Connecting the dots: stress and inflammation

Chronic inflammation is associated with auto-immune disorders such as asthma, irritable bowel syndrome (IBS), metabolic disorders, and allergies with which many people struggle, thereby finding their vitality reduced. People sometimes respond to these disorders by engaging in proper self-care, daily exercise, and well-balance diets. People also respond by engaging in self-defeating behaviors. People try to self-medicate with alcohol. They try to regulate and regain their emotional equilibrium in the face of social stressors by acting out in way that sabotage their own long-term well-being.

Lack of exercise and poor nutritional choices along with excessive use of alcohol, street drugs, gambling, sexual misadventures, binging, and chronic subclinical sadness belong on the list of self-defeating behavioral reactions. 

The bottom line? When people practice healthy responses, not self-defeating ones, the body mobilizes and applies its infection fighting responses to social stressors, even though the latter are not infections. This makes considerable sense if one considers that an adaptive response to overwhelming social stress is to withdraw from the conflict and retreat to “sickness behavior.” The stressed-out individual retreats and avoids the stressful situation. The body makes one do this as a survival mechanism, getting out of a situation perceived to be “no win,” even if one’s stubbornness of spirit would make one willing to fight on. Never was it truer, the spirit is willing, but the flesh is weak.

The socially defeated person nurses his emotional wounds, as noted, by going to bed, with reduced appetite, lower energy, less enjoyment, less attention, and a need for sleep. The person finds his emotional and physical resource depleted. He takes to his “nest” to recover; and here is the punch line: The person acts depressed. 

Additional evidence of the link between inflammation and symptoms of depression comes from modern cancer treatments.^[i] Cancer treatments target tumors and cancerous processes by means of interventions that simulate immune systems reactions. These reactions use the above-cited cytokines called “interleukon” and “interferon.” One result of the cancer treatments that surprised cancer doctors is that patients receiving such interventioilns succumbed to depression. They satisfied clinical criteria for major depression disorder (MDD). 

Note that the person receiving the treatment was not depressed beforehand. The person was not depressed because they have cancer, which can indeed be a “depressing” thing. No, the depression occurs even in people who have a positive attitude and are energetically fighting the disease, who otherwise feel okay emotionally. The symptoms of depression are evidentially a side effect of the treatment (albeit one which is not as toxic as the cancer itself). As a further confirmation of this, the side-effect yields to pharmacological treatments of depression such as antidepressants, and the person regains their standard non-depressed outlook once the cancer treatment is finished. 

Psychologists Suzanne Segerstrom and Gregory Miller demonstrate that the immune system is not as autonomous as it was once thought to be.^[ii] The immune system provides a pathway for the environment to influence the regulation of genes. Note that to be fully buzzword compliant “epigenesis” is the process by which the environment influences the regulation of the biologically given set of genes with which the person is endowed at birth. 

Popular biological wisdom is that a person’s genes are like a set of cards in a “no draw” game of poker that one is dealt at the beginning. You play the hand you are dealt without being able to exchange any cards. Even if you don’t like a card you are dealt, you cannot change it. On the contrary, the approach of epigenesis says, “Yes, you still have to play the hand you are dealt, but you get to exchange a couple of cards,” based on interacting with the environment. 

The physical and social environments do not just cause occasional, rare random mutations on genes; the environments are critical in activating or deactivating existing genes to produce diverse expressions of our biological capabilities, our biological selves. In short, the interaction is two-way, both from the genes to the organism and from the organism and its environment to the genes (or more properly speaking, the “genome,” the set of genes that includes all the genetic material governing the organism’s survival). Now add the stresses of the social environment to the physical mix of stressors. 

According to Segerstrom and Miller, the immune system responds to signals from the body’s nervous system and the endocrine system. The immune system is modifiable and responds to the signals of cytokines and macrophages as they produce antibodies to fight bacterial diseases. This is where things get interesting. 

Environmental stressors, to which the nervous system and endocrine system respond, elicit responses from the immune system by way of activation of genetic mechanisms that, in turn, perform protein synthesis, a major path by which the organism responds and attempts to maintain its equilibrium and well-being. 

Strictly speaking, stress affects the immune system in at least two ways. Stress does not always reduce immunity. It tends to reduce—“down regulate” is the term of art—the anti-viral response (viruses being a different form of attack than bacteria); and it tends to “up regulate” the response to wounds and bacterial infection. Due to the production of inflammatory substances designed to combat a bacterial infection (which bacteria does not exist in the scenario of chronic social stress), the individual becomes vulnerable to life style and autoimmune disorders. 

Subclinical physical problems tend to get emotionally and psychically elaborated in notoriously difficult to manage inflammations that manifest themselves as head aches, irritable bowel, asthma, allergies, lower back pain, and so on. 

The best defense is often a good offense. Apparently the immune system agrees. Whether due to the haphazard design of the immune system or a defect in encoding the symbolic threat, the immune system counter-attacks against stress as if it were an all out attack by an infectious agent or wound. 

In the case of chronic stress, the side effects of the counter-attack are inflammation. When the stress is chronic, the inflammation becomes chronic, too. This is the situation of many contemporary, stressed out individuals, struggling to survive modern life. The resulting “gotcha” is that many chronic stressors are largely symbolic. The stressed out person is not threatened by physical danger. The outcome is commonly observed: people who are chronically “stressed out” tend to get more colds and flu due to the down regulation of the anti-viral response. 

The cytokine theory of depression shows us some of the diverse ways by which people express their stress and suffering. The cytokine theory of depression indicates that people express their chronic stress by displaying “sickness behavior.” 

How does it work, and what to do about it?

Under standards conditions of moderate stress, the body regulates its own inflammatory activity. The neuroendocrine system regulates the body’s response to stressors. Substances called steroids—“glucocorticoids”—are released to balance and limit the inflammatory action. However, in chronic stress the process of regulation goes astray.

The hypothalamic-pituitary-adrenal (HPA) axis is a major part of the neuroendocrine system. This set of functions is a part of the lower brain stem. It regulates the body’s reaction to external stressors by providing energy and focusing attention. (Granted, the adrenal glands are not located in the brain, but interact with it.) The HPA axis gets activated to release these and related steriods. 

However, under chronic stress, the glucocorticoid receptors seem to get fatigued. In effect, the receptors get “stressed out.” They become less responsive when they are under chronic stress, constantly being over-stimulated, in a process that is not well understood. This phenomenon is called “glucocorticoid insensitivity.”

For example and as near as we can tell, Slavich and Cole report that steriod—“glucocorticoid”—receptors typically act to “turn down” the production of inflammation-related substances. However, during chronic psychosocial stress or actual threat, glucocorticoid receptors fail to “down regulate” the glucocorticoid responsive genes the way they are supposed to do so. This is in spite of the glucocorticoid levels being either normal or elevated.^[iii] They stop working or are no longer effective in countering inflammation. 

Further confirming this troubling outcome, a correlation was found between immune function and cortisol levels in depressed patients.^[iv]The result is the sickness behavior that we have been describing as the body’s inflammatory response is prolonged. 

Notice that these steriods then become an indicator—a “bio marker” to use the technical term—of stress. In fact, the steriods are anti-inflammatory and anti-stress; but the body has stopped responding to them; and so they continue to “float around” in the organism, getting correlated with stress without functioning effectively as the anti-inflammatory substance that they are supposed to be. This is something that the popular treatment of cortico-steriods has sometimes gotten mixed up. 

For example, in an otherwise penetrating and incisive treatment of stress, Arthur Ciaramicoli describes cortisol as a stress hormone. Cortisol is a villain in this narrative, and stress reducing or promoting activities are narratively associated with its departure or arrival. “Correlation is not causation” strikes again. Nevertheless, his conclusions about the value of dialing up empathy and dialing down negative self-talk through understanding and empathic responsiveness remains valid. The initiative to “wrapper” the skills training and tips and techniques of CBT in an empathic cacoon is a worthy one. ^[v]

In “stressed out” people, steriods as a group (including cortisol) are anti-inflammatory hormones that are not working as designed. The idea is that body was never designed to deal with chronic social stress as it occurs in modern, technological society, and further innovations or simplifications are needed to overcome the challenge of responding to the stress. 

The meta-analysis of some 30 years of research by Segerstrom and Miller reports a significant association of depression (and chronic inflammation) with coronary heart disease, rheumatoid arthritis, stroke and other diseases where macrophage activation occurs. The authors account for the 3:1 female/male incidence of depression ratio by estrogen’s ability to activate macrophages; and the relatively low rate of depression in Japan as consistent with the suppressive effect of fatty acids and fish oil on macrophages.^[vi]

According to Segerstrom and Miller’s interpretation, “depression” is a redescription of “inflammation.” If you are depressed, you need anti-inflammatory intervention. 

A major depressive disorder involves real suffering, and in no way does one want to make light of such suffering. Nevertheless, the “out of the box” redescription cited-above suggests that you are not really depressed, you just have an inflammation. Aspirin is an anti-inflammatory. Therefore: “Take two aspirin and call in the morning.” Pause for a laugh. This unsubtle joke, which you must admit is suitable for polite company, made many of my MD colleagues laugh out loud; and it points to the reason why this approach to depression has not received more attention, though it has been validated and available since at least the mid-1990s:^[vii]

•  It would mean having to develop an entire class of anti-inflammatory antidepressants, which, in turn, would potentially undercut the vast existing market of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) (of which the “poster child” is Prozac).
• It is by no means clear that such development of a new class of drugs would be feasible or (more to the point) profitable.
• Alternative interventions already exist that reduce stress and inflammation—and empathy is towards the top of the list of those. 

We take a step back and note that, with the publication of Peter Kramer’s Listening to Prozac (1991), pharmacological interventions for depression knocked the legs out from under all forms of talk therapy. 

Even if SSRIs (such as Prozac (the brand name for fluoxetine)) have not lived up to their initial, exaggerated promise, the economics of current medical system prescribing prefers fifteen-minute medication management sessions over forty five minute conversations for insight and possibility. 

The reimbursement system is adhering to this assessment even in the face of the hard-to-quantify trade-offs between quality and quantity. 

The conversation about evidence-based treatment is stuck in a loop of an either/or preference for medication over conversation. Evidence is available for the efficacy of each in sometime diverging, sometimes overlapping contexts. The economics of talk therapy, even CBT, are under-privileged and marginalized by many insurance payers and their practitioners. 

This raises the engaging question of how SSRIs intersect with those depressed individuals, whose biomarkers show increased pro-inflammatory immune response and related increases in glucocorticoid resistance, matching the previously described effects of major depressive disorder. 

As this book goes to press [Q1 2018], results are inconclusive. High blood serum levels of serotonin are completely consistent with high biomarkers for inflammation and vice versa. One likely possibility, though speculative, is that “major depression” is not a natural category; and one can obtain the symptoms of major depression defined in the Diagnostic and Statistical Manual (any version) by multiple molecular pathways. 

Once again, it is speculation, but just as scientific advances are showing that cancer is not a single disease at the molecular level, so too depression may well turn out to be multi-dimensional and not a single disorder. Nevertheless, this brings us back to the question; People are stressed out—suffering—what do we do about it? 

Connecting the dots: anti-inflammation and empathy

This just in. The patients of medical doctors who score well on tests for empathy have superior control over their “bad” cholesterol in comparison with those who score less well. (In fact, this is not “just in,” but was published in 2011 as indicated in the next end note.)

M. Hojat and his colleagues found that patients of physicians with high empathy scores were significantly more likely to have good control of hemoglobin A1c (56%)—a bio-marker for diabetes—than were patients of physicians with low empathy scores (40%, P .001). 

In addition, Hojat reported that the proportion of patients with good control over low density lipid cholesterol (LDL-C)—the so-called “bad” cholesterol—was significantly higher for physicians with high empathy scores (59%) than physicians with low scores (44%, P < .001).^[viii]Hojat also reported that the physician’s empathy had a unique contribution to the prediction of optimal clinical outcomes even after controlling for the physician’s and patient’s gender and age, and the patient’s health insurance. 

Thus, anti-inflammatory interventions exist that have been shown to make a difference in controlled experiments, evidence-based research, and peer-reviewed publications. Empathy is at the top of the list. 

This bear repeating: empathy is at the top of the list, but is not the only thing on it. Spiritual practices such as Yoga, Tai Chi, mindfulness (meditation), also are on the list. These are not reducible to empathy (or vice versa), but they share a common factor: an outcome of reduced inflammation. 

Stress reduction practices such as receiving empathy from one’s doctor put the person in touch with her or his immediate experience. They promote the person experiencing life without anything added, without filters, without labels and categories. And in specific cases (cited below), they can be shown in evidence-based studies to reduce the bio markers of stress and stress-related life style disorders such as high cholesterol, diabetes type 2, and so on. People tend to feel better, perform better, enjoy expanded vitality in conjunction with these practices. Therefore, we shall cast a wide net in gathering reminders as to how to reduce stress in such a way that the stress reduction practices gets inside the body and make a difference. 

The empathy lesson? Peer-reviewed research studies have provided an evidence-based link between practitioners who deliver empathy to their patients and favorable healthcare outcomes. What is interesting is that these evidence-based studies exclude psychiatric disorders and emphasize outcomes for life style disorders such as reduced cholesterol and type 2 diabetes in order better to isolate and control the empathic input to the process, which is otherwise so pervasive in a psychiatric context. 

A separate study by Del Canale and colleagues showed that physicians with high empathy scores had patients with significantly fewer metabolic complications from diabetes.^[ix]

The study concluded that these results indicate physician empathy is significantly associated with clinical outcome for patients with diabetes mellitus and should be considered an important component of clinical competence. It gets better—for empathy. These are not just “one off” studies. A meta-study of healthcare outcomes across all kinds of doctor visits, in which objective measures such as blood pressure were available, indicated a significant correlation between empathy and favorable outcomes. 

In the meta-study, John Kelly and his colleagues, including Helen Riess, report on empathy publications of randomized control trials (RCTs) in adult patients. In these RCTs, the patient-clinician relationship was systematically manipulated and healthcare outcomes were either objective (e.g., blood pressure) or validated subjective measures (e.g., pain scores). A broad and diverse variety of disorders were engaged empathically. Disorders studied included patients with diabetes, osteoarthritis, fibromyalgia, lower respiratory infection, oncology, osteoarthritis, hypertension, smoking, somatic complaints, and asthma. The median patient sample size was 279 (range: 85 to 7,557). 

The researchers acknowledge that they cannot be sure if, in the context of empathic medical practice, the favorable outcome is due to improved compliance with physician guidance, patient motivation to take action to recover well-being, education, the self-healing properties of the body under reduced stress (my favorite interpretation), or (mostly likely) a combination of factors. On the one hand, further research is needed; on the other, results are results. Once again, correlation points to a significant path to improved outcome through empathic treatment, but is not causation. 

With that caution in mind, empathy has been shown to correlate with reduced duration of the common cold. Now no one is saying that empathy is the cure for the common cold; but the results are definitely suggestive of the healing powers of stress reduction: “In those physicians with perfect CARE scores (Consultation and Relational Empathy), cold durations were shorter (mean 7.10 days versus 8.01 days) [….] In these models, a perfect score also correlates with a larger increase in IL-8 [(interleukin 8) a cytokine] levels.”^[x] That is, the immune response was increased.

The researchers further engaged and evaluated immune response by measuring concentration of interleukin 8 (IL-8) from nasal wash specimens at enrollment and at a follow-up visit some 48 hours later. IL-8 is an inflammatory cytokine found in nasal secretions. It increases with viral upper respiratory infection. It is reportedly one of the best, single markers of immune response for upper respiratory infections acquired in a community setting; it correlates well with symptoms; and is reliably measured.  If we look carefully, we can see the hype in the media and press coming into view

The researchers concluded that empathy, as perceived by patients having a common cold, significantly predicts subsequent duration and severity of illness and is associated with immune system changes. My conclusion? Do not under-estimate the healing powers of empathy! 

However, empathy is not the only intervention that correlates with improved results. Other practices such as meditation (mindfulness), sitting, yogic meditation, and Tai Chi produce a similar result. Several paths are available to stress reduction. We look at these alternative paths. 

For example, W. W. Thaddeus Pace and his colleagues at Emory University report that meditation practices impact physiological pathways, including the immune and neuroendocrine systems, which are regulated by stress and are relevant to diverse diseases.^[xi] How could they possibly know? The researchers divided people into meditators and non-meditators for testing. The researchers took blood (plasma) samples, and reported the results. 

In plain English, the bio-markers of stress went down significantly for those engaging in meditating compassionately, thinking kind thoughts and thinking charitable thoughts. The researchers report that physiologic and behavioral responses to the tier social stress test (TSST) were determined by repeated assessments of plasma concentrations of interleukin (IL-6) and cortisol as well as total distress scores on the Profile of Mood States (POMS). For the meditating group, increased meditation practice was correlated with decreased IL-6 and improved distress scores. More evidence proving common sense? Individuals who meditated more enjoyed proportionally reduced stress. 

The researchers cautiously conclude that engagement in compassion meditation (thinking kind thoughts, being charitable in one’s thoughts) may reduce stress-induced immune and behavioral responses. Once again, empathy and compassion are distinct; but both get one in touch with one’s own experience in such a way that one is accepting of whatever it is that one is experiencing, thereby reducing conflict and enabling the spontaneous stress reduction process to get traction. 

Family members and care-takers that provide support and care for people with Alzheimer’s or other forms of dementia are vulnerable to a variety of stress-related disorders. Providing such care is extremely stressful for many reasons, including the inability of the patient to acknowledge the contribution of the care-taker and the destructive nature of the disease (i.e., the frequent absence of an empathic response). David Black and his colleagues Steve Cole and Michael Irwin (and others) at the University of California, Los Angeles, reported that dementia caregivers who practice meditation show improvement in their own mental health indices such as depression and anxiety, which are indices associated with inflammatory markers such as IL-6. ^[xii]

Black and Cole investigated if yogic meditation changes the activity of inflammatory and antiviral pathways that shape gene-mediated immune system response. Forty-five family dementia caregivers were randomized either to Kirtan Kriya Meditation (KKM) or Relaxing Music (RM) listening for 12 minutes daily for 8 weeks and 39 caregivers completed the study. Genome-wide transcriptional profiles were collected from peripheral blood leukocytes sampled at baseline and 8-week follow-up. 

Without going into the wealth of details provided here, the researchers identified a reversal of patterns previously linked to stress. Their study concluded that a brief daily yogic meditation intervention reverses the pattern of increased pro-inflammatory cytokines and decreases antiviral response genes previously observed in healthy individuals confronting a significant life stressor. 

Eight weeks of structured yogic meditation reversed patterns of increased pro-inflammatory genes and decreased genes previously associated in healthy individuals with reduced inflammation. Meditating reduces stress and enhances immunity.

The authors generalized that adverse life events such as “social isolation, imminent bereavement, PTSD, chronic loneliness, social stress, and low socioeconomic status” increased inflammation-related gene activation and decreased the activity of innate antiviral genes. Once again, meditating reduces stress and enhances immunity.

Michael Irwin and Richard Olmstead reported on the stress reducing properties of Tai Chi Chin ((TCC) a “soft” Chinese martial art that practices continuous, slow motion flowing movements). The researchers describe TCC as a behavioral intervention. Practicing it daily reduces circulating levels of inflammatory bio-markers (interleukon-6 (IL-6)) in older adults (the target population in the study). These individuals are frequently at risk for inflammation-related illness. The researchers note that their findings are consistent with high rates of depressive disorders in persons with inflammatory disorders. They cite evidence that experimental activation of inflammatory signaling induces feelings of social withdrawal, depressed mood, and anhedonia. The researchers cautiously report that circulating levels of inflammatory markers rise with age even in healthy individuals, and the proportion of persons with elevated levels of IL-6 rises markedly among persons older than seventy years, increasing the risk of inflammation related disorders (e.g. cardiovascular disease and heart failure, cancer, Alzheimer’s, related neurodegenerative diseases, metabolic alterations, and diabetes). ^[xiii]

Generalizing on this research, a small set of practices such as receiving empathy, meditation (mindfulness), yogic meditation, and Tai Chi, promote well-being by reducing inflammation. These practices are not reducible to empathy (or vice versa), but they all share one single, common factor: reduced inflammation. These anti-inflammatory interventions have been shown to make a profound difference in controlled experiments, evidence-based research, and peer-reviewed publications. Empathy is at the top of my list, but is not the only item on it. Empathy along with mindfulness (a form of meditation), Yoga, Tai Chi, spending time in a sensory deprivation tank (not otherwise discussed here), and certain naturally occurring steroids, need to be better known as interventions that reduce inflammation and restore homeostatic equilibrium to the body according to evidence based research.^[xiv]

In summary, when bacteria attack the human body, the body’s immune system mounts an inflammatory defense that sends macrophages to the site of the attack and causes “sickness behavior” in the person. The infected person takes to bed, sleeps either too much or too little, has no appetite (or too much appetite), experiences low energy, possibly has a fever, including the “blahs,” body aches, and flu-like symptoms. This response has evolved over millions of years, and is basically healthy as the body conserves its energy and fights off the infection using its natural immune response. 

Now fast forward to modern times. This natural response did not envision the stresses of modern life back when we were short stature, proto-humanoids inhabiting the Serengeti Plain and defending ourselves against large predators. Basically, the body responds in the same way to the chronic stressors of modern life—the boss at work is a bully, the mortgage is over-due, the children are acting out, the spouse is having a midlife crisis—and the result is “sickness behavior”—many of the symptoms of which resemble clinical depression—but there is no infection, just inflammation. The inflammation becomes chronic and the body loses its sensitivity to naturally occurring anti-inflammatory hormones, which would ordinarily kick in to “down regulate” the inflammation after a few days. Peer reviewed papers demonstrate that interventions such as empathy reduce biological markers of inflammation and restore equilibrium. This is also a metaphor, though not merely that. When an angry—“inflamed”—person is listened to empathically—is given a “good listening” as I like to say—the person frequently calms down and regains his equilibrium. Empathy migrates onto the short list of inflammation reducing interventions. The compelling conclusion is that empathy is good for your well-being. 

Miracle drug

This entire blog post might have been entitled “Miracle Drug,” except that I have been “scooped” by Stephen Trzeciak, MD, and Anthony Mazzarelli, MD, in their similarly titled Wonder Drug.^[xv] The rhetorical trick is that the reader is expecting to hear about a “breakthrough” psychopharmaceutical product such as Peter Kramer’s Listening to Prozac or a so-called third-generation anti-psychotic medication such as aripiprazole (“Abilify”).^[xvi] Instead the reader hears about “empathy” and a set of empathically-related phenomena such as compassion, altruism, charitable actions, and being helpful to other people in ways large and small. 

The point is that getting a good listening—a description of empathic receptivity—is a powerful intervention and one with significantly fewer side effects than a chemical compound. The point is that, as argued by evidence-based research cited in this blog post, that acts of empathic listening and responsiveness set in motion biological processes that reduce the quantity of stress related chemicals in the body, and do so “naturally,” i.e., without swallowing pills produced by pharmaceutical companies. These entrained biological processes, in turn, have results and outcomes that cause the person to feel better. The person’s vitality, strength, energy, and aliveness are expanded and enhanced. The reasons the person feels better are many, and the reasons vary according to the description that one gives of the intervention. The person feels better because he or she is no longer alone. 

The isolation is broken by getting a good listening. The individual feels understood and sees the possibility of accomplishment, purposeful engagement, and getting what he or she wanted where previously there had been isolation and frustration. The person experiences expanded dignity, less emotional conflict, and a certain peace of mind, because the individual gets the recognition and dignity which had been missing in the individual’s life and for which the individual had been hungry. The individual gets empathy and is able to breathe again, because, the individual was being suffocated by stress, and empathy is like a breath of fresh air. Heinz Kohut famously wrote that empathy oxygen for the soul—without empathy in the individual’s life, the person is going to suffocate emotionally and exist without vitality, strength, energy, and aliveness.^[xvii]

The person whose upbringing is empathy-deprived is going to experience human relations as being on a negative continuum between an emotional Zombie and a roller-coaster of disregulated emotions and behavior. This already takes matters in the direction of another level of discourse, biology versus interpersonal community, though (as far as I know) Kohut never commented in writing on the neurological, endocrinological, or metabolic aspects of empathy. Empathy and a small set of empathically-related phenomena reduces stress and the chemicals in the blood that cause inflammation. This opens up a different level of description and a different level of experience. 

Trezeciak and Mazzarelli cite literally dozens and dozens of evidence-based, peer-reviewed articles, many published since the first edition of this book, that provide evidence that empathy creates a clearing for compassion, altruism, and kindness, and together these produce behavioral medicine that is good for one’s health and well-being.^[xviii] And these men are medical doctors! At the risk of over-simplification, the underlying mechanism is stress reduction through reduced presence or production of inflammatory agents generated by the body in the face of life stress. 

I hasten to add that there is nothing wrong with consulting with a medical doctor about properly prescribed psychopharmaceutical interventions, indeed it is highly advisable. Heck, if one is really planning on acting on one’s suicidal ideation, one had better take the medicine and live to fight another day. Nevertheless, for numerous less acute encounters with the stresses of everyday life—which can indeed be severe and confronting but nevertheless fall short of major mental illness—signing up for a psychopharmacological intervention can be a deal with the devil. Be sure to read the fine print. Be aware that sometimes the “side effects” are hard to distinguish from the “main action” of the medicine. 

The effects of powerful psychopharmacological agents on the nervous systems, the emotions, and behavior are the subject of detailed evidence-based studies, most of which are highly qualified and conditioned, and it is hard, indeed nearly impossible, to generalize. Your mileage may vary, and note well that “all the usual disclaimers apply.” The one, best take-away recommendation that has severed all professionals well across numerous contexts is: “Don’t hurt yourself!” 

So when one says that an empathic conversation for possibility is less risky and has fewer side effects than psychotropic chemicals, there is truth to it. By having an empathic conversation for possibility, one does not put a lot of drugs into one’s blood stream, the side effects of which (as the warning label on the package says) may be unpredictable, and the metabolic consequences of which are scientifically studied and approved by large governmental organizations, but of which the adverse events are not ruled out (again, as specified by the long list of warnings on the label). Now, as far as I know, people experience respect, dignity, recognition, acknowledgement, disappointment, insults, not oxytocin, serotonin, endorphins, dopamine, or approximately a thousand other neuropeptides. While science can demonstrate the occurrence and influence of such chemicals on mood and behavior—using correlation studies to infer causation—the risk is that the person will casually sacrifice individual autonomy to a medication regimen. 

It is a category mistake—a logical error—to imagine that any narrative about the dynamics of neurotransmitters or neurons discharging can provide a meaningful account of human experience of satisfaction or fulfillment in empathically interacting with another human being. It is not that the neurotransmitter account is wrong. On the contrary, at its own level of discourse, it is necessarily an account of the dynamics of neurotransmitters. However, something significant is missing from that account—the relevance of human empathy to community and interpersonal relations. 

The power of empathy should not be underestimated in comparison to these overtly chemical interventions. Most empathic conversations between adults occur in language and language is a powerful media. A group of mean teenagers bullied one of their peers into suicide using language and social media. To be sure, the victim was already struggling with low self-esteem, and tragically did not know how to use speech acts to ask for the help needed. However, the point about the power of language is that no chemicals, only language, was required by the bad actors. People speaking to other people use speech acts to motivate the Others to do things that occur on a continuum between inspired and foolish. 

In a political context (see Chapter 10 of Lou Agosta, 2024, Empathy Lessons, 2nd Edition, on empathy and politics), written documents such as the Declaration of Independence (1776), the Declaration of the Rights of Man (1789), and the UN Declaration of Human Rights (1948) send fear into the hearts of tyrants everywhere, because they know a single fact, though fragile, is able to counter oceans of political propaganda, which, in turn, is why tyrants and demagogues try to control the news media. Though not about empathy as such, these documents show the power of language in the form of empathic responsiveness and rhetorical empathy^[xix] to make a difference in envisioning expanded flourishing in human relations, which is also a goal of empathic relatedness.

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^[i] Yehuda Pollak and Raz Yirmiya. (2002). Cytokine-induced changes in mood and behaviour: implications for ‘depression due to a general medical condition’, immunotherapy and antidepressive treatment, International Journal of Neuropsychopharmacology, (2002) 5: 389–399. DOI: 10.1017/S14611457020 03152.

^[ii] Segerstrom, Suzanne C. and Gregory E. Miller. (2004). Psychological stress and the human immune system: A meta-analytic study of 30 years of inquiry, Psychol Bulletin. 2004 July; 130(4): 601–630.

^[iii] George M. Slavich and Steven W. Cole. (2013). The emerging field of human social genomics, Clinical Psychol Science, 2013 Jul 1(3): 331–348.

^[iv] Yehuda Pollak and Raz Yirmiya 2002.

^[v] Arthur Ciaramicoli. (2016). The Stress Solution: Using Empathy and Cognitive Behavioral Therapy. Novato, CA: New World Library. “CBT” means “cognitive behavioral therapy.”

^[vi] Segerstrom and Miller 2004.

^[vii] M. Maes. (1995). Evidence for an immune response in major depression: a review and hypothesis, Progress in Neuro-Psychopharmaclogy and Biological Psychiatry 19, 11–38; M. Maes. (1999). Major depression and activation of the inflammatory response system, Advances in Experimental Medicine and Biology 461: 25– 46.

^[viii] Mohammadreza Hojat, Daniel Z. Louis, Fred W. Markham, Richard Wender, Carol Rabinowitz, and Joseph S. Gonnella. (2011). Physicians’ empathy and clinical outcomes for diabetic patients, Acad Med. Mar 86(3): 359–64. 

DOI: 10.1097ACM.0b013e3182086fe1.

^[ix] Louis Del Canale, V. Maio, X Wang, G Rossi, M. Hojat, and J.S. Gonnella. (2012). The relationship between physician empathy and disease complications: an empirical study of primary care physicians and their diabetic patients in Parma, Italy, Academic Medicine, 2012 87(9): 1243–1249.

^[x] David P. Rakel, Theresa J. Hoeft, Bruce P. Barrett, Betty A. Chewning, Benjamin M. Craig, and Min Niu. (2009). Practitioner empathy and the duration of the common cold, Family Medicine 41(7): 494–501.

^[xi] Thaddeus W.W. Pace, Lobsang Tenzin Negi, Daniel D. Adame, Steven P. Cole, Teresa I. Sivilli, Timothy D. Brown, Michael J. Issa, and Charles L. Raison. (2009). Effect of compassion meditation on neuroendocrine, innate immune and behavioral responses to psychosocial stress, Psychoendocrinology, 2009 Jan 34(1): 87– 98.

^[xii] David S. Black, Steve W. Cole, Michael R. Irwin, Elizabeth Breen, Natalie M. St. Cyr, Nora Nazarian, Dharma S. Khalsa, and Helen Lavretsky. (2013). Yogic meditation reverses NF-kB and IRF-related transcriptome dynamics in leukocytes of family dementia caregivers in a randomized controlled trial, Psychoneuroendocrinology, 2013 March 38(3): 348–355.

^[xiii] Michael R Irwin and Richard Olmstead. (2012). Mitigating Cellular Inflammation in Older Adults: A Randomized Controlled Trial of Tai Chi Chih, American Journal of Geriatric Psychiatry, 2012 September 20(9): 764–722.

^[xiv] M. H. Antoni, Lutgendorf, S. K., and Blomberg, B. (2011). Cognitive-behavioral stress management reverses anxiety-related leukocyte transcriptional dynamics, Biological Psychiatry, 2011, 15: 366–372; David Black, Steve Cole, Michael Irwin et al. (2013); Michael R Irwin and Richard Olmstead, 2012.

^[xv] Stephen Trzeciak and Anthony Mazzarelli. (2022). Wonder Drug: 7 Scientifically Proven Ways That serving Others Is the Best Medicine for Yourself. New York: St Martin’s Press. 

^[xvi] Kramer, Peter. (1993). Listening to Prozac: The Landmark Book about Anti- depressants and the Remaking of the Self. Revised edition. New York: Penguin, 1997. Heinz Kohut. (1977), The Restoration of the Self, International Universities Press: 85, 251.

^[xvii] Heinz Kohut, MD. (1977). The Restoration of the Self, International Universities Press: 85, 251.

^[xviii] Pace, Thaddeus W.W., Lobsang Tenzin Negi, Daniel D. Adame, Steven P. Cole, Teresa I. Sivilli, Timothy D. Brown, Michael J. Issa, and Charles L. Raison. (2009). Effect of compassion meditation on neuroendocrine, innate immune and behavioral responses to psychosocial stress, Psychoendocrinology, 2009, Jan: 34(1): 87–98; Nelson- Coffey S K, Fritz, M M, Lyubomirsky, S, Cole, S W. (2017). Kindness in the blood: A randomized controlled trial of the gene regulatory impact of prosocial behavior. Psychoneuroendocrinology. 2017 July; 81: 8–13; DiSalvo, D. (2009). Forget survival of the Fittest: It is kindness that counts.” Scientific American, Sept 1, 2009; Furman, D, Campisi, J, Berdin, E, et al. (2019). Chronic inflammation in the etiology of disease across the life span. Nat Med. 25 25, 1822–1832 (2019). As I understand matters, the idea that empathic concern creates an opening for altruistic, compassionate action is convincingly argued by C. Danial Batson in a series of experiments including C. Daniel Batson. (2009). These things called empathy Eight related but Distinct Phenomena. In The Social Neuroscience of Empathy, eds. Jean Decety and William Ickes. Cambridge, MA: The MIT Press, 2009: 3–16. 

^[xix] On rhetorical empathy see Lisa Blankenship. (2019). Changing the Subject: A Theory of Rhetorical Empathy. Logan UT: Utah State University Press.  The reader will also encounter rhetorical empathy in Lou Agosta, 2024, Empathy Lessons, 2nd Edition, Chapter 10: Empathy Application: Rhetorical empathy—speaking truth to power in politics. The counter-intuitive thing about empathic responsiveness is that empathy is usually (and properly) regarding as an attitude of listening, but her the active listening becomes articulate and gives back to the Other what the listener heard in being receptive to the Other’s struggle or accomplishment. The speaking occurs in such a way that it includes the listening of the recipient, in other words, incorporates where the Other is situated affectively, ethically, cognitively, and/or spiritually, depending on the context.

Image credit: William-Adolphe Bouguereau (1825-1905) – At the Edge of the Brook (1879) thanks to WikiMedia Commons: Pubic Domain

URL: https://louagosta.com/2026/10/08/conclusion-part-3-empathy-as-spa-treatment-for-the-soul-connecting-the-dots/

(c) Lou Agosta, PhD, and the Chicago Empathy Project