The story of depression and the brain began with two common sense ideas.  First, there was idea that there was a problem with the part of the brain that controlled our feelings. Second, a newer idea shifted focus from parts of the brain to the chemical messengers that help different parts of the brain communicate with each other. Currently, scientists believe that that story of depression and the brain is much more complex than those original ideas. The new story paints a picture with many different brain parts organized into whole brain networks and multiple different chemical messengers (not just one).
The “Broken” Brain and Lobotomies. Scientists from the early 1900s believed that “overactive nerves” were responsible for causing depression. To cure depression based on this logic, it was necessary to remove these parts of the brain. Patients received lobotomies which meant that physicians surgically removed parts of their brains.  Lobotomies were relatively common until the late 1960s. Although they are still used today on rare occasions, scientists have developed much better treatments for depression that don’t require brain surgery. 
Serotonin and the “Chemical Imbalance Theory”. The next famous theory of depression and the brain suggested that depression was caused by a “chemical imbalance”. According to this theory, people with depression didn’t have enough serotonin. Serotonin is one of the brain’s chemical messengers or neurotransmitters that is involved in influencing mood, sleep, appetite, and pain. We often hear the logic of this theory in “There is research indicating that depression is related to low levels of serotonin. Antidepressants increase your serotonin levels and can help you get rid of your depression.” Although researchers have since shown this theory does not fully explain how serotonin is related to depression, the chemical imbalance theory that explains depression as problem of low serotonin is still very common.
The “Neural Network” of Depression. Today’s researchers argue that the story of depression and the brain is very complex.  They do not believe that depression is caused by a problem in one single brain region or in the overall levels of one single neurotransmitter.  Instead, they think different brain regions are connected to each other in what are called “neural networks”.  Small problems in each brain region that make up just one part of the network can end up causing big problems when you start to add them all together.  For example, a common neural network described by depression scientists includes three major regions:
• The amygdala, which plays a big part in creating emotional experiences.
• The hippocampus, which plays a big part in storing memories and remembering them.
• The prefrontal cortex, which plays a big part in organizing and making sense of all the information coming into and out of our brains.  It also has the ability to control other parts of the brain by making them become more active or less active.
Scientists are conducting research every day that is helping us understand how small problems in each of these brain regions can add up to cause depression. They are also very interested in how one brain region influences another region through the release of neurotransmitters of all kinds. According to this story, many people with depression have an overactive amygdala and hippocampus which is related to experiencing a lot of memories that have strong emotions attached to them.  An overactive amygdala and hippocampus are associated with too much activation in one part of the prefrontal cortex that combines information from all different parts of the brain into our “sense of self”.  This “sense of self” is how we think and feel about ourselves and when we have too much activation in this network, that picture of our self tends to be more negative than positive. At the same time, a different part of the prefrontal cortex is showing signs of too little activation.  This is a problem because this other part of the prefrontal cortex helps decrease activation in the amygdala and hippocampus, and it is hard to do its job of watching over the amygdala and hippocampus when it is not active enough. Each of these smaller problems all combine together to influence our behavior and there is one of type of behavior that is very common with this pattern of brain activity: rumination. Rumination is the tendency to think about negative things over and over again and is one of the key features of depression.  When people ruminate a lot it becomes very difficult to experience joy, problem-solve effectively, and feel satisfied in our relationships with other people. It then becomes easy to imagine how being trapped inside your head creates a whole bunch of other problems that all contribute to the overall experience of depression. 
To learn more about depression and the brain, check out the resources listed below. Three important findings from research on depression and the brain are:
1. The hippocampus does appear to be smaller in some depressed people, and the hippocampus seems to be decrease in size as the number of depressive episodes increases.
2. Antidepressant medications immediately increase the amount of serotonin in the brain but people taking antidepressants don’t typically feel better until several weeks later.  Several weeks after taking antidepressants, we begin to see an increase in the number of new nerve cells in the hippocampus.
3. Newer treatments that attempt to directly target specific neural networks are being developed.  There is good reason to be optimistic about this approach to treatment, but there is still a lot of work to do in terms of making sure they are safe, effective, and accessible.

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