A man with virtually no serotonin or dopamine

Neuroskeptic covers a fascinating case of a man born with a genetic mutation meaning he had a severe lifelong deficiency of both serotonin and dopamine.

The case report concerns a gentleman with sepiapterin reductase deficiency, a genetic condition which prevents the production of the enzyme sepiapterin reductase which is essential in the synthesis of both dopamine and serotonin.

The most widely recognised symptoms of the condition, linked to the deficiency in dopamine which has an important role in controlling movement, are problems coordinating both conscious movements and the unconscious control of muscles that allows simple actions. Unconscious control requires that the brain signals one muscle to contract while releasing the complementary muscle, and problems with this process cause spasticity.

The effects the condition on serotonin, often stereotyped as the ‘happy chemical’, are less well known, but in this case it was clear that the patient wasn’t depressed but did some other difficulties:

These included increased appetite – he ate constantly, and was moderately obese – mild cognitive impairment, and disrupted sleep:

“The patient reported sleep problems since childhood. He would sleep 1 or 2 times every day since childhood and was awake during more than 2 hours most nights since adolescence. At the time of the first interview, the night sleep was irregular with a sleep onset at 22:00 and offset between 02:00 and 03:00. He often needed 1 or 2 spontaneous, long (2- to 5-h) naps during the daytime.”

After doctors did a genetic test and diagnosed SRD, they treated him with 5HTP, a precursor to serotonin. The patient’s sleep cycle immediately normalized, his appetite was reduced and his concentration and cognitive function improved (although that may have been because he was less tired)…

Overall, though, the biggest finding here was a non-finding: this patient wasn’t depressed, despite having much reduced serotonin levels. This is further evidence that serotonin isn’t the “happy chemical” in any simple sense.

This is another piece of evidence against the common myth that depression is “caused by low serotonin” although Neuroskeptic speculates whether the link between disrupted sleep and depression may indicate an effect of serotonin dysfnction.

Link to Neuroskeptic on ‘Life Without Serotonin’.
Link to summary of scientific paper.


  1. Foxx
    Posted March 24, 2010 at 5:33 pm | Permalink

    If someone had no serotonin how would they react to new variant Creutzfeldt-Jakob disease? would they be violent?

  2. Wendi
    Posted May 6, 2011 at 2:25 am | Permalink

    However, serotonin is not exactly a “hapy brain chemcial”. It is actually a mood regulator. Dopamine however IS a “feel good” neurotransmitter.

    My theories on why he wasn’t depressed are…

    1. He was able to generate just enough dopamine to keep himself happy.

    2. Another feel good hormone is phenyethylamine, it could have been he was able to produce enough of this to keep himself happy.

    3. If serotonin IS an anti-depressant, he was able to make enough of it to mantain a happy disposition.

    4. He DID have just enough serotonin to keep him happy (in the case it is the anti-epressant neurotransmitter).

    5. There IS a type of depression that we do not fully see as ‘true depression’. There are actually various types of depression, but not all of them have the classic stereotyped “oh, life is horribly unbarable…” sadness. This depression has sympoms like apethy, lethargy, chronic boredom, fatigue and thus, feeling the need to sleep a lot, (otherwise known has ‘the blahs’ by Julia Ross) which it sounds like he had. Thus, he could have very well been depressed, just not the sad, pitiful “woe is me” type we so often diagnose as depression.

  3. samer moukaddem
    Posted June 2, 2011 at 5:32 am | Permalink

    i used to take many medicine to raise my serotonine level in my brain
    i ve been 10 years in this way
    please please i need some help to get me out of this……………….
    thanks a lot if anyone could help…..

    • Mark Peterson
      Posted June 21, 2011 at 2:57 pm | Permalink

      Tried any medicine to raise your dopamine level instead?

  4. Posted January 25, 2012 at 12:31 am | Permalink

    These article shows how little do we know about serotonin, its receptors and precursors. But we still give these type of medicine to people and test it on them.

    Shame on US!

  5. Kenneth Casey
    Posted May 4, 2012 at 6:02 pm | Permalink

    Perhaps the absence of depression in the case of reduced serotonin and dopamine levels is because it is not so much the quantity of each neurotransmitter independent of each other, but the amount of each in comparison or in proportion to each other which affects a person’s feelings of well-being.

    This would be the case if these two neurotransmitters (NTs in the following text,) interacted with each other in a way in which the proper amount of dopamine was sufficient to positively impact a corresponding amount of serotonin. The decreased levels of both would result in less than ideal conditions, but these effects would be ameliorated in their impact due to the following factor — the quantities of each, though diminished, remain in the same proportion to each other.

    On the other hand, under the set of conditions in which the quantity of one of these NTs is diminished while the other remains unchanged, (or normal,) the individual’s feelings of well-being are thrown out of balance, the direction corresponding to which of the NTs is diminished.

    This is just an UN-educated guess, which I hope may carry enough truth (just a hair north of “0,”) to be of some use in cogitating on the causes of this enigma.

  6. Jake
    Posted September 20, 2012 at 10:48 pm | Permalink

    With modern research on 5-httlpr, and considering the notion that anxiety and stress give way to depression as a secondary disease:

    1-it is likely he wasn’t depressed because he didn’t have hardly any serotonin–higher synaptic serotonin levels cause anxiety

    2-with low serotonin, there’s nothing to inhibit dopamine, which means what little he had was at least partially functional.

    Really, this guy was likely immune to depression and intense emotion of any kind

  7. denis
    Posted June 24, 2013 at 9:53 pm | Permalink

    Maybe, since he was born that way, the little bit of serotonin this guy’s brain was producing was considered normal level by it’s serotonin receptors, and thus there was no depression. As far as I heard, those receptors are adjusting themselves. It’s like when you’re artificially increasing your dopamine, you develop tolerance, which is your receptors adjusting this elevated level as being normal. And then when you stop, you go through withdrawals, but they stop too after a while, when receptors start thinking this is the new normal level.

  8. John D
    Posted July 25, 2013 at 8:43 pm | Permalink

    I am 48 and had schizophrenia diagnosed when 22. I am medicated with paliperidone monthly injection. I do not have depression as such, but am aware of anhedonia, volition (reduced motivation and apathy) side-effects/ symptoms. I wish the scientists could somehow invent a medication, which included a feel good effect.

  9. Karlo
    Posted September 5, 2013 at 12:40 am | Permalink

    John: the medicine you wish for already exists. It’s called medical marijuana.

    • Tim Williams
      Posted April 24, 2015 at 9:08 pm | Permalink

      Medical marijuana? To a schizophrenic?!

      Truly some of the most horrifically wrong and stupid advice I have ever heard.

      Wake up from your pipe dream and stop blissfully promoting an agenda to the detriment of both others and common sense.

    • Mark
      Posted December 5, 2015 at 7:12 am | Permalink

      Marijuana has been shown to exacerbate depression in doses large enough to achieve a high, it only alleviates it in doses far smaller than a recreational user would use and it exacerbates it (and psychosis) in schizophrenics regardless of dose.

  10. JAL
    Posted November 9, 2013 at 3:49 pm | Permalink

    John D: That seems like low dopamine symptoms to me. Try a dopamine agonist yet? Works for me :)

  11. abby
    Posted November 18, 2013 at 8:55 pm | Permalink

    i was tested and found to have no dopamine and very little serotonin. i have had serious depression since i can remember. i’ve tried most everything. if i have to live like this the rest of my life i’d rather not live.

  12. Peter
    Posted October 18, 2014 at 8:53 pm | Permalink

    Serotonin only explains half the story. I really don’t think depression is solely attributed to serotonin dysregulation. It could be an interaction among several NTs at work and other factors in the body.

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