Stress

What is Stress and how does it Affect You?

Physiological or biological stress is an organism's response to a stressor such as an environmental condition. Stress is the body's natural method of reacting to a challenge. Stimuli that alter an organism's environment are responded to by multiple systems in the body. Through triggering these adaptive responses, stress can alter memory functions, reward, immune function, metabolism and susceptibility to diseases. Too much stress can lead to exhaustion.

Activation of the autonomic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis are primary drivers of the stress response. The autonomic nervous system influences heart rate, digestion, respiration, and other systems, to instantly ready the body to respond to a threat. Evolutionarily, this rapid response has been crucial for survival in dangerous situations. The HPA axis is the body's hormonal response to stress. Hormones act more slowly than nerve conduction and affect biology in a more chronic manner. For this reason, persistent stress is clinically measured through this axis. In particular, measures of the stress hormone cortisol (secreted by the adrenal glands, the "A" in HPA) in blood, saliva, and hair, are used to measure acute and chronic stress. Prolonged increases in stress hormones are thought to underlie many of its long-term negative effects.1

HPA-Axis

The perception of stress releases corticotropin releasing hormone (CRH) in the brain. This signals the pituitary gland, also in the brain, to release adrenocorticotropin hormone (ACTH), which enters the blood stream and diffuses throughout the body. The adrenal glands, which sit atop each kidney, release cortisol in response to circulating ACTH.

Negative Effects of Stress

Today, however, prolonged activation of this sytem, primarily through psychological pressure, is a primary driver of a variety of medical problems. HPA axis dysregulation has been measured in a wide variety of disorders - demonstrating what a pervasive role stress biology plays in medical disorders. Type II diabetes and poor glycemic control result in overactivity of the HPA axis.2Stress pathways are upregulated in Alzheimer's disease.3The HPA axis is dysregulated in major depressive disorder.4Chronic stress is also linked to the development of hypertension, cardiovascular disease, stroke. It is also well known that increased HPA axis activity is a strong risk factor for cardiovascular disease and stroke.5

Positive Effects of Stress

Viewing stress as ONLY negative is also inappropriate, as short-term activation of the stress system can have a variety positive effects. Short-term stress can improve recovery after surgery, increase the efficacy of immunity after vaccination, and improve the response to therapy in cancer patients. An interesting 2011 study found that individuals who believe that stress affects their health and reported high levels of stress, had increased mortality. Individuals who reported high levels of stress, but did not believe it to significantly affect their health did not die at rates higher than low-stress individuals. Though this was an observational study and as such cannot claim a cause-effect relationship, this investigation suggests that perception of stress may be more important to health outcomes than the stress itself - further emphasizing the role that psychological stress and our conception of it plays in our lives.6

Stress and performance

The dogma for a long time was that to achieve maximal performance, an intermediate level of stress is required - as represented by te Yerkes-Dodson curve.

yerkes-dodson Yerkes-Dodson Curve

However, it is now known that performance, and its relationship with stress, depends on each individual and what task is being performed. Most simply, high energy tasks such as athletic performance, require higher levels of stress signaling to achieve peak performance. On the other hand, tasks requiring sustained attention and fine manipulations generally require lower degrees of stress activation for maximal performance.

How can the effects of Stress be modulated?

The link between stress and disease is high. While in many cases, it is equivocal whether the disease is resulting in increased stress, or whether the stress is resulting in disease, the psychological effects of stress and its relationship with mental and physical performance are clear. While work is needed to understand individual responses to stressful situations, it is likely that stress reduction can be a positive step for many people - both from the perspective of reducing psychological burden, and to optimize performance. In particular, many individuals engage in occupations where quiet, stationary productivity are much more valued than athletic activity; so reducing stress levels to optimize concentration in these situations can be a huge enhancement to daily life for many people. There are a variety of strategies to tackle stress reduction, from nootropics, to behavioral modifications.

Nootropics

Many psychiatric medications are very effective at combat stress (antipsychotics, antidepressants), but have extreme side effects, such as weight gain and potentially increased cardiovascular and metabolic risk. Natural compounds/nootropics with anti-stress effects may be an effective method by which we can tamp down the mental and physical effects of these everyday stressors.

L-theanine has been shown to reduce a variety of measures of stress7

l-theanine and stress Measures of stress were taken during a stressful arithmetic task in four groups: control, placebo, and two L-theanine groups. A. The subjective feeling of stress was reduced by L-theanine during the task (as compared to placebo). B. Salivary α-amylase (a biomarker for stress) was reduced in the theanine groups as compared to placebo. C. Heart rate variability (increased heart rate variability is a marker of stress) was reduced in comparison to placebo.

Rhodiola rosea has been shown to reduce measures of stress. In one study, fatigue in students during an examination period, in particular, physical fitness, mental fatigue, and self-reported well-being were improved by rhodiola.8In a 2008 double-blind, placebo-controlled trial, it was shown that morning salivary cortisol (an HPA axis measure of stress), is reduced after 28 days of rhodiola consumption, in patients with diagnosed fatigue syndrome.

salivary cortisol rhodiola The placebo group is shown on the left, with no significant difference in salivary cortisol on day 1 (pre-treatment) and day 28 (after 28 days of placebo consumption). On the right, 28 days of rhodiola reduce salivary cortisol in these patients

Ashwagandha, or Withania somnifera has also been shown to reduce stress. In a 2012 study, that investigated a variety of different measures of stress and anxiety, it was shown that 60 days of 300 mg of high-concentration, full spectrum ashwagandha, improved all measures of stress that were taken.9

  1. McEwen, B. S. (2007). Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev, 87(3), 873-904. doi:10.1152/physrev.00041.2006

  2. Incollingo Rodriguez, A. C., Epel, E. S., White, M. L., Standen, E. C., Seckl, J. R., & Tomiyama, A. J. (2015). Hypothalamic-pituitary-adrenal axis dysregulation and cortisol activity in obesity: A systematic review. Psychoneuroendocrinology, 62, 301-318. doi:10.1016/j.psyneuen.2015.08.014

  3. Pomara, N., Greenberg, W. M., Branford, M. D., & Doraiswamy, P. M. (2003). Therapeutic implications of HPA axis abnormalities in Alzheimer's disease: review and update. Psychopharmacol Bull, 37(2), 120-134.

  4. Pariante, C. M., & Lightman, S. L. (2008). The HPA axis in major depression: classical theories and new developments. Trends Neurosci, 31(9), 464-468. doi:10.1016/j.tins.2008.06.006

  5. Rosmond, R., & Bjorntorp, P. (2000). The hypothalamic-pituitary-adrenal axis activity as a predictor of cardiovascular disease, type 2 diabetes and stroke. J Intern Med, 247(2), 188-197.

  6. Keller, A., Litzelman, K., Wisk, L. E., Maddox, T., Cheng, E. R., Creswell, P. D., & Witt, W. P. (2012). Does the Perception that Stress Affects Health Matter? The Association with Health and Mortality. Health Psychol, 31(5), 677-684. doi:10.1037/a0026743

  7. Kimura, K., Ozeki, M., Juneja, L. R., & Ohira, H. (2007). L-Theanine reduces psychological and physiological stress responses. Biol Psychol, 74(1), 39-45. doi:10.1016/j.biopsycho.2006.06.006

  8. Spasov, A. A., Wikman, G. K., Mandrikov, V. B., Mironova, I. A., & Neumoin, V. V. (2000). A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine, 7(2), 85-89. doi:10.1016/s0944-7113(00)80078-1

  9. Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med, 34(3), 255-262. doi:10.4103/0253-7176.106022

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