The Current Context

We live in a world with ample opportunities to learn how to deal with fear.

Sadly, the effects of fear on our physiology can be magnified through non-stop media as fear-provoking situations are not only presented but repeated throughout a 24-hour news cycle. 

The literature describes the negative effects of heightened media consumption during times of conflict. For example, those who increased their news consumption during a time of war affecting their country were 1.6 times more likely to report a symptom of anxiety vs those who did not increase their viewing time or reduced it.^[1]  These symptoms included uncontrolled fear, physiological hyperarousal (increased heart rate, sweating, or irregular breathing), and sleeping difficulties. Recent follow-up research indicates that women and children are most susceptible to the stresses caused by this increased news exposure. It also highlights that many describe watching news during these periods as addictive.^[2] 

Intriguingly, even when someone is living in a relatively low-risk environment, increased consumption of media from a broader context may lead to suffering from fear.  This was observed during a qualitative study composed of interviews of participants from Prince Edward Island, the geography of Canada with the lowest level of COVID-19 exposure at the time.^[3] Participants expressed that media coverage exacerbated their pandemic-related stress, portraying situations worse than reality. They coped by turning to local news and considering the pandemic’s impact on those more severely affected.

Sometimes government messaging seeking to change behavior during a crisis can slip into fear-based messaging.  Again, this became evident in some places during the initial years of the COVID-19 pandemic. Despite previous evidence that fear-based messaging can hinder recovery from the actual harm, emotionally charged messaging intended to catalyze change among the complacent took the form of slogans such as “Don’t Kill Granny.”^[4]  As pointed out by the authors of the previous citation, such messaging is particularly problematic for young people who would lose grandparents during the pandemic due to COVID-19 through no fault of their own.

We do not point to such examples in any effort to minimize the real, excruciating, and unfair suffering caused to many innocent people during war or pandemic, or to suggest that every government effort to encourage responsible behavior is misguided.  Indeed, fear has an important role in helping us decide to stay away from, or at least successfully manage, dangerous situations. But if we are not careful in handling fear-laden crises, including politically charged ones, we may succeed in magnifying and intensifying their impact on our health. We may even contribute to a wind-up cycle of fear that becomes increasingly enticing.

Some Basic Elements of Fear Circuitry

When considering fear, it’s useful to think about the brain circuitry involved, often referred to as the fear circuit. This includes key structures like the medial prefrontal cortex, hippocampus, and amygdala. These areas collaborate to help us form memories of fear so that we can respond to its cues in protective ways, including through activation of the hormonal stress response.^[5],[6]  The elements and functioning of the fear circuit and how fear interacts with other emotions or motivations seems to be exceptionally complex.

One intriguing example is the report above of viewers describing a feeling described as addiction while watching frightening news reports. While it’s still not fully understood why certain types of fear can become appealing, exploring the role of the nucleus accumbens might be beneficial. Recently recognized as part of the fear circuit in animal studies, this brain region could offer insights into this phenomenon. ^[7] Dopamine is a common neurotransmitter in tissue of the nucleus accumbens, being necessary to shape both wanting and fear. Moreover, depending on the environment in which a stimulus is encountered, we might flip our motivation from seeking reward to focusing on fear instead.^[8] 

With evidence accumulating that the affective function of neuronal tissue, and the nucleus accumbens specifically, can switch dynamically depending on context,^[9] and with fear and reward both being sorted out to some degree within tissue that measures on the scale of millimeters and awash with the same neurotransmitter of dopamine,^[10] is it possible that we can indeed come to want fear?  While we don’t know the answer to that question with certainty at present, we feel it is important to raise the question for continued consideration, as the costs of an enticing wind-up of fear both to individual patients and to society as a whole would be significant.

As we consider the potential impact of fear, we turn the balance of our discussion to exploring the effects of fear as a form of stress on our anatomy and physiology, including how fear as a form of stress may be linked to disease through inflammation.  We will also consider how modulation of gut flora may impact connectivity of fear circuitry and fear-based behavior.

Effects of Fear on Our Organism

As a form of stress, fear and its long-term manifestations such as anxiety, may be considered in the context of the three predicated stages of response described by Hans Selye, known as the stages of the General Adaptation Syndrome (GAS)^[11]: the stage of alarm, characterized by adrenal enlargement and increased adrenal secretion, atrophy of the thymus and lymphatic structures, and ulcerations of the GI tract; the stage of resistance, where secretion of cortisol levels are maintained at an increased level to try to cope with the stress; and the stage of exhaustion, where the organism can no longer cope with the unresolved stress and cortisol levels decrease.  An excellent example of a stress that follows this pattern is the stress of infection with SARS-CoV-2,^[12] the pandemic that has undoubtedly also included a great deal of fear.

Is Fear Entwined with Inflammation?

Some of the interesting questions about the stage of resistance as a response to stress of many forms is the potential to develop impaired glucocorticoid signaling and for impaired signaling to lead to an increase in inflammatory burden. Examples of decreased cortisol sensitivity as a response to stress have been reported; for example, a cross-sectional study of Chinese railway dispatchers found that those with higher and medium stress had both higher levels of cortisol and reduced levels of glucocorticoid receptors versus those with lower stress.^[13]  There is also evidence of decreased cortisol sensitivity leading to greater inflammation.  For example, parents facing the chronic threat of children diagnosed with cancer showed an impaired response to anti-inflammatory signals, along with reduced ability for a synthetic glucocorticoid to suppress Interleukin-6 production, in vitro.^[14]  However, the circumstances of impaired glucocorticoid signaling and increased inflammatory burden are not always the same. 

For reasons that are not entirely clear, sometimes cortisol insensitivity may occur even when there is no obvious change in the amount of cortisol secreted.  For example, over a year, even though caregivers of those with cancer showed similar secretion of cortisol to controls, they also showed decreased glucocorticoid sensitivity in vitro, a decrease in the mRNA of anti-inflammatory signaling molecules, and an increase in systemic inflammation as reflected in C-reactive protein.^[15]   Interestingly, increased inflammation can sometimes result from heightened cortisol sensitivity that leads to decreased levels of cortisol. This seems to be the context of glucocorticoid signaling dysfunction in post-traumatic stress disorder (PTSD)^[16] (and perhaps PTSD is not a situation that fits neatly within a stage of resistance but also shares features of the stage of exhaustion).  Whatever the exact scenario, disruption of normal glucocorticoid signaling can favor more significant inflammation.

There are emerging examples of dynamic connections between inflammation, feelings of threat, and some diseases both acute and chronic.  For example, results showed that inflammation induced by low dose lipopolysaccharide in healthy men increased feelings of anxiety and the temporal variance of the amygdala during functional MRI analysis.^[17]  In exploratory analysis of another more chronic context, C-reactive protein was higher in women with what may be viewed as chronic, fear-based conditions of anxiety and/or PTSD when considering symptoms of both conditions together (but not singly).^[18] Further, in a group where most women were suffering with both PTSD and depression (a condition with a more studied link to inflammation^[19]) after suffering a recent traumatic assault, follow-up after a year showed an increase in multiple inflammatory markers, including Interleukin-1 beta, tumor necrosis factor-alpha, and C-reactive protein, versus a control group, even as psychological symptoms improved.^[20] Data shows that C-reactive protein can correlate with symptoms of both depression and PTSD in American soldiers.^[21]

Fear and the Telomere

Another important relationship to consider is the association between threat and telomere length, which may serve as an indicator of cellular aging.^[22]  As reviewed by Alay,^[23] there seems to be a link between shorter telomeres, diseases we associate with aging (for example, cardiovascular disease, Alzheimer’s disease, and type 2 diabetes), and mortality.  In PTSD, though not all studies agree, a view of the collective data in the form of a meta-analysis of 3,851 subjects did find a significant association between PTSD and shortened telomere length, with shortened telomere length being significantly associated with sexual assault and childhood trauma.^[24]  Across a cohort of a nationally representative sample of the Finnish population, there was not an association between telomere length and anxiety; however, among the older portion of the cohort, those 48-87 years old, those with anxiety disorders did have significantly shorter leukocyte telomeres compared to healthy controls.^[25]  The presence of serious or chronic conditions in childhood was the factor that had the greatest association with the shortening of telomere length. 

These studies’ focus on the link between telomere length and childhood trauma is intriguing and prompts us to consider fear’s potential effects across generations. An intriguing study in song sparrows is worth noting in this context. When adult sparrows were exposed to predator sounds, their offspring were leaner and had shorter telomeres compared to controls.^[26]  The authors suggest that in the context of this study the shorter telomeres, indicating poorer physiological condition, may be linked to poorer parental care.  This study shows a potential generational impact of fear on families, emphasizing the importance of considering parents’ and children’s emotional health collectively. 

A Gut Full of Fear

Few perspectives from naturopathy would be complete without highlighting the role of gastrointestinal health, and this work is no exception. Increasingly, the gut-brain axis is becoming appreciated as a diverse, bi-directional system, complete with feedback loops.^[27]  Researchers are beginning to appreciate this system as impacting multiple areas beyond digestion, including affect and motivation.^[28]  In one example of this, colonic motility was directly observed to increase in subjects who perceived a threat to their security, such as being interviewed about a situation of conflict in their lives, or, in a study structure that would not take place today, being falsely led to believe that  a cancerous lesion had been discovered and had been biopsied.^[29]  Considering again our discussion on COVID and the stress of fear related to the pandemic, there is evidence that those with IBS suffered from an increase of symptoms and also reported an increase in social withdrawal due to GI symptoms during a time of COVID lockdown.^[30] 

Certainly, one approach to nourishing the gut is the provision of probiotics.  Thus far, while the literature on the potential of probiotics in ameliorating adverse effects of fear on the gut and brain is small, there is some literature to begin to think about.  One study examined the effect of chronic mild stress on the microbiota and behavior in mice.^[31]  While the study was designed to induce symptoms of despair in the mice and thus serve as a model of depression, some of the forms of chronic, mild stress could be seen as fear-inducing, including restraint, tilting of the cage, and exposure to loud white noise and to a strobe light. That these experiences of chronic stress laced with fear induce despair and symptoms of depression is also an important connection to note. The chronic and unpredictable, mild stress in the experiment led to a reduction in Lactobacillus as well as an increase in behaviors associated with despair (escape behavior).  Supplementing with Lactobacillus reuteri improved this behavior and was also linked to a restoration of normal kynurenine metabolism.

In another mouse study, supplementation with Bifidobacterium reduced the hyperactive stress response induced by separation of mouse pups from their mother. This included decreased corticosterone production and reduced intestinal inflammation.^[32]  Perhaps in the end we will find the brain and gut so connected and impactful on each other that we will understand that we cannot offer complete therapeutic support to one without also supporting the other.

Thoughts on How to Manage Fear and Reduce Its Negative Health Consequences

Addressing coping approaches to fear, we highlight several promising methods. For instance, mindfulness meditation has shown to mitigate chronic inflammation linked to fear-induced diseases. Participants in a three-day mindfulness retreat experienced reduced anxiety and lowered inflammatory markers Interleukin-6 and Interleukin-8, while Interleukin-10, an anti-inflammatory cytokine, increased.^[33] Virtual reality exercise environments have also proven effective in reducing anxiety symptoms, particularly when paired with natural scenes.^[34] Of course, exercise in the beauty of real-world nature has a lot to offer as well.

Additionally, organized religious activities, such as attending services, have been associated with reduced anxiety and depression among university students,^[35] with equal benefits seen in both Catholic Christians and Protestant Christians. Attendance of organized religious services was also associated with significantly reduced prevalence of any anxiety disorder in the last 12 months and over a lifetime in Black Americans.^[36] A rather sizeable systematic review of 28 controlled trials found that recitation of the Holy Quran in multiple settings, including prior to medical procedures, student exams, and athletic performances, was consistently associated with greater reductions in anxiety versus control groups.^[37]  There may be multiple reasons why each of these interventions above prove effective, and we look forward to further research in each area.

Closing Thoughts

Fear gives us a lot to think about.  Though the feeling of fear can stimulate us to protect ourselves, over-activation of fear circuitry may extend beyond alarm to stages of resistance and even exhaustion.  Along the way, sickness of various kinds, associated with inflammation, as well as shorter telomeres, can manifest.  A healthy bowel and associated microbiome are likely important to managing fear-associated pathology, while mindfulness, exercise, and religious involvement, according to one’s belief, may all be helpful approaches to mitigating the adverse effects of unresolved fear.

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Published July 27, 2024