Biological basis of depression

- In this video I'm going to talk about the biological basis of depression. Depression. And I'm not talking about just a passing bad mood but I'm talking about major depressive disorder. Major depressive disorder is a major cause of distress, disability and death from suicide. It is the prototype of the category of mental illnesses called the depressive disorders which involve distress or disability from abnormally negative mood. In addition to negative mood the depressive disorders often involve related symptoms such as feelings of hopelessness or loss of enjoyment in activities. As of 2014 when I'm making this video our understanding of the cause of major depressive disorder is still very limited. When we look at the brains of patients that have major depressive disorder either with the naked eye or with traditional microscope studies there are basically no consistent abnormalities that have been seen in the tissues of these patients. However special scans and research involving animal models have suggested that there are some functional abnormalities that can be detected in the brains of many patients with major depressive disorder. So here in this illustration of the brain we're looking at the outside of the brain and the different lobes of the cerebrum, the top part of the brain, have been labeled with different colors. And in this illustration we're also looking at the brain but it's been divided into right and left halves and we're looking at the inside of, in this case, the left half of the brain. And a couple of specific areas that have seemed to have abnormal activity in these studies involve this part of the brain in this light blue color which is called the frontal lobe. Let me just write that. Frontal Lobe. A lobe that's most towards the front of the brain. And over here on the inside that would be all of this stuff, all of this stuff right here is also the frontal lobe. And the other part can't be seen on the outside it can only be seen on this inside view involves a number of different structures like this structure here and some others that are behind the brain stem over here that are called the limbic structures. Let me just write that word down. The limbic structures. Limbic structures, right here. And these studies have suggested that there appears to be abnormally decreased activity in areas of the frontal lobe and areas of increased activity in areas of the limbic structures. These findings seem to fit well with other studies showing a role for these parts of the brain in regulation of the emotions and in particular, responses to stress. Functions of the brain that seem to be particularly abnormal in patients with major depressive disorder. In regards to stress it's also been noted that many patients with major depressive disorder have abnormal blood concentrations of certain hormones that are particularly associated with stress. For example the hormone cortisol that's a major stress hormone. There's a particular area of the brain that controls most hormones including the stress hormones that's located right here. And this area is called the hypothalamus. Hypothalamus. And the hypothalamus talks back and forth to many areas of the brain but two areas in particular that it communicates with back and forth are the frontal lobe and the limbic structures of the brain. So it's thought that perhaps abnormal communication between the frontal lobe and the limbic structure and the hypothalamus in major depressive disorder play a role in why there are these abnormal concentrations of certain hormones related to stress in the blood stream of these patients. These stress hormones may affect most tissues of the body but they also effect the brain itself including the frontal lobes, the limbic structures, and the hypothalamus that actually controls their amounts in the blood in the first place. So for major depressive disorder it's still unclear which abnormalities of these stress hormones are causes and which are effects of the disease itself. Some features of major depressive disorder also appear to involve abnormalities in neuronal pathways using certain neurotransmitters, the molecules that communicate between neurons in the brain, and the abnormalities of these pathways may cause abnormally decreased or increased activity in certain parts of the brain like the frontal lobes and the limbic structures. Collections of many of these neurons that produce these neurotransmitters have their somas, or their cell bodies, in a few areas of the brain stem, this structure below the cerebrum, and then their axons project to many areas up in the cerebrum, including the frontal lobes and the limbic structures. One of these pathways start in what are called the raphe nuclei of the brain stem. And there are several groups of raphe nuclei at different levels of the brain stem that send projections up to many areas of the cerebrum including the limbic structures and the frontal lobe, and they're responsible for much of the serotonin that's secreted in the brain. Serotonin. Which appears to be abnormal in many patients with major depressive disorder. Another pathway starts in an area called the locus coeruleus. Which is located right around here in the brain stem and it also sends long axons up to different areas of the cerebrum and releases a lot of the neurotransmitter called norepinephrine. Norepinephrine. And this also appears to be abnormal in many patients with major depressive disorder. Then there's a pathway that starts with an area called the ventral tegmental area. Which I'll just write as VTA for short, which is located around here in the brain stem and which also sends long axons up to different areas of the cerebrum. And the ventral tegmental area supplies much of the dopamine to the brain. Dopamine. These neurotransmitter systems affect the function in many parts of the brain including the frontal lobes and the limbic structures and supporting the idea that abnormalities of these systems are involved in major depressive disorder is the fact that medications that affect these different neurotransmitters dopamine, norepinephrine, and serotonin often improve the symptoms of major depressive disorder. A newer idea that is interesting is that there may be abnormalities of what is called neuroplasticity. Neuroplasticity. Which is a big word that just means that the brain changes in response to experience and these changes may occur down at the level of connection between a couple of brain cells, a couple of neurons in the brain where the strength or efficiency of information flow from one neuron to the next may change based on experience. Or it may happen that the level of networks of neurons that are widespread, different kinds of connections and pathways that informations flowing through the brain based on the experience that the brain is having. And evidence is accumulating that aspects of neuroplasticity appear to be abnormal in animal models of major depressive disorder. But like the other abnormalities that have been found so far it's unclear if these abnormalities of neuroplasticity are a cause or an effect of major depressive disorder. So there have been a number of biological abnormalities found to go along with the mental abnormalities we see in major depressive disorder. Biological. And other clues to biological factors that may be involves in the cause of major depressive disorder include genetic studies that suggest that a predisposition can be inherited. Several genes related to brain function have been associated with the risk of developing the disease. It may be that these genetic abnormalities increase the risk of the brain developing abnormal responses to negative or stressful events particularly early in life when the brain is still rapidly developing in response to experience but like most if not all mental disorders in addition to the biological factors there does appear to be psychosocial factors as well. Psychosocial factors. Certain psychosocial factors have been linked to the risk of developing major depressive disorder such as childhood abuse, stressful events, or limited social support during adverse circumstances, so that it may be for many, if not most people with major depressive disorders as with most other types of mental illness it seems that an unfortunate constellation of both biological and psychosocial factors combine to cause the illness.