A Review of the Biochemistry of Depression


These are Neurons:

Well, they don’t really look like that, but this drawing is used for educational purposes.

Neurons “communicate” by releasing neurotransmitters from the pre-synaptic neuron (on the left in this drawing) which drift by Brownian motion through the synaptic cleft to the post-synaptic neuron (on the right in this drawing).

When  a person finds themselves in the position of being subjected to chronic stress the individual will “fire off” their neurons at a rapid rate in an attempt to “solve” the problem or escape from the stress.  If the stressors are external the person may be able to restructure their life to decrease the chronic stress.   It is characteristic of emotional conflicts that the person repeatedly finds themselves in a position of stress, despite their best intents.  In the situation where the individual can not escape chronic stress the body becomes depleted in one of the neurotransmitters.


This is a normal neuron firing 



This is a depleted (that is, depressed) neuron firing 



A depletion of one of the neurotransmitters results in the symptoms of depression:

      • Feeling tired most of the time, even with adequate rest
      • Disturbances in sleeping habits
      • Irritability, leading to upsets over little things that might not ordinarily be bothersome
      • Sadness, sometimes breaking into tears
      • Loss of sex drive, often complete
      • Headache, which is usually not severe but which seems to be present much of the time as a dull ache or a band around the head and tending to radiate down the neck
      • Chronic pain in the back, abdomen, or almost anywhere else, which may be quite severe and is real, not imaginary
      • Lack of enthusiasm or feelings of enjoyment, even for doing those things that were formerly favorites
      • Difficulty concentrating, making decisions, studying, or getting things done
      • Indigestion, constipation or diarrhea, changes in appetite that often lead to weight loss or, in a few cases, to overeating and weight gain
      • Feeling unwanted, sinful, guilty or worthless, sometimes leading to the thought that life is not worth living

Having some of these symptoms is normal.

Having 6 or more is an indication of probable depression and a more formal evaluation is indicated.



Antidepressants work by decreasing the reuptake and distraction of the neurotransmitter by the pre-synaptic neuron.  With more of the neurotransmitter left in the synaptic cleft the likelihood of   “normal” neural transmission is enhanced and the symptoms of depression are ameliorated.  However, unless the person escapes the chronic stress by the change in external circumstances or by psychotherapy, the person remains vulnerable to the symptoms of depression.  Antidepressants are a treatment and not a cure.


Psychotherapy works by allowing the individual to explore the issues that led the chronic stress.  This work is done in the context of a supportive therapeutic relationship that permits the individual to take the emotional chances necessary to review and recast earlier events and relationships.

Biochemical Testing

At Michigan Psychotherapy  we evaluate the biochemical status of depressed individuals using a 24 hour urine for 3,4-MHPG.  3,4- MHPG is a CNS-only metabolite of norepinephrine, one of the neurotransmitters.  Unfortunately there is not a CNS-only metabolite of serotonin, the other major neurotransmitter responsible for the maintenance of mood.  CNS serotonin metabolites are swamped by the metabolic products from the rest of the body.

If the MHPG is reported to be low we have direct evidence that there is a deficit in the CNS metabolism of norepinephrine.  If  the MHPG is reported as being high, by the balance theory, we presume that the serotonin metabolism is depleted.  In the third case, where the MHPG is reported as being in the normal range, the test is of no direct help.  However, because the test is only ordered for  individuals who are clinically depressed, we infer that because the norepinephrine metabolism is not depleted, the serotonin metabolism must be.

For a patient showing the signs of depletion of norepinephrine, we use a norepinephrine reuptake blocker.
For  depletion of serotonin we use a SSRI (selective serotonin reuptake inhibitor).