The Relationship Between Depression and Stress

Hippocrates wrote that we are all beset by disturbing forces that upset our balance (1). Fortunately, there are restorative forces that can re-establish balance. Galen called these Vis Medicatrix Naturae, the healing forces of nature (1, 2). We now call the disturbing forces stressors, the balance homeostasis, and the healing forces adaptive responses (3).

Stressors are imminent or perceived challenges to balance or homeostasis (4). Stress is almost always accompanied by increased vigilance and anxiety. The response is strongest when the stressor is highly unpleasant and uncontrollable.

Like other responses, such as the immune response, the stress system is essential for survival. The immune system can also run awry and lead to autoimmune disease (5), where the immune system attacks our own tissues. In depression, a wayward stress system attacks the brain foremost, as well as multiple tissues throughout the body, leading to depression (6, 7).

The Normal Stress Response

Let’s consider a normal stress response. Imagine that a small group of individuals is hiking in the woods as night approaches. A wildfire is spreading rapidly nearby. The hikers are anxious, highly vigilant, and focused entirely on the threat. Their collective mood fixes in a distressed and fearful mode. To keep them focused, the stress response lowers their distractibility. In particular, they aren’t drawn to pleasurable stimuli. During this threatening situation, they won’t be distracted by food, sleep, sex, or a pretty scene (8).

Our hikers’ brains push the pause button on complex thinking about anything beyond finding their way back to their base safely. Physical responses accompany their behavioral responses. Their hearts race, and their blood pressure increases. Cortisol and adrenalin levels rise precipitously. Inflammation occurs during the normal stress response to prepare for a potential injury. Blood clotting is activated to prepare for a possible hemorrhage. Blood sugar rises to provide extra fuel for their stressed brains. Notably, and regrettably, these behavioral and physiological responses also occur during psychological stressors such as public speaking (8).

The presence of phenomena such as inflammation and increased blood clotting as a routine component of almost any stress response is an important new concept that helps explain why chronic stress and melancholic depression can have such devastating consequences (8).

How Did Increased Inflammation, Blood Clotting, and Blood Sugar Levels Get Folded Into Our Normal Stress Response?

Our evolutionary and biological roots provide a possible answer. In the past, major stressors consisted of being hunted and competing for a mate. The risk of injury in each of these contexts was very great. Thus, the connection between the perception of stress or danger (9) activated responses of the inflammatory and coagulation systems and signaled blood sugars to rise. Their legacy for those of us in the present, when they are irrelevant to most of our stress responses, is a significant burden.

The Hikers Reach Home Base

When the hikers reach their home base, most feel much better and can think more clearly. They can enjoy a beautiful scene, and their heart rates, blood pressures, immune systems, blood clotting systems, and blood sugar levels return to normal. In one individual, the stress response did not resolve but evolved into a severe case of melancholia (8).

How Does the Stress Response Morph Into a Melancholic Depression?

The defining behavioral characteristics of both stress and melancholia consist of fear, anxiety, and alarm. As noted in an earlier paper in Psychology Today, melancholia contradicts the word “depression” in that it is often a state of increased arousal and anxiety, often directed at the self. Individuals with melancholia are often bombarded by negatively charged emotional memories of failure and loss that significantly contribute to the depressed state. They lose the capacity to experience pleasure, experience decreased appetite and weight loss, have insomnia, and lose interest in sex.

During stress, sufficient anxiety promotes substantial efforts to avoid being hurt without interfering with effective functioning. In melancholic depression, fear, anxiety, and alarm can be profoundly greater than during stress, produce anguish and hopelessness, and interfere with the capacity to fight off depression (8).

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As noted above, during stress, cognition shifts from complex reasoning to automatic, instinctual actions or actions that had previously worked in dangerous situations. In melancholia, cognition is often limited to obsessive, ruminative preoccupations regarding the deficiencies of the self. Concentration is impaired, and overall cognitive function suffers (8).

During stress, there is a modest decrease in the capacity to respond to pleasurable stimuli as a means of protecting against unwanted distractions. This does not lead to a demoralization that could interfere with an effective stress response. In melancholia, the decrease in the capacity to anticipate or experience pleasure is pervasive and profound, leading to the incapacity to enjoy anything or remember ever being happy (8).

Additionally, during stress, there is a tendency towards a decreased appetite and a decreased propensity to sleep to allow total focus on the threat at hand. Melancholic patients lose their appetite, which can be life-threatening in the elderly, and have insomnia, most often with early morning awakening.

The inflammation, increased blood clotting, and high blood sugars associated with melancholic depression are likely to contribute to premature coronary artery disease (10), diabetes (11, 12), stroke, and osteoporosis (13) that occur in depression and that shorten lives by 7-10 years, independent of suicide or smoking (14, 15).

It is clear that melancholic depression responds best to a combination of psychotherapy and medication. Patients suffering from melancholic depression need more than relatively infrequent doctor’s visits to manage medication alone. Doctors must also be aware of the depressed patient’s susceptibility to premature systemic illnesses and utilize the medical means available to prevent, treat, or keep these illnesses from progressing. In addition to a battery of medical tests, antidepressants can also neutralize many of the physiological stigmata of depressive illness (14).

Overall, while a normal stress response is highly adaptive, depression represents a distorted, prolonged, pernicious version of a stress response. This is compatible with our knowledge that stress imprints itself on the stress system of the brain, damages or destroys critical tissues, and leads to the clinical and biochemical manifestations of illnesses such as melancholic depression (6, 7, 16, 17). Having this increased understanding of stress response and its impact on depression and overall health brings new and critical advantages in treatment options and efforts today, offering promising paths to wellness for millions.