Depression can can come from the most unexpected places. Take Eva. She was a young, healthy, highly intelligent woman at the outset of her career after years of schooling. Her positive energy and vibrant smile always lit up the room and brought lightness to all that she came across. 

She had a genuine authenticity about her – passionate about all that she pursued and it was apparent in her actions. She exuded a confidence and certainty about herself that inspired others to pursue their dreams. She worked hard and never let mistakes stand in the way of her future goals, taking each one and using it as a lesson to grow. In her eyes, failure was part of the equation to success. Yes, Eva seemed to have it all, the work ethic and determination to succeed in a male-dominated business world and the love and compassion that would undoubtedly make her an incredible mother one day.

Despite all of this, underneath it all, Eva struggled with some dark rooted feelings of sadness.

For most of her life, she had masked them, as she redirected this energy to push herself in her academic and professional endeavors. Yet, even so, there were definite periods during which the feelings would become nearly unbearable to the extent that she would not be able to get out of bed. Though for the most part, she had the capacity to force herself to go through the motions, during its peak, she felt hollow and empty. Apathetic about it all…a numbness that stole the simple joys of life away and made it seem like a never-ending tunnel of darkness. Deep down, she was in pain; the kind of pain that at times would cause her to weep endlessly for no apparent reason. She’d wake up crying and fall asleep crying, with a sense of hopelessness that made her question whether to continue living.

Eva’s story is not uncommon. Like many others walking around us, Eva hid her depression from the outside world, only to suffer internally with little faith that things would ever change, that she’d actually be as happy as she pretended to be. While therapy helped her to a degree, she was one of the countless individuals who do not respond to antidepressant medications.

According to the World Health Organization, upwards of 350 million individuals are currently living with depression. What’s even more alarming is that of that total, only one third respond to the traditional pharmaceutical treatments (i.e. SSRIs). More people are being prescribed antidepressants than should be, and the use of these drugs are not without some degree of risk.

The gravity of these statistics lends itself to the importance of understanding what biological factors contribute to depression and whether there is an alternative solution to this worldwide epidemic…to understand, let’s turn our attention to a major problem that underpins much of modern disease: chronic, systemic, inflammation.

Inflammation… the root of depression?

Inflammation is part of a complex, biological response to injury that involves the activation of the immune system. While inflammation is a normal and healthy response, an exaggerated and prolonged response can be exacerbated as a result of lifestyle factors including: obesity, poor nutrition, a sedentary/inactive lifestyle, poor sleep habits, social stress, environmental pollutants, UV radiation, etc. When this takes place, the excessive inflammatory response results in the body’s release of what are known as cytokines (small, cell-signaling, protein molecules). In turn, the heightened level of cytokines promote a state of systemic inflammation, which has been shown to have detrimental consequences on the brain as well as other tissues.

Think about the common cold symptoms, sneezing, coughing, runny nose and then those symptoms that prompt you to stay in bed, including fatigue, apathy, withdrawal, reduced attention and focus, changes in sleep patterns, loss of appetite, and enhanced pain perception; together, these symptoms, termed “sickness behavior” are initiated by inflammatory markers and strongly coincide with depressive symptoms.

In fact, numerous double-blind, placebo-controlled studies further validate the claim that heightened levels of cytokines and inflammatory markers are linked to symptoms present in depressed patients. In one study, healthy individuals were injected with either lipo-polysaccharide, interferon Gamma, or a placebo, both of which cause an increase in proinflammatory levels of cytokines interleukin-6 (IL-6) and tumor necrosis factor – a (TNF- a). For both experimental groups, an immediate increase in depressive symptoms, including feelings of social disconnection, anhedonia (inability to experience pleasure from activities which use to be pleasurable), and anxiety, was associated with the peak of the proinflammatory response. Similar results were found in animal studies, where injecting rats with interleukin-1a (IL-1a) and TNF-a resulted in sickness behavior (mimicking depressive symptoms) – with significantly higher levels being associated with greater symptom severity. Interestingly, increased inflammatory markers were found among antidepressant nonresponders more often than those who responded to conventional pharmaceutical treatment.  

Given such powerful evidence, researchers have investigated treatment with anti-inflammatory agents as a key component in alleviating depressive symptoms. In various animal studies, typical behavioral responses to stressors, which overlap sickness behavior and depressive symptoms, were reduced with the direct administration of anti-inflammatory cytokines into the brain. Furthermore, in studies looking at individuals suffering from depression along with autoimmune disorders, or any condition characterized by increased inflammation, treatment with TNf-a antagonists improved the depressive symptoms in the individuals. Thus, the reduction of proinflammatory cytokine levels in the body is highly correlated with overall reduction of symptoms.

While depression continues to be a complex disorder, genetics, nutrition, and environmental stress, amongst other factors, contribute to the mechanism by which the immune system and inflammation can directly affect our brain and in turn, our behavior. This perspective may serve as the beginning of a major paradigm shift in healthcare along with the prevention and treatment of depression, providing hope for those individuals who, for too long, have lived with the devastating reality of depression.

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