Neurobiology of Major Depressive Disorder

A Brief History in the Diagnosis of Major Depressive Disorder

So let’s get to the meat of this discussion and talk about what we have discovered so far about the “symptom cluster” we call Major Depressive Disorder. Back in the early 1970s when I first entered college, the etiology of depression was a ‘free for all’. Spiritual people said that it was a spiritual issue. Sociologists saw it as a social issue. Psychologists saw it as a psychological issue. And medical people… Well, you get the idea.

In the late 1980s and early 1990s functional MRI scans of the brain became available. These allowed everyone to actually see the measurements of metabolic activity in various areas of a person’s brain under a variety of conditions. Morphometric MRI measured the size of various brain regions, magnetic spectroscopy measured the amount of various chemicals in specific areas, and diffusion tensor imaging measured the density of axonal branching that connected various neuronal trees.

What all of this allowed was the development of the story of what happens in the brain when someone feels unwell, sad, anxious, angry, depressed, and what happens in these same areas when someone feels better or receives help. One would think that this would allow us to have it all figured out! However, there seems to be at least two major issues. Even with all of this technology, individuals remain too variable in many aspects of brain size and activity to accurately say anything about a single individual. Also, our brain is much more complex than anyone could have imagined. Down to the smallest ‘voxel’ we are able to measure there are at least 100,000 neurons providing at least 40 different functions. The brain works in widespread, diffuse systems.

The Neurobiology of Major Depressive Disorder: What We Know Now

So which one of my professors was right about what really causes depression? The short answer is, they were all right! The neurobiology of Major Depressive Disorder is complex and takes all these factors and much more into consideration. Our unconscious mind has a tremendous capacity to remember anything that we brush up against in our lives. It stores these memories in a code that allows it to compare previous interactions with the ones we are presently facing. It is always trying to read situations in an effort to maximize our pleasure while minimizing any risk for pain. Our mind is wired to do this constantly, using every sense we have at our disposal to serve us in 'the now'.

So what happens to our brain when we are under a scanner and when we are asked to make ourselves sad? First, we are asked to recount sad events to place our mind in this kind of state. We are then injected with a form of sugar that can be traced by the scanner. The sugar is taken up by the nerve cells in proportion to each cell's activity. Pet scans are then used to measure the amount of sugar that is present in each part of the brain as compared to normal. These scans are able to demonstrate the activity of the part of our brain that tags an emotion to a thought. When sad this part of our brain increases its activity (Area 25) while the thinking part of our brain (DLPC) decreases its activity. (See Neurobiology of Now)

The change of blood flow and metabolic activity in different brain regions is typical of how our brain responds to our needs each

 

 

 

 

A Brief History in the Diagnosis of Major Depressive Disorder

So let’s dive into this discussion and talk about what we have discovered so far about the “symptom cluster” we call Major Depressive Disorder. Back in the early 1970s when I first entered college, the etiology of depression was a ‘free for all’. Spiritual people said that it was a spiritual issue. Sociologists saw it as a social issue. Psychologists saw it as a psychological issue. And medical people… Well, you get the idea.

In the late 1980s and early 1990s functional scans of the brain became available. These allowed us to actually see the measurements of metabolic activity in various areas of a person’s brain real time. In addition to fMRI we now use morphometric MRI to measure the size of various brain regions. We use magnetic spectroscopy to measure the amount of a chemical in a specific brain region. We also have 'diffusion tensor imaging' to measure the density of axonal branching that connects one neuron to another.

What all of this has allowed is the development of various theories around why we see what we do. We have studied what happens in the brain when someone feels sad, anxious, angry, depressed, and what happens in these same areas when someone feels better or receives help of various types. One would think that this would allow us to have it all figured out! However, there remains many mysteries to what we are seeing. Even with all of this technology, individuals remain too variable in many aspects of brain size and activity to accurately diagnosis a person with depression.  Also, our brain is much more complex than anyone could have imagined. Down to the smallest ‘voxel’ we are able to measure there are at least 100,000 neurons providing at least 40 different functions. The brain works in widespread, complex, diffuse systems.

The Neurobiology of Major Depressive Disorder: What We Think We Know...for now!

So which one of my college professors was right about what really causes depression? The short answer is, they were all right! The neurobiology of Major Depressive Disorder is complex and takes all these factors and much more into consideration. Our unconscious mind has a tremendous capacity to remember anything that we brush up against in our lives. It stores these memories in a code that allows it to compare previous interactions with the ones we are presently facing. It is always trying to read situations in an effort to maximize our pleasure while minimizing risk for pain. It has been doing this for a long time. It is aware of things we will never be aware of. It is organized initially through our genetics. It is wired to do this constantly, using every sense and ability we have at our disposal to serve us in 'the now'. It is the seat of our Oneness.

So what happens to our brain when we are under a scanner and when we are asked to make ourselves feel sad? First, we are asked to recount sad events to place our mind in this kind of state. In a PET scan we are then injected with a form of sugar that can be traced by the scanner. The sugar is taken up by the nerve cells in proportion to each cell's activity. The scanner then measures the amount of sugar that is present in each part of the brain as compared to normal. These scans are able to demonstrate the activity of the part of our brain that tags an emotion to our thoughts. When we are sad this part of our brain increases its activity (Area 25) while the thinking part of our brain (DLPC) decreases its activity.

The change of blood flow and metabolic activity in different brain regions is typical of how our brain responds to our needs each moment of our life. Often one area of the brain activates as another reciprocally slows. This is much like other areas of the body, such as the interaction between the bicep and tricep muscles. As one contracts the other relaxes. In the brain when I need to think deeply, perhaps while giving a seminar, my ‘feeling circuits’ (ventral prefrontal cortical areas, VPFC) ‘get out of the way’ allowing my DLPC to respond to the task. However, should my wife enter the room this will likely reverse and the conversations will slow down a bit!

What about ‘being in the zone’? How do thinking and feeling circuits work then?  Basically, there are other systems to consider. One is the optimization of the conscious and unconscious mind. When the unconscious mind is allowed to lead, the conscious mind provides quiet oversight and various systems of the brain are optimized. This doesn’t mean they are perfect, however, they are as good as they can presently be. With practice, these circuits can improve moment-to-moment function considerably. Oneness training discussed in the engaged highest intent articles is about trying to live in this state.

So, what happens in the brain of a person with the ‘symptom cluster’ called ‘Major Depressive Disorder’? In some ways, it is similar to normal sadness. The emotional circuits are activated and, reciprocally, the cognitive areas of the frontal cortex are diminished. The difference is that the brain no longer is free to adjust back and forth according to the needs each situation presents. The cells distort life’s meaning with a predominance of negatively valenced interpretations of the river of sensations that flow by. The interpretive cognitive counterbalance is weak and without depth. These metabolic changes in the brain create an avalanche of cascading effects within the body. Highest mind is left with a distorted lens to respond to life’s messages. Our sense of self and our Higher Power feels distant or nonexistent. Spiritual people have told me, "I can no longer hear His voice." The straining emotional centers send their distorted messages to the midbrain, the command center for sleep, appetite and our immune system. Each emotional distortion interferes with the precious dance between mind and body. Our body struggles with a feeling of malaise and pain. It aches for a rest that never comes.

Over time the brain areas involved in memory storage may shrink under the strain. Our ability to process information slows. Our struggling immune cells may fall prey to inflammatory disease, cardiovascular disease and physical pain. This is the neurobiology of Major Depressive Disorder. So you can see, all of my professors were right. Depression includes all aspects of our life and we can help ourselves by addressing these many changes from each of these perspectives e.g. spiritual, social, cognitive, behavioral, dietary, medical among others!

Signs of Major Depressive Disorder
Major Depression: Everyone is Different
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