Wednesday, April 10, 2013

Do Low Levels of Serotonin Cause Depression?

The conventional wisdom is that depression is caused by low levels of serotonin, the neurotransmitter in your brain that is responsible for memory, sleep, appetite, learning, and the regulation of your feelings including happiness and welling being. Therefore, if you have a chemical imbalance in the brain antidepressants, like Prozac or Zoloft, can alter your brain chemistry and fix the imbalance, as well as, enhance the profits of the big pharmaceutical companies. Strange then that scientific research cannot find any reliable flaws in the serotonin system of the depressed. (1) You see, even if antidepressant medications do increase serotonin levels in the brain and help some feel better, this doesn't mean that low levels of serotonin cause depression. Aspirin can cure a headache but that doesn't mean that low levels of aspirin in the brain cause your head to hurt.

The brain cells that deal in serotonin (called serotonergic neurons) have "arms" that reach out to all areas of the brain. The extensive connections and super pathways of serotonergic neurons comprise the single largest system in the brain. To transmit a message the sending neuron releases the chemical serotonin to be absorbed by the receiving neuron. However, more serotonin is released than is needed so the excess is either "vacuumed" back up into the sending neuron or metabolized by an enzyme and removed as waste. The enzyme metabolizes serotonin into 5-Hydroxyindole acetic acid or 5-HIAA. Researchers can look at spinal fluid for 5-HIAA and gauge the level of serotonin in the brain. So if low-levels of serotonin cause depression, then all people suffering from depression will have low-levels of 5-HIAA in their spinal fluid. (2) Seems simple enough.

But there are two studies I'd like to bring to your attention that seem to debunk the chemical imbalance theory of depression. In one, researchers in Stockholm looked at the 5-HIAA levels in the spinal fluid of 68 depressed patients as assessed in nanograms per milliliter. 29% had low level counts below 15 nanograms, which would seem logical in depressed patients, but 47% had regular counts between 15 and 25 nanograms, and 24% of the depressed patients had HIGH LEVELS above 25 nanograms. What is interesting is that the control group of volunteers who were NOT depressed had almost the same exact bell curve of 5-HIAA levels. 25% of the control group had low counts below 15 nanograms, 50% had counts between 15 and 25 nanograms, and 25% of the non-depressed patients had high levels above 25 nanograms. (3)

To summarize this amazing research: 29% of the depressed patients had low levels of serotonin but so did 25% of the non-depressed "normal" control group patients. Plus 25% of the depressed patients had high-levels of serotonin. All in all, the median level of 5-HIAA in the spinal fluid of the non-depressed "normal" group was 20 nanograms but the research showed that 37 of the 68 depressed patients, more than half, had levels ABOVE that "normal, non-depressed" average. Kinda blows a hole into the low-serotonin causes depression theory. Oh, and this study was done in 1974, 14 years before Prozac, the first in a line of antidepressants that flood your brain with serotonin to "cure" depression.

The National Institute of Mental Health (NIMH) in 1984, four years before Prozac, conducted the other study I wanted to mention. They were investigating the efficacy rates of a proposed antidepressant drug named Amitriptyline that, like Prozac, prevented neurons from vacuuming back up the excess serotonin, thus flooding the brain with extra serotonin. They also looked at depressed patients 5-HIAA levels and, surprise, surprise, found a wide variety, from low to high. The NIMH scientists concluded that, "Elevations or decrements in the functioning of serotonergic systems per se are not likely to be associated with depression." (4) To say that in plain talk, there is no evidence that there is anything wrong with the serotonin brain system of depressed patients. There seems to be a huge disconnect between those pretty antidepressant commercials and the actual scientific research. (5)

Low Serotonin Level Problem 1- If low levels serotonin was a major player in causing depression, then increasing serotonin should alleviate depression right away. Antidepressants raise serotonin levels within hours but it can take weeks for a depressed person to show signs of improvement. Also, after a few months, some people relapse into depression, even while still on antidepressants.

Low Serotonin Level Problem 2- If low levels of serotonin cause depression, then all people with low levels of serotonin should be depressed, but this is not the case. Also, there are people who suffer from depression who have regular levels of serotonin in their brain and depressed people with high levels of serotonin.

Low Serotonin Level Problem 3- There are drugs that don't work on the serotonin system in the brain yet also appear to relieve the symptoms of depression. Welbutrin is a very popular antidepressant but works on the neurotransmitters dopamine and norepinephrine.

Studies indicate that serotonin seems to somehow play a role in depression but the question remains, do the lower levels of serotonin cause depression, or does a particular person's depression create those lower levels of serotonin?


1. Moncrieff, J., (2009). The Myth of the Chemical Cure: A Critique of Psychiatric Drug Treatment. Palgrave Macmillan; Revised edition, 2009.

2. Whitaker, R. (2010). Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs and the Astonishing Rise of Mental Illness in America. Crown Publishing.

3. Asbert, M. (1976). Serotonin depression: A biochemical subgroup with the affective disorders? Science,191, 478-80; Asberg, M., (1976). 5-HIAA in the cerebrospinal fluid. Archives of General Psychiatry33, 1193-97.

4. Maas, J. (1984). Pretreatment neurotransmitter metabolite levels and response to tricyclic antidepressant drugs. American Journal of Psychiatry141, 1159-71.

5. Lacasse, J., Leo, J. (2005) Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature. PLoS Med2(12): e392. doi:10.1371/journal.pmed.0020392

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