What Is the Connection between the Hippocampus and Depression?

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  • Written By: T. Broderick
  • Edited By: Heather Bailey
  • Last Modified Date: 17 August 2019
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The connection between the hippocampus and depression is that the constant release of glucocorticoids due to stress causes depression by affecting the hippocampus. The hippocampus has a large number of glucocorticoid receptors, and will atrophy if overexposed. A malfunctioning hippocampus leads to severe, even clinical, depression. A medical condition known as Cushing's syndrome is also possible. Using antidepressants is the preferred method of treating these forms of depression.

The hippocampus plays a major role in the conversion of short-term memory to long-term memory. Humans' short-term memory occurs in the prefrontal cortex. The hippocampus examines these new experiences for those needing long-term storage, such as an important event or new skill. As one's emotional state greatly influences whether or not a short-term memory will become a long-term one, certain hormones inform the hippocampus of one's emotional state. Glucocorticoids are a class of hormones that directly tie together the hippocampus and depression.

Glucocorticoids are steroid hormones; every cell in the human body has receptors for them. These hormones help regulate glucose levels, and as a medication they reduce bodily inflammation. In the hippocampus, their job is to solidify flashbulb memories into long-term memory; flashbulb memories are the immediate details surrounding oneself when emotionally arousing news is heard. Yet if one is under constant stress from work or other circumstances, the release of glucocorticoids from the adrenal cortex is higher than usual. The effects on the hippocampus are physically and psychologically detrimental.


Though constant stress does not have the same effect that occurs with flashbulb memories, the brain becomes accustomed to retaining only stressful memories, creating depression. This, in turn, creates more stress and depression. The hippocampus and depression also have physical consequences. The hippocampus physically shrinks in response to constant glucocorticoids. Reduced size causes atrophy and can lead to a number of more serious psychological conditions.

Clinical depression can result from this degenerative cycle. One experiences a constant low mood and loses interest in things that previously gave pleasure. The condition has physical side effects such as insomnia and rapid weight gain or loss. Clinical depression can also manifest as unexplained physical pain.

Another condition that can arise due to the negative connection between the hippocampus and depression is Cushing's syndrome. Raised levels of cortisol and glucocorticoids cause it to develop. Though other underlying conditions such as cancer can raise cortisol levels, severe depression has the same effect. A patient with Cushing's experiences rapid weight gain in the torso, impaired sexual function and multiple skin disorders. Physicians generally test for cancer and other life-threatening conditions before depression is considered as a root cause.

No matter if the connection between the hippocampus and depression causes mild depression, clinical depression or Cushing's syndrome, the most clinically reliable treatment is using antidepressant medication. Certain types of these medications can block the absorption of glucocorticoids by the hippocampus so that it has a chance to resume normal function. For most patients, medication is paired with therapy sessions that can discover and address underlying stress.


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