The Purpose for Depression

Photo credit: Callie Gibson

Photo credit: Callie Gibson

If you haven’t ready my article titled “Adaptation and disease: two sides of the same coin,” I highly suggest you head over to our pathology section and check that out before proceeding with this article. That article describes a framework for understanding why disease arises in the first place.

To sum it up concisely, there is growing evidence in many different pathologies that diseases actually arise as an adaptation by the body that has some protective affect in one regard, but eventually becomes maladaptive in some way: either in a different compartment of the body or at a later time point. For example, sickle cell disease is protective against certain malaria infections, but is also detrimental to blood carrying capacity (and many other symptoms associated with the disorder that stem from changes in hemoglobin structure).

This example is easy to understand, however, more evidence is accumulating that shows that even complex and multifactorial diseases like type 2 diabetes could be a result of the bodies protective adaptations against rapid metabolic collapse in the heart and brain and certain genes associated with disorders like type 1 diabetes may actually be protective against infectious agents.

As another example of disease and adaptation, patients with Huntington’s disease have been shown to be 80% less likely to get cancer than patients that do not suffer from the disease. Credit: EMBO Reports

As another example of disease and adaptation, patients with Huntington’s disease have been shown to be 80% less likely to get cancer than patients that do not suffer from the disease. Credit: EMBO Reports

Understanding why diseases arise in the first place can help us not only understand their pathophysiology, but also understand the most effective ways to reduce all cause mortality, minimize disease burden, and maximize quality of life. If this theory applies to every somatic disease that we know of, then why couldn’t it apply to the “S” in the VITAMINS acronym; psychiatric (see the “Introduction to pathology: get your dose of VITAMINS” article for more on the acronym). The question remains, could we boost our understanding and treatment of poorly understood, yet rampant diseases like major depressive disorder and general anxiety disorder by understanding adaptations made by the body with initial protective affects?

For the purposes of brevity and scope, we’ll focus on major depressive disorder (MDD) for the rest of the article. MDD is thought to affect over 10% of the world population and is the number one cause of disability worldwide. MDD is traditionally a psychiatric disorder consisting of multifaceted changes in mood, cognition, motor functions, and motivation.

In the past, the pathophysiology of depression has been based on the “catecholamine hypothesis,” which states that disruption in a group of hormones called catecholamines (serotonin, norepinephrine, dopamine, etc.) leads to onset of the aforementioned symptoms. While this theory has led to some success in treatment, most studies show only about a 30% remission in symptoms with pharmacotherapy using selective serotonin reuptake inhibitors (SSRI’s) or combination selective norepinephrine reuptake inhibitors (SNRI’s) and cognitive behavioral therapy (CBT).

Some researchers think depression and anxiety may carry some psychological benefit, in that it makes patients more cautious and therefore preserve their safety. Photo credit: Nick Agus Arya

Some researchers think depression and anxiety may carry some psychological benefit, in that it makes patients more cautious and therefore preserve their safety. Photo credit: Nick Agus Arya

But how can we frame an abstract and subtle psychological disease in the frame of evolution? For quite some time now (at least since the 90s) psychologists have been proposing depression (and anxiety in some cases) as a psychological adaptation with certain competitive adaptations. In 2000, Randolph Nesse published a review tallying the evidence for and against depression as an adaptation to particular situations. By this time, many theories had been presented including depression being an adaptation for submitting to dominant figures in social hierarchy, preserving crucial resources (due to side effects of nausea, hypersomnia, inactivity, etc.), or deterring one from activities that would cause damage to the body. While many theories were presented in this review, Dr. Nesse’s ultimate conclusion was that there wasn’t enough evidence to say for certain either way.

On the contrary, other groups have suggested that MDD is purely maladaptive with no competitive advantage. This opposing viewpoint would suggest that low mood and subsequent depression is a result of the extremes of a given behavioral trait that results in a non-adaptive extreme and pervasive low mood. However, many agree that this hypothesis is insufficient to explain the high incidence of depression.

In the middle of the two theories that depression is purely adaptive for fitness advantages and depression being a purely pathological maladaptive extreme of normal behavioral traits lies the idea that low mood begins with adaptive mechanisms that dysfunction due to random environmental inputs leading to a persistent and extreme form of the initial adaptation (i.e. depression).

The latter model, developed by Dr. Pete Trimmer suggests that failed behavior, whether it be in a favorable or unfavorable environment, leads to a higher likelihood of declining to pursue activity in a given situation. An individual who is so “unlucky” that their behavior fails multiple times in a row due to random outcome of some events even in favorable environments is likely to stop trying, thus leading to maladaptive inactivity. This comprehensive model includes characteristics of both evolutionary adaptions along with the occurrence of individual life events into the development of depression.

According to one model, those people presented with a series of unlucky life circumstances may be more inclined to lose motivation to keep trying, leading to depression. In this example, depression is just a matter of circumstance. Photo credit: Chris Liverani

According to one model, those people presented with a series of unlucky life circumstances may be more inclined to lose motivation to keep trying, leading to depression. In this example, depression is just a matter of circumstance. Photo credit: Chris Liverani

The inclusive nature of the Trimmer theory has caused it to gain a lot of momentum in the psychology literature in recent years. However, like anything in science, there is not quite enough evidence to say for certain that this theory is correct. Perhaps the most difficult aspect of studying psychiatric disorders is their variability in individual experience and subtle somatic manifestations, making objective characterization a major challenge.

In my personal opinion, I believe that the advent of advanced imaging techniques such as glucose metabolism PET and eventually fMRI in patients with depression will lead to a breakdown of what we now refer to as “major depressive disorder” into several distinct neurobiological and symptomatic subtypes, each with a unique yet distinct set of characteristics that can be more easily incorporated into an evolutionary framework.

Functional MRI imaging, or fMRI, can detect changes in brain activity based on blood flow in the brain, and is becoming a powerful tool for visually describing the variations in brain function. Credit: PsychologySoftwareTools

Functional MRI imaging, or fMRI, can detect changes in brain activity based on blood flow in the brain, and is becoming a powerful tool for visually describing the variations in brain function. Credit: PsychologySoftwareTools

In fact, one group at Emory University led by Helen Mayberg is already attempting to do just that. By using advanced imaging techniques, they are able to associate certain symptomatic subtypes of major depressive disorder with neurological biomarkers and even predict who will respond to antidepressants and who won’t! These studies are propelling the field of psychiatry towards more personalizable medicine and are helping us to understand the hard physiology of elusive psychological disorders. Keep your eyes open for another article discussing these findings!

So, does the body have a purpose for depression in the same way evolution used protection against malaria as a reason to create sickle cell anemia? In short, the answer is unclear at this point in time. There are a significant amount of people who believe that depression is a purely adaptive behavior and even more people who believe the initial stages of low mood and depression provide a competitive advantage, but due to random environmental inputs (i.e. experience) these behavioral adaptations become pervasive, debilitating, and maladaptive.

Much in the same way that people believe humans developed anxiety to avoid potentially threatening situations, there is a high possibility that low mood and milder forms of depression are actually helpful to the individual. But the question remains, how did something that potentially began as an adaptation end up being the most common cause of disability world wide?

-Daniel


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