Learning What Stress Does to the Mind is Key to Understanding What it Does to the Body

Modern life is full of stress, and understanding how stress affects the brain is essential to developing ways to prevent its harmful effects on the body, according to Gregory Fricchione, MD, of Harvard Medical School.

Modern life is full of stress, and understanding how stress affects the brain is essential to developing ways to prevent its harmful effects on the body, according to Gregory Fricchione, MD, of Harvard Medical School.

Dr Fricchione’s Sunday talk, “Mind/Body Medicine: The Link Between Clinical Medicine and Public Health,” gave attendees at the 167th Annual Meeting of the American Psychiatric Association a lesson in the brain’s evolution alongside insights on how stress plays out in the population as obesity, type 2 diabetes mellitus (T2DM), depression, and cardiovascular disease.

The development of vaccines, antibiotics, and other drugs have allowed the world’s doctors to tame many communicable diseases over the past century. It’s the noncommunicable diseases that are causing increased suffering and cost to the US healthcare system and, more broadly, to the world economy, Dr Fricchione said. He quoted data from a report that the Harvard School of Public Health prepared for the World Economic Forum, which stated that neuropsychiatric disorders, cardiovascular disease, chronic respiratory disease, cancer, and diabetes will cost $47 trillion by 2030.1

“For psychiatry, the story gets even more intense,” Dr Fricchione said. The common thread among these diseases is the brain and body response to stress, so the key to stemming rising costs and economic loss is to learn, “What we can do as psychiatrists to help out patients mount the best defense against noncommunicable disease, and especially stress.”

Bending the curve, he said, “cannot only mean interventions once you have an illness. You have to push it upstream to ask what you can do for health promotion and disease prevention.”

Dr Fricchione said that understanding the pressure the human body and mind face starts with understanding the concepts of attachment theory, allostasis, and resiliency. The sense of security that comes as humans attach to each other is especially important for children, and if it is threatened or severed, that sense of “loss” shows up later, in the form of heart disease, cancer, chronic lung ailments, skeletal fractures, sexually transmitted diseases, and liver failure.

Allostasis refers to the body’s natural tendency to work toward stability; when confronted with stress, the body has to work much harder to handle the “allostatic load.” Afflictions like heart disease and diabetes also befall those who bear too great of a burden.

“This has to be a core ingredient in how we plan medicine, and in how we plan public health (responses),” Dr Fricchione said. With rising rates of diabetes and obesity, especially among children, he said, “Shouldn’t we be having a Manhattan Project in this country to deal with this problem?”

By contrast, when the body is unbalanced and feels a sense of “insecure attachment,” that leads to the body developing defenses, including the “use of external regulators to alter mood,” and “maladaptive protective factors.”

Dr Fricchione then walked the audience through a short course in evolutionary physiology, showing how the brain developed over millions of years, continually pushing the hypothalamus, the regulator that links the nervous system to the endocrine system, from the front of the brain to its underside. The anterior cingulate, which he described as the “Grand Central Station” of the brain, evolved toward the front to process all the incoming signals and, along with memory, make the best decisions about whether to approach or separate, or to attach. Thus, Dr Fricchione said, humans went from having a very primitive sense of reacting to the world to an increasingly sophisticated sense of reacting to danger or stress.

“Stress becomes a challenge, a stimulus,” he said. “What stress means, based on evolution, is that something in your experience, combined with something external, is giving you a signal that you, as a mammal, are being threatened with separation.” Sources of stress can be social conflicts, job losses, or serious illnesses; and all require constant adaptations. Too much stress leads to a state of hyperarousal.

Studies have revealed the connection between chronic social isolation and activation of nuclear factor kappa B (NF- kB), which has a key role in inflammation and immune response.2 NF-kB is overactive in a number of inflammatory diseases, including rheumatoid arthritis. Understanding this link, Dr Fricchione said, will lead to changes in psychiatric care.

“When we treat patients for depression, we might have the ability to dampen the stress response,” he said. Having parts of the brain associated with stress response “firing all the time” isn’t good for the brain or the body. Psychiatry will have to aim to get these parts of the brain to “chill out,” Dr Fricchione said.

“When stress exceeds resiliency, we see burnout. We see compassion fatigue. Stress can become overwhelming and persistent, and this leads to a downgrading of function,” he said. “When stress cannot be metabolized by the allostatic brain mechanism, both health and performance suffer.” Thus, the connection between stress and heart function, and stress and visceral pain. Fibromyalgia should be measured differently, he said, and it should be understood that “an overwhelming achiness” is both stress-related and also an inflammatory response.

Stress hits at the cellular level by affecting the mitochondria and their role in energy regulation. “There’s a relationship between inflammatory response syndrome and mitochondrial stress; your cells are working day and night producing that inflammatory response,” Dr Fricchione said. “It doesn’t do you any good to stay on high alert.”

Mitochondrial stress can be mitigated with medication to increase resilience, which essentially tones down the natural fear response.

What does all this mean for public health? Payers like Kaiser are recognizing the role that stress plays in disease. For example, there is increased awareness of the need to address stress among caregivers for the ill. Efforts to repair the attachment response will simply make people feel better, Dr Fricchione said.


  1. Bloom DE, Cafiero ET, Jané-Llopis, E., et al. The global economic burden of noncommunicable diseases. Geneva: World Economic Forum; 2011. Harvard School of Public Health. http://www3.weforum.org/docs/WEF_Harvard_HE_GlobalEconomicBurdenNonCommunicableDiseases_2011.pdf. Accessed May 7, 2014.
  2. Djordjevic J, Djordjevic A, Adzic M, Niciforovic A, Radojcic MB. Chronic stress differentially affects antioxidant enzymes and modifies the acute stress response in liver of Wistar rats. Physiol Res. 2010;59(5):729-736.
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