Moods by nature fluctuate, and everyone experiences highs and lows in their lives, but in some cases, changes in mood can become destructive for a prolonged period and can impair a person's ability to keep a job, or maintain meaningful relationships. It is estimated that about ten percent of people will suffer from depression. At some point in their lives, mood disturbances are usually characterized by various symptoms, including feelings of distress, sadness, not full of excitement, excessive tiredness, and loss of interest in once-pleasant activities, such as anhedonia. Many people with depression also suffer from anxiety. Neuroimaging studies have revealed that many of the brain circuits that normally regulate Moods are erratic in depression The amygdala is located deep in the brain processes very prominently stimuli such as: Rewards and potential threats In depression the amygdala is overactive and overly responsive to negative events In turn, the amygdala works to connect a group of brain regions that expands the functional and behavioral response to emotional stimuli These areas include: the medial prefrontal cortex and the nucleus.
Nucleus accumbens, hippopotamus, and insula Depressed individuals are most susceptible to stress, which can cause changes in brain structure, including hippocampal atrophy. Other changes caused by depression may cause inappropriate reactions to emotional events. The medial prefrontal cortex is involved in regulating how strongly we respond to emotional stimuli. Antidepressants, cognitive behavioral therapy , and electroconvulsive therapy are all treatments that affect the structure and function of these and other brain regions . Animal models such as mice are critical in helping us understand cellular and molecular changes. Underlying Depression and Developing Better Treatments The stress pathway These models may still shed light on the biology of depression and are as close as possible As in humans: Chronic stress in mice can lead to atrophy of the hippocampus and prefrontal cortex Neurological studies in mice have also shown that it alters neuroplasticity in different brain regions including the hippocampus , temporal cortex, amygdala The brain and nucleus accumbens in the normal hippocampus experiences can lead to changes in the connections between neurons that lead to learning These changes are referred to as flexibility as chronic stress can reduce this flexibility Healthy brains also continue to produce new neurons in one molecule From the hippocampus these new neurons mature slowly and integrate into neural circuits where they have a strong influence on hippocampal activity and behavior.
These new neurons are also affected by stress. Their number decreases in a stressed brain. These effects may result from decreased levels of BDNF , which consists of neurotrophins that increase neurodevelopment and flexibility. Reduced flexibility may stop the hippocampus from being able to properly regulate the stress response, which can lead to a vicious cycle where stress leads To more stress the hippocampus is particularly affected, but there can be reduced flexibility elsewhere in the brain and together these changes could contribute to other symptoms of depression such as anhedonia. The cellular changes seen in mice that are involved in human depression remain unclear. Most antidepressants available today rapidly increase the amount of the neurotransmitters serotonin and norepinephrine in synapses.
However, improvement in symptoms in patients and mice usually does not occur until weeks after starting treatment. While the reasons for this delay are not fully understood , prolonged treatment with antidepressants Depression can, over time, reverse some of the changes caused by chronic stress, increase neurotrophic factor , and restart hippocampal flexibility. Non-Chemical Treatments Antidepressant drugs including ECT also enhance flexibility in the hippocampus in rats Antidepressant therapy can also reverse stress-induced change in other areas of the brain including the prefrontal cortex and reward system neural circuits Different treatments may target different regions to improve symptoms in a timely manner Finally, ketamine was found to have rapid antidepressant effects in depressed patients with prolonged effects for days. The mechanism behind this is an active area of research. Ketamine works to block a type of synaptic transmission, which leads to activation of a number of signaling pathways and an increase in neurotrophic factor.