The Chronic Illness-Depression Connection

All work and no play makes Jill a dull girl...but it also renders her susceptible to dysfunction in her hypothalamic-pituitary-adrenal-thyroid-gonadal axis, dysregulations in digestion and immunostasis, and vulnerability to infections—which was the case with me recently.

A confluence of factors, including sleep disruption, escalating stress, and a higher intake of refined sugar intersected to compromise my immune status and I recently came down with a recalcitrant upper respiratory infection—which hung on through much of my vacation in California.

I recognized changes in my executive function—those cortical brain functions that coordinate higher-order neurological functions including organization, decision-making, problem-solving, synthesis and assimilation of information, abstract thinking, perceptual experience, self-awareness, planning, word recall, mood regulation, and memory retrieval.

Alongside the normal physiological expressions of a cold, I was more forgetful, constantly losing my phone or my keys or misplacing my possessions, my proprioception was poor, and my ability to focus, concentrate, and direct my attention to even simple tasks at hand was severely interrupted.

The first step of managing these symptoms, however, is to identify them for what they are—compensatory adaptations undertaken by your body to protect and heal you.

Falling ill not only has the potential to disturb homeodynamics, but it can also derail our cognition, mood, and executive function, which was the case for me.

When we are sick, either acutely with a pathogenic infection or long-term with an autoimmune disorder or other chronic malady, we tend to feel depressed and exhibit certain telltale symptoms that can be classified as sickness behavior.

Sickness behavior is the manifestation of a central motivational state which restructures the priorities of the organism to cope with an infectious or inflammatory threat.

Inflammatory intercellular signaling molecules known as cytokines, released peripherally as a result of an ongoing pathophysiological disease state or an infection, are capable of penetrating the blood brain barrier and infiltrating the central nervous system.

These pro-inflammatory messengers, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), permeate the brain tissue and initiate inflammatory cascades in such a way as to produce anxiety, depression, and characteristic behaviors exhibited by sick persons including disturbances in sleep and appetite, social withdrawal, and lethargy.

They are communicated to the brain via both a fast transmission pathway via afferent nerves innervating the body site of inflammation as well as a more protracted transmission pathway entailing cytokines derived from the choroid plexus and circumventricular organs which diffuse into the brain parenchyma via volumetric transmission.

During infection, there are also cytokines produced within the central nervous system which act on receptors identical to those expressed on the surface of innate immune cells which perpetuate inflammatory cascades and negatively impact learning and memory.

Sickness behavior, like all physiological processes, does not happen by mistake. It represents an evolutionary adaptation that serves to engender self-preservation in the face of a challenge to homeostasis.

It protects both us and the tribe. The depression that it creates leads to self-imposed social alienation and a forced slowing of daily activities as a result of fatigue, both attempts by our body to generate an environment conducive to rest, recovery, regeneration, and inhibition of contagion transmission.

Sickness behavior, then, is a highly orchestrated process undertaken by the body with the intention of getting you well.

We shift into a state of self-preservation and a lower energetic vibration at the expense of sexual and social drive, tribal affiliations, and community bonding for the sake of health—as the needs of the individual to survive the illness episode come to circumvent the normal human drive towards reproduction and transmission of our genes to the next generation.

As articulated by Dantzer, subjective signs of sickness behavior, including malaise, musculoskeletal pain, lassitude, fatigue, numbness, temperature and appetite dysregulation, low libido, as well as social isolation, are commonly ignored by physicians:

“They are considered uncomfortable, but banal, components of the pathogen-induced debilitation process that affects sick individuals.

This simplistic view has turned out to be incorrect. The psychologic and behavioral components of sickness represent, together with fever response and associated neuroendocrine changes, a highly organized strategy of the organism to fight infection” (Dantzer, 2006).

However, these cardinal behaviors of sickness behavior are likewise mobilized during chronic, long-latency illnesses, degenerative states, and autoimmune disease, and can interfere with healing, productivity, and quality of life when they manifest on a long-term basis.

By reframing the depression accompanying chronic illness through this lens, we can discover solace in the fact that nothing our body does is an accident. The coughing, sneezing, and runny nose that accompany a respiratory virus, for instance, serve to expel the invading pathogen, whereas the fever your body produces in response to pathogenic invasion render the body inhospitable to virulent microorganisms.

Even psychiatric symptoms serve a purpose and represent your body’s concerted effort to protect you and to put you into self-survival mode in order to keep you alive and return you to homeodynamics.

By addressing the inflammatory fires that perpetuate the cycle of cytokine-induced sickness behavior, through interventions targeted at gut health, oxidative stress, dietary sensitivities, hormonal imbalances, parasympathetic tone deficiency, and evolutionary mismatch, we can remediate the underlying causes of depression while also attenuating the pathophysiological processes behind chronic illness.

By viewing illness through this paradigm, we can come to appreciate the innate wisdom of the divine vessel that is our body—to lean into symptoms rather than suppressing them with pharmaceutical cocktails—and to express gratitude for our symptoms as an opportunity afforded by our bodies to recuperate.


Dantzer, R. (2001). Cytokine-induced sickness behavior: where do we stand? Brain Behavior & Immunology, 15(1), 7-24.

Dantzer, R. (2004). Cytokine-induced sickness behaviour: a neuroimmune response to activation of innate immunity. European Journal of Pharmacology, 500(1-3), 399-411.

Dantzer, R. (2006). Cytokine, Sickness Behavior, and Depression. Clinical Neurology, 24(3), 441-460.

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