spectrum of KATP channel involvement in tissue-specific functions, yet the underlying property of the metabolic mediator remains consistent.


In the heart, while the role of KATP channels has been viewed as that of protection against the metabolic insult of ischemic injury, recent data support a broader interpretation of these channels as molecular mediators in the adaptive response to stress.2 Indeed, under exercise-stress, a natural trigger of the general adaptation syndrome,1 mice lacking KATP channels through genetic deletion of Kir6.2 perform at a significantly reduced level than age- and gender-matched normal controls.2 In stress situations, sympathetic stimulation augments cardiac output to support the body's immediate or anticipated requirement of enhanced performance. This augmented work imposes a significant demand on cardiac metabolic resources, mostly because of energy-consuming Ca2+ handling. To prevent cellular Ca2+ overload and associated energy depletion, increased Ca2+ influx is normally balanced by a compensatory increase in outward potassium ion currents. This protective feedback mechanism is absent in myocardium lacking KATP channels.2 Hearts from Kir6.2-knockout mice display less shortening of the action potential after adrenoreceptor stimulation than normal hearts. In fact, Kir6.2-knockout mice demonstrate a phenotype of increased vulnerability under stress manifested by aberrant regulation of cardiac membrane excitability, inadequate calcium handling, and fatal ventricular arrhythmia.2 This underscores the vital role of KATP channels in the coordination of cardiac function with changing metabolic conditions.


Moreover, KATP channels regulate vascular tone, and thereby the delivery of metabolic resources to match demand.8 Furthermore, these channels are central in setting blood glucose levels by regulating insulin exocytosis in pancreatic beta-cells and insulin-dependent glucose uptake in skeletal muscle.3,9,10,11,12 Thus, KATP channels adjust the function of end-organ systems critical in the adaptive response to stress.


Ultimately in the hierarchy of the general adaptation syndrome, KATP channels in the nervous system operate via changes in neuronal excitability as a feedback mechanism coupling the adaptive response to the metabolic state.7,13,14 In particular, KATP channel activity defines the firing rate of glucose-responsive neurons identified in a number of discrete brain areas including the ventromedial, arcuate and paraventricular nuclei of the hypothalamus, substantia nigra, as well as in the area postrema and the tractus solitarius nucleus.7,13,14,15 When extracellular glucose increases, glucose metabolism in neurons promotes KATP channel inhibition leading to membrane depolarization and increased neuronal activity. Conversely, with the decrease in extracellular glucose levels, ensuing changes in cellular metabolism favor KATP channel opening associated with a reduced rate of neuronal firing. KATP channels are gated not only in response to oscillations in extracellular glucose, but also respond to the direct action of stress-sensitive neuromediators, including endorphins, adenosine and leptin.15 Changes in neuronal activity translate into modification of the adaptive response through behavioral effects, and activation patterns of the hypothalamic-pituitary–adrenal axis. Kir6.2-knockout mice exhibit a severe defect in hypothalamic-pituitary–adrenal axis-dependent glucagon secretion and food intake in response to neuroglycopenia and hypoglycemia.14 Further, KATP channels have been implicated in the control of satiety and pain perception.7,15


Thus, the KATP channel/enzyme protein complex, integrated with cellular and systemic metabolism, acts at various levels to ensure energetic homeostasis under the augmented functional demands of the adaptation reaction (Figure 1). In this way, the KATP channel serves as a unifying molecular coordinator of metabolic well-being under stress. This homeostatic function identifies the role of KATP channels in the hierarchy of molecular events underlying propagation of the general adaptation syndrome.



KATP channels maintain balance between the adaptive response to stress and metabolic resources to ensure survival. KATP channels, comprised of the pore-forming Kir6.x and regulatory SUR subunits, are represented in metabolically active tissues where they support execution of the general adaptation syndrome under stress and allocation of resources to balance the need for escape or confrontation with prevention of metabolic exhaustion. In this way the KATP channel, with a broad range of tissue-specific properties, acts as a unifying molecular coordinator of the body's response to stress.


Is this why my sodium levels rise and fall?





14 October 2002

How the heart copes with stress without distress


Mayo Clinic researchers today identified a genetic basis for the heart's ability to withstand fight-or-flight responses: a protein called Kir6.2 enables the heart to react to stress without distress.


Mice lacking this key protein had reduced cardiac tolerance for both exercise- and adrenaline-like stress. Nearly three-quarters (73 percent) of the Kir6.2-deficient mice died within 14 minutes after a stressor challenged their cardiac response -- yet all the mice that possessed Kir6.2 survived the stress tests.


As reported in the 1 October edition of Proceedings of the National Academy of Sciences (PNAS), the research provides provocative leads to understanding and treating stress-related disorders of the heart. These may range from sudden death of highly conditioned athletes to the cumulative effects of psychological stress at work, school or in family life.


"We have identified in the heart a protective mechanism against stress that is roughly analogous to an automatic sprinkler system that douses a fire in an emergency," says Andre Terzic, M.D., Ph.D, lead researcher. "The Kir6.2 protein senses stress and prevents damage to the heart by helping the cells maintain equilibrium even under peak workloads. Lack of Kir6.2 protein function causes sudden, irreversible damage to heart cells, which could lead to heart failure."


In the study, the Mayo Clinic team led by Dr. Terzic compared mice in which the gene that produces the Kir6.2 protein had been eliminated to a control group of mice that possessed the Kir6.2 protein. Their goal was to determine whether Kir6.2 enables heart cells to maintain high levels of activity without suffering damage, and to discover how it works.


Study Findings

In treadmill testing, the normal mice tolerated more than three times the workload that the Kir6.2-deficient mice could. Both groups of mice were also tested under stress induced by a compound similar in effect to adrenaline, the body's natural fight-or-flight hormone. In mice lacking Kir6.2, hearts did not contract as completely under stress – and 73 percent developed severe heart rhythm disturbances called arrhythmias, then died suddenly.


By contrast, none of the normal mice experienced a fatal arrhythmia.


Study Significance

Kir6.2, a protein common to all animals, is at the core of the KATP channel complex that choreographs an intricate chemical dance between potassium and calcium flow in the heart. By conducting potassium, the KATP channel enables the cells to more quickly restore electrical balance following each heartbeat, thus limiting the entrance of calcium into the cells.


"The system needs to be fully orchestrated," says Dr. Terzic. "It must have perfect harmonization to bring sufficient calcium for contraction without overdoing it." When the orchestra is "off tempo," the chemical dancers are out of step. The result: cardiac distress under stress.


The Mayo Clinic study found that heart cells in the mice lacking Kir6.2 overloaded with calcium – and this damaged cell structure. Administering calcium-channel blockers, a common heart medication, to those Kir6.2-deficient mice prevented the fatal arrhythmias in five out of six.


Thus, the Mayo Clinic study shows that Kir6.2 is crucial to survival under the sudden rush of cardiac output required by the flight-or-fight response of the sympathetic nervous system to threats – be they from a saber tooth cat or a bear market. "Because of the selective advantage it confers, Kir6.2 has been maintained through evolution in the gene package of many organisms," explains Dr. Terzic.


The next steps for the Mayo Clinic researchers will be developing the diagnostic and therapeutic potential of these findings. A blood test could identify individuals who are deficient in KATP channel proteins, or whose supporting protein-signaling system isn't working, and drug or gene therapies could compensate for those deficiencies. "Understanding that this protein is so important, we can now work on ways to repair it when defective within the cells, or to boost its ability to respond," Dr. Terzic concludes.


Original source: Mayo Clinic



30 September 2002

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