What is the underlying pathophysiology of major depressive disorder (clinical depression)?

Updated: Aug 06, 2020
  • Author: Jerry L Halverson, MD; Chief Editor: David Bienenfeld, MD  more...
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The underlying pathophysiology of major depressive disorder has not been clearly defined. Current evidence points to a complex interaction between neurotransmitter availability and receptor regulation and sensitivity underlying the affective symptoms.

Clinical and preclinical trials suggest a disturbance in central nervous system serotonin (5-HT) activity as an important factor. Other neurotransmitters implicated include norepinephrine (NE), dopamine (DA), glutamate, and brain-derived neurotrophic factor (BDNF). [9] However, drugs that produce only an acute rise in neurotransmitter availability, such as cocaine or amphetamines, do not have the efficacy over time that antidepressants do.

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