Is Depression A Physical Illness? The Link Between Depressive Symptoms and Brain Changes

Friday, April 18, 2014 by Meg   •   Filed under Depression

According to Dr. Peter Kramer in Against Depression, depression is the "most devastating disease known to humankind”1 (pg 150). It alters both psychological functioning—in the form of emotional issues— as well as physical abilities—in the form of pain, lethargy or other connected ailments. Depression strikes early, often triggered by stress or trauma which leads to “kindling”, as discussed in detail in the last post. 

Understanding where depression comes from, as well as what is happening inside your brain, may help you determine the best way to attack it. The good news is that there are a number of treatment options available. The bad news is that most who have one episode will have another, and each episode tends to be worse than the one before it, particularly in those who forgo therapy.

But why would this be?

How Does Depression Change The Brain? This is Your Brain...This Is Your Brain On Depression

Depression affects brain cells in two major ways:

  1. Neuroplasticity: Depression reduces connections between brain cells often leading to cell death.
  2. Neurogenesis: Depression reduces new cell growth, specifically neurons and glia. The neurons--communication cells--need glia to process waste and protect them from damage from toxins. Glia are the garbage disposals of the brain; without their protection, neurons die and communication in the brain changes. 

Depression essentially reduces how well brain cells can communicate with one another which starves certain types of brain cells while refusing to manufacture any more to replace them. This explains why depressive episodes tend to get worse over time. 

That's definitely a physical problem. So what parts of the brain are affected?

Depression and the Prefrontal Cortex

The prefrontal cortex is involved in decision-making, planning, goal-setting and motivation as well as personality factors. This area of the brain shows pronounced changes with depression, and even thinking sad thoughts has been shown to reduce blood flow to this area. It is no surprise that lack of motivation and trouble making decisions are often a prominent feature in depression. 

But there's more.

Remember those garbage disposal cells, the glia? Kramer notes that glia reduce in number, atrophy (stop working well), enlarge (to compensate for ones not working) or are absent altogether in depressed patients. This is particularly true in the prefrontal cortex, where depressive thoughts seem to reside. Damage is also routinely found in cells that help serotonin and norepinephrine communicate through chemical messengers. And the longer people are depressed, the more damage is found in this part of the brain. 

What does all that mean? 


Too much negative thinking = too much reduced blood flow to the prefrontal cortex=reduction in protective cells = damage to cells involved in communication and mood regulation

According to Kramer, glial cells are the police. Enough of them and you can prevent harm.Their absence may allow damage indirectly by allowing toxins to injure neurons.

So, depression may be a disease of being too prone to damage. Those with an inability to repair the brain cells responsible for mood regulation may be more susceptible to future episodes and negative mood as a result. It's a viscous cycle, because with each episode, you lose more cells that aren't being replaced. 

But depression alters more than the prefrontal cortex. 

Hippocampal Damage With Depressive Symptoms

Other researchers believe that this inability to repair may also alter the way the hippocampus operates, a part of the brain responsible for memory and some emotional function. Robert Sapolsky, author of Stress, the Aging Brain and the Mechanisms of Neuron Death, notes that chronic stress--like that present in depression--leads to an overproduction of hormones--glucocorticoids--which inhibit repair functions in the hippocampus2.

Same deal as in the prefrontal cortex: too much stress hormone, glial cells atrophy and neurons don't communicate as well.

But there's a kicker in the hippocampus, because it is responsible for sending out "Stop" signals to the part of the brain that releases cortico-releasing factor, the chemical that tells the adrenals to pump out more stress hormones. If the cells in the hippocampus can't communicate, they can't get the adrenal glands to stop pumping out those hormones, which leads to more cell death when those hormones attack vulnerable neurons. This may be why researchers have found enlarged adrenals in depressed patients. 

Sapolsky isn't the only one to find links to the hippocampus. Kramer notes that cell formation in the hippocampus can be inhibited by the isolation common in depression. Even more compelling, research conducted by Yvette Sheline, found that patients with depression had smaller amygdalae and hippocampi that were eight to ten percent smaller than their non-depressed counterparts3. In addition, depressed women had lower scores in verbal memory tests that were correlated with the number of days a woman had been depressed, likely due to hippocampal damage. 

While earlier hypotheses thought that this hippocampal shrinkage was the result of age, this research is showing that the hippocampus shrinks in direct relation to the number of days a woman has been depressed.

That's major. It's also a major argument for treating depression as a physical disease as opposed to a purely psychological one.

Self-Maintaining Cycles of Depression

So, all those changes to the prefrontal cortex, all that hippocampal shrinkage, those are clearly physical. At the same time--often due directly to these changes--we have a set of depressive personality traits that may attract additional environmental risk factors, further deepening those cycles. 

For example, statistics find that depression can lead to:

Which can all lead to:

  • Higher divorce rates
  • Higher risk for adverse life events
  • Health issues

Which in turn:

  • Triggers additional depression, usually at a lower threshold with each episode because of the damage already present in the brain 

...and repeat

Stopping the Cycle: Ways to Treat Depression

Kramer believes that the most effective way to treat depression is to address the brain systems themselves. But how?

Medications For Depression

This one is tricky. While I am not a pill-pusher as a rule, there are illnesses that require pharmacological intervention, at least in the beginning. Depression is often--though not always--a situation where physical and chemical issues in the brain eventually trigger the emotions in a way that is more complicated than "negative thinking," though that certainly plays a role.

Because of all the different factors and brain structures involved in the depression cycle, there are a number of pharmacological treatments for depression. However, depending on specific brain makeup at the time, patients may only respond to one or two of a wide variety of drugs. Instead of going over all of them, there is a list of common depression medications here, along with whether they are prescribed on label (with clinical trials to back their effectiveness) or off label (drugs prescribed for depression without trials to back up that they work for this purpose). 

Please see a psychiatrist for medication intervention as opposed to a general practitioner. They will be the most able to give an accurate diagnosis as well as properly monitor medications.

Serotonin and Brain Repair

While serotonin was once thought to be the end-all-be-all of depression, there are many medications that change depressive symptoms which speaks to Kramer's bigger issue of brain degeneration and resiliency factors as opposed to simple "one chemical fixes".  

Instead of improving mood directly, serotonin may act more precisely on the resiliency of the brain by protecting neurons and allowing the brain to repair. 

This is reinforced by studies which indicate that Prozac may increase cell growth in the hippocampus and have a protective effect against further degeneration4. This study noted that antidepressants in general may be protective in the brain.

Due to this restorative effect, Kramer notes in Listening to Prozac that Prozac allows people to have the chemical makeup of someone who has less sadness and a less troubled past5

But even Kramer notes that medications are not a magic solution, often because continuing them indefinitely can have consequences on other organ systems. Instead, Kramer notes that drugs work best when take in conjunction with psychotherapy, not as a stand alone1, 5. Instead of simply changing chemical makeup, medications may allow the brain to heal enough for therapy techniques to finally take, so that patients can fare better when the medications are discontinued. 

Therapy As A Treatment For Depression

Psychotherapy has long been a standard treatment for depression, and patients generally fare as well as those on medications. Cognitive behavioral therapy in particular also provides concrete methods for changing thought patterns which can help increase blood flow to the prefrontal cortex and hippocampus (see above), thereby assisting with brain healing in a physical way. Kramer notes that the high response rate to therapy suggests that this may be an additional path for healing brain systems that are injured during depressive episodes. 

Therapy may also work from an evolutionary perspective by fostering connection and avoiding isolation—a trigger for all manner of psychological issues—in addition to helping to regulate brain chemicals through this connection. There is a reason that depressed people with support do better, and why a lack of support can trigger depression all by itself. Closeness and support matter. Without it, we expect to die, as we would have on the savannah. 

Humans did not evolve to be alone.

Can Diet Cause Depression?

It is well known that processed foods can trigger or exacerbate—make worse— depressive symptoms. In one recent study, 3486 participants were examined for links between overall diet and depression. They found that those who ate whole food diets—like fresh fruits, vegetables and fish had significantly less depression when compared to those who ate processed foods—like sweetened desserts, fried foods, refined grains and processed meats6. This suggests that these foods may have the ability to alter the way chemicals are processed by the body, including neurotransmitters in the brain, or may add additional chemicals which interact with resilience factors such as the processing and disposing of toxins, toxins which eventually lead to cell death.  

Similar links have been found in processed drinks. Soda, diet soda and fruit punch have been found to increase depression rates thirty to thirty-eight percent, with even higher risks for the diet variety7. In contrast, this same study found that coffee is a neurostimulant, and tends to reduce depression. From what we know about depression and brain resilience, it makes sense that more natural stimulants like coffee or green tea would reduce depression due to this regenerative effect. 

But keep in mind: diets need time to work. Depending on the level of damage already present, and the amount of chemicals gumming up the works, medications and talk therapies will likely be needed as well, not only to speed the process of restoring neurotransmitter function, but also to assist in learning new ways to cope with learned behavior patterns. 

Other Experimental Treatments for Depression “In The Works"

Alternative medicine has spurned enough new therapies as to require its own series of posts; it simply can't be done justice here (but stay tuned). There are also new pharmacological treatments currently under investigation, including drugs that would block CRF (the chemical that triggers the adrenals to pump out stress hormones)1. Unfortunately, as of yet, the side effect profiles are far too scary, though this may change in time.

Sapolsky is working on genetically engineering cells that produce protectant factors under stress instead of damage. But genetic engineering is a hot button topic for many reasons, one being the higher potential for cancers with introduction of foreign cells, so this treatment won't be available any time soon.

There are also experimental treatments such as DBS (Deep Brain Stimulation) where an electrode is inserted into the brain to turn off specific areas. One such hot spot is the subgenual cingulate gyrus, an area that can lower dopamine transmission in other areas of the brain, leading to depression when it is stuck in the on position. However, such procedures may carry high risks and are not currently FDA approved for the treatment of depression.  

Mind Over Matter Over Mind

This discussion of depression is an illustration of how the physical systems in the body alter the emotional systems and back again. Depression is a physical illness: not only of mind but of body as well, one that degenerates over time reliably like medical conditions. 

So should it be treated as such with all the requisite insurance benefits that we subscribe to, say, diabetes? 

Kramer's is only one theory in the progression of depression but I think it's a pretty good argument for treating it like a disease as opposed to being a mental health condition, which currently makes is subject to refusal of coverage by insurance companies. 

Aside from the insurance issue, seeing depression as a medical condition may help to destigmatize the illness itself, encouraging those who suffer to get help for it. Medical issues like diabetes and high blood pressure don't carry the stigma that psychological conditions carry. Someone with high blood pressure is not seen as “weak" or "overemotional". Nor should we see those who suffer with depression in this way. 

Don't believe "It's all in your head." It isn't. 

It's in your brain, in your adrenal glands, in your chemical makeup. It can be fixed. But it is not something to tackle alone. 

Related Posts:


Topic-Relevant Resources

Listening to Prozac: The Landmark Book About Antidepressants and the Remaking of the Self, Revised Edition
Psychiatrist Peter Kramer discusses the implications of preferred personality on mental health along with the evolution of Prozac as a preferred treatment for undesired traits.

Against Depression
Detailed explanations of the systems involved in depression along with personal stories of success from psychiatrist Peter Kramer.

Stress, the Aging Brain, and the Mechanisms of Neuron Death (Bradford Books)
Primatologist/biologist Robert Sapolsky on the brain mechanisms involved in stress regulation.

Mindsight: The New Science of Personal Transformation
New techniques for mindfully altering the wiring of your own brain, leading to increased happiness.

The PTSD Workbook: Simple, Effective Techniques for Overcoming Traumatic Stress Symptoms
A useful tool in exploring personal trauma, with an emphasis on healing.