The Neurobiology of Depression

Depression and the Brain

Unlike an open wound or a cast on a broken leg, we cannot actually see that someone has hypertension (high blood pressure), diabetes, or depression.  We only know we have these illness because of the effects it has on our bodies.  They refer to hypertension as “the silent killer” because you don’t see it or feel it until it’s measured by a blood pressure cuff, or you have damage to your organs including your heart, kidneys, and eyes. Many people don’t know they have diabetes until years after they develop it.  Eventually, left untreated, a person will have damage of their heart, kidneys, eyes, and skin.  Depression can be similar, others do not know that it exists in you because it is not always obvious.

There have been multiple theories about what happens in the brain during depression.  There are really good tools that we have for looking at the function of the brain. There is a type of MRI called a functional MRI or fMRI which can give us an idea of how the brain works. The fMRI is able to track the blood flow to different parts of the brain. We used to believe that when people are depressed that they had a “chemical imbalance” primarily of three different neurotransmitters. These are serotonin, norepinephrine, and dopamine (click on the links for review). The problem is that this hypothesis is perhaps only one small contributing factor in the neurobiology of depression.

Researchers now believe that chronic stress breaks down the connections between the neurons, making them weaker. This would make it much more difficult to get the serotonin, norepinephrine and dopamine to the right places in the brain.  In depression there are five areas of brain that fMRI’s could see differences in between a healthy brain and a depressed brain.

Remember when we talked about anhedonia in the last post? Again, anhedonia is the inability to feel pleasure or a lack of interest in things you would normally enjoy. A part of the brain called the nucleus accumbens has a dysfunction leading to anhedonia in a person with depression. The nucleus accumbens (NAc) is the reward center of the brain. If there is malfunction in the NAc, you can imagine it would take the “fun” out of dysfunction and there would be little pleasure.  In studies, they have shown that people with depressive disorders have reduced response to reward compared to people without depression. 

Another part of the brain that is effected is is called the anterior cingulate which controls empathy, decision making, empathy, and impulse control. When this area of the brain is depressed, it contributes to sadness and cognitive deficits. These deficits can also contribute to impulsive behavior.

In depression, some parts of the brain that are affected are overactive, such as the amygdala and the hypothalamic-pituitary axis (HPA). Recall that when the HPA axis is overactive, cortisol is released into the blood stream. Cortisol reduces the amount of serotonin which as we recall can contribute to further depression. Cortisol also causes the hippocampus to shrink and since the hippocampus is responsible for memory and emotion. You may notice that when people are depressed, they have poor memory and feel down. When people are effectively treated for depression, their hippocampus goes back to its normal size.

Other areas of the brain shrink as well including the prefrontal cortex, the cingulate gyrus, and cerebellum. It is believed, in depression, the prefrontal cortex has a poor connection with other regions.

In depression, some parts of the brain are underactive such as in the prefrontal cortex (PFC).  When the PFC is underactive, this contributes to low motivation, lack of hope and poor appetite (Higgins & George, 2013).

We will talk more about treatment for depression in an upcoming post. When depression is treated, the different regions of the brain communicate more effectively.

What Contributes to Depression?

Genetics contributes to a person’s propensity to depression.  In an article by Harvard Medical School, they write: “Every part of your body, including your brain, is controlled by genes. Genes make proteins that are involved in biological processes. Throughout life, different genes turn on and off, so that — in the best case — they make the right proteins at the right time. But if the genes get it wrong, they can alter your biology in a way that results in your mood becoming unstable. In a person who is genetically vulnerable to depression, any stress (a missed deadline at work or a medical illness, for example) can then push this system off balance.”  There is not just one gene that influences depressive symptoms. There are many.  Because of the genetic component, depression runs in families. A person who’s mother or father or sister or brother has depression, is up to 3% more likely to suffer from depression. Some day, researches hope that depression treatment can be individualized in order to be more effective.

Temperament is also a factor which contributes to depressive disorder. In other words, it’s how you view the world in general.  If you view the world as a frightening place, you will be more likely to become depressed. If you are more withdrawn rather than or engaged in life, you may be more likely to be depressed. If you have a perfectionist view or feel unworthy of being loved, you may be more likely to suffer from major depression.

Stress plays a role in depression. Everyone experiences stressful life events such as the death of a loved one, divorce, or maybe a major illness or injury. Grief and sadness are normal for these events, but it is possible for that normal grief to turn to depression. Again, this may be related to how prone you are genetically to major depression.

Early Trauma such as physical, sexual, or emotional abuse, losing a parent, being in foster care, or not having a bond with a caring adult as a child are all factors that most likely will lead to depression. If you have been reading this blog, you may recall the first post on Worry Versus Anxiety and how our fight, flight, or freeze system is a result of the sympathetic nervous system being activated. Those with high levels of chronic stress have higher levels of ACTH and higher levels of cortisol. These stress hormone in high levels can contribute to depression and anxiety. Stress hormones (such as cortisol) when chronically excreted can contribute to major health problems such as cancer and heart disease. Also, in those who have experienced trauma, physical changes can occur in the brain, making it much more difficult to use higher level thinking provided by the frontal lobe.

What About Seasonal Affective Disorder (SAD)?

Seasonal affective disorder occurs in approximately 2% of people when the weather changes to more dark and cloudy weather. The reason this occurs is because sunlight helps your body to produce serotonin among other neurotransmitters and hormones.  It is typically characterized by anhedonia. If you go back to the previous post about the diagnosis of depression, you can review the other symptoms of depression.

So you know the direction we are headed, I will be posting blogs on the following topics related to depression:

1. Treatment for depression in 2-3 blog posts (including therapy, medications, and commentary and alternative treatments.
2. What does depression feel like?
3. Suicide awareness and what to watch for.
4. Faith and depression

References

Higgins, E.S. & George, M.S. (2013). The neuroscience of clinical psychiatry. The pathophysiology of behavior and mental illness. (3rd ed.). Wolters Kluwer: China.

https://www.health.harvard.edu/mind-and-mood/what-causes-depression