Depression is a common and serious mental health condition. The popular term ‘depression’ usually refers to “Major depressive disorder” as it is called in psychiatric literature. Depression is characterized by symptoms affecting the thoughts, feelings, and behaviors of a person. In depression, people lose interest in the activities they once enjoyed and demonstrate a general lack of enjoyment in life’s activities. It can also impact a person’s ability to function typically in their personal as well as professional life negatively.
Depressed Person
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How common is Major depressive disorder in the US?
Around 7.1% of the total US population aged 18 years or older is diagnosed with major depressive disorder in any given year. It is estimated 5% of the global adult population is suffering from Major depressive disorder. Most people with depression never seek help due to social barriers like stigma and lack of access to treatment facilities.
What causes depression?
The understanding of the causes and underlying pathophysiological mechanisms involved in depression has evolved. With time, some hypotheses have not survived critical scrutiny and scientific inquiry while other theoretical bases have provided a more in-depth understanding of the processes involved in depression. Some of the major understandings of the frameworks used to study the underlying pathology in depression are mentioned below.
The chemical imbalance theory
The idea first emerged in the 1950s when two drugs were observed to have a positive effect on mood. These drugs were not developed for depression at the time. One of them, Iproniazid, was used to treat tuberculosis and the other one, imipramine, was used as an anti-histamine drug. The observed effect of improving the mood was a side effect. Both of those drugs increased the quantity of serotonin in the brain so it was hypothesized that depression must be caused due to low levels of serotonin. This hypothesis became the focus of the research and a lot of research focused on establishing the effectiveness of anti-depressant drugs based on this hypothesis. Many drugs were developed on this basis and they have been widely used by the endorsement of psychiatric organizations and leading psychiatrists.
Over time, this theory based on serotonin depletion has been closely assessed and many loopholes in the underlying theoretical framework have been found. Ranging from no clinically observed positive effect of these drugs and delayed effect despite immediate action on the receptor site to lack of observed depression in patients who are given drugs like reserpine (it depletes serotonin).
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In 2022, a comprehensive review of psychiatric literature was published by two researchers investigating the evidence for this theoretical basis. They concluded that there is no clear evidence for the chemical imbalance theory. Although the psychiatric community already understood this, the chemical imbalance theory is quite popular and it is widely believed among the public. This review provides a thorough answer to this issue and puts the lid on an already diminishing conceptualization. However, anti-depressants tend to work in depression and it is currently not clear how anti-depressants produce their effect.
How are genes involved in causing depression?
Another area that has been the focus of scientific studies is genetics. Many studies have been conducted investigating the role of genes in causing depression and attempting to find the genes involved in this process. So far, it has been understood that genes do play a role in depression by making a person vulnerable to developing depression in life. It is currently estimated that the genetic basis of depression is complex and involves the inheritance and interaction of multiple genes. Scientists estimate that a person does not inherit depression from his parents but inherits a unique combination of genes that can increase/decrease the risk of depression. If one has a parent with depression, he/she is two to three times more likely to develop depression in life as compared to the typical person. So, the genes do increase the risk of depression but they are not the only factors playing a role in this.
The increased genetic susceptibility coupled with other environmental factors presents a more convincing explanation. Stressful events in life, other medical conditions, and other mental health conditions can trigger the onset of depression. It should be noted that the role of genetics, although observed in many studies, is an area of further study. The specific genes involved in the pathogenesis of depression, the specific gene combinations for depression, and their pattern of inheritance is further being studied. So, a lot is still to be known.
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Are there structural changes in the brain during depression?
Scientists also have focused their lens on understanding the biology of depression. The aim is to understand the changes in different regions of the brain in people with depression, how different regions communicate in depression, and how these changes and patterns of communication can enhance the understanding of the pathophysiology of depression.
In people with depression, many areas of the brain exhibit structural changes that can be observed with the latest imaging modalities like MRI (magnetic resonance imaging), and PET (Positron emission tomography). In people with clinical depression, increased activity and growth in size are seen in the amygdala region of the brain. Amygdala is associated with emotions. On the other hand, shrinkage and decrease in size have been observed in the hippocampus (involved in the processing of long-term memory) and the basal ganglia (Involved in thinking, memorizing, and emotional regulation) regions of the brain. The ‘brain changes’ framework is an interesting area as it can provide useful information about different circuits and regions of the brain involved in depression. And it can also provide useful insights into the mechanism of action of anti-depressant drugs.
Role of child abuse/neglect
Many studies have been conducted studying the link between various forms of child abuse and the increased risk of depression later in life. Child abuse is understood to increase the risk of developing depression and other mood disorders. Childhood neglect or abuse produces many structural changes in the brain and it also produces widespread inflammatory changes making the person vulnerable to the onset of depression. Furthermore, childhood neglect can trigger depression in a child already susceptible to depression due to increased genetic
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Final thoughts
Overall, there are many areas of research for understanding the causes and pathogenesis of depression. And although one cause or mechanism is not definitive, they still provide useful insights about the processes involved in depression. The understanding of these processes has gone through an evolutionary process over time and further research is being conducted in many areas to enhance this understanding.
References
https://www.technologynetworks.com/neuroscience/articles/a-popular-theory-of-depression-wasnt-debunked-by-a-new-review-it-got-debunked-years-ago-363986 (Accessed on March 12, 2023)
https://www.health.harvard.edu/mind-and-mood/what-causes-depression (Accessed on March 12, 2023)
https://med.stanford.edu/depressiongenetics/mddandgenes.html (Accessed on March 12, 2023)
https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2019.19010020 (Accessed on March 12, 2023)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405681/ (Accessed on March 12, 2023)
https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2020.20060845 (Accessed on March 12, 2023)
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