last updated 23-05-2024



The pathophysiology of depression is unknown. However, the modified biogenic amine theory is the most commonly accepted hypothesis. In this theory, chronic dysregulation of the neurotransmitter systems (5-HT, NE, and/or DA) occurs. As an example, the graphic focuses only on serotonergic activity, but this same situation probably occurs for other neurotransmitters.

Note that serotonergic activity can be altered by different mechanisms. First there can be a depletion in the 5-HT supply due to diet without tryptophan, a decrease in production of neurotransmitters or a decrease in the amount of 5-HT released per nerve impulse. Also an increased inhibition by pre-synaptic receptors can decrease neurotransmitter release. So, decreased amounts of 5-HT in the synaptic cleft lead to decreased activity of the postsynaptic receptors and thus decreased signal transmission leading to symptoms of depression.

The postsynaptic cells try to compensate this decreased activity by up-regulating postsynaptic 5-HT receptors.





The physiological result of the decreased receptor activities can be determined by examining the neuronal systems. Serotonin’s cell bodies are located in the midbrain Raphe, and it's neurons project to the:

  1. frontal cortex where they may have important regulatory functions for mood
  2. limbic areas where they may modulate emotions, particularly anxiety
  3. basal ganglia where they may regulate movements
  4. hypothalamus where they can regulate eating, appetite, weight, the sleep-wake cycle and sex drive

Norepinephrine’s cell bodies are located in the locus coeruleus, and it's neurons project to the:

  1. frontal cortex to regulate mood, cognition and attention
  2. limbic areas to regulate emotions and anxiety
  3. hypothalamus for regulation of eating, appetite, weight, sex drive, and pleasure
  4. cerebellum which may modulate motor movements

Also check the Kompas for more information on depression and its treatment. And check 5-HT neurons for better understanding of the events occurring in the serotonin neuron.


Which of the following mechanisms help to clear the synapse of neurotransmitter after neurotransmission? 


Dysregulation of the 5HT and NE neuronal projections to the frontal cortex can lead to all the following symptoms of depression except: 


Depressive symptoms can only be present when a patient has a decrease in synaptic neurotransmitter concentrations. 


Depression results from a change in receptor density at both the post-synaptic neuron and the neuronal body. 


Depression can occur from a dysregulation of dopamine, norepinephrine, and serotonin or all of these.