The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 4 • August 2015


by Sandy Shaw

Here is a remarkable paper published in 2012 (Robinson, 2012) that shows that SEROTONIN IS CRITICAL FOR PUNISHMENT-INDUCED INHIBITION. This could relate to a great many situations where paying attention to punishment is an important social signal telling a person what they shouldn’t be doing. (Of course, there are also many situations where social rules and regulations that include punishments if you don’t do them are things where you have good reason for not wanting to do them, but lets start with the experiment to keep things simple.)

The results of the study are very interesting but it included only female subjects. (I think this would have been a more interesting paper with men as the subjects, since it seems pretty obvious that the male gender is less sensitive to punishment-induced inhibition, if you can judge by (say) the number of fights your male siblings get into as compared to their sisters or the overwhelming number of men in prison for violent crimes as compared to women imprisoned for the same.) In any event, there were 41 healthy young female subjects (mean age 27.6). The key part of the experimental treatment was that 21 of the women were given a “balanced amino acid mixture” that contained tryptophan, the precursor to serotonin, while the other 20 women consumed the same amino acid mixture but without tryptophan. Thus, the latter 20 women received a tryptophan-depleting amino acid mixture to consume.

The researchers collected data on the subjects via questionnaires to account for various aspects of personality, such as impulsiveness, venturesomeness, and empathy to control for possible confounders. The very interesting overall result was that serotonin promotes the inhibition of responses to punishing outcomes, at least in females but almost certainly in males. What this means is that when people are in a state of serotonin depletion (induced in the experiment by a tryptophan depleting amino acid drink) they may be less likely to respond to punishment by being inhibited by it. This could obviously lead to resistance to social mechanisms of punishment. Depending on the situation, this could be good (resisting punishment by Hitler’s goons for assisting Jews) or bad (not paying attention when punished for stealing somebody’s bicycle).

We could even think of reducing recidivism by putting parolees on a high tryptophan diet (such as one enriched in whey protein) to keep them sensitive to social punishment for committing crimes. (Here, Durk wanted to emphasize the importance of being able to convert tryptophan to serotonin, which requires the enzymatic conversion of tryptophan to 5-hydroxytryptophan, 5-HTP. See Durk’s comments below for more on this.)

This paper included only female subjects, but other aspects of serotonin psychopharmacology work the same in males in published scientific studies, such as regulation of impulsiveness. The amazing idea conveyed by this paper is that the consumption of tryptophan is a major element in the social fabric with fascinating implications as to social control. Orwell might have been amazed.

A couple of speculations: Libertarians may be people who have a reduced sensitivity to social punishment, considering their resistance to being told what to do by “authorities.” If true, it could be due to a deficiency of dietary tryptophan or, I think rather more likely, a genetic or epigenetic disposition to be less sensitive to these signals (such as a reduced ability to convert tryptophan to 5-HTP on the pathway to making serotonin). Another speculation would be that children who don’t respond to punishment might be more likely to do so if fed a diet enriched in tryptophan, as is found in whey protein for example (Whey protein has been found to be an antidepressant in a study involving mice) (Ahmed, 2011). Bananas are also highly enriched in tryptophan. A 5-HTP-containing supplement could be an option for those who do not respond to increased dietary tryptophan. You have to keep in mind, though, that if your demands are not perceived as reasonable, your kids may not respond to punishment anyway.

The two of us also speculate that children born in and raised during a war, where their fathers are frequently absent, may also be less sensitive to punishment-induced behavioral inhibition due to the possibility that punishment coming from a father (the stronger, more aggressive, probably larger parent) may be more effective than that from a mother. Just a speculation that we have not seen tested. We would be very interested in research looking for epigenetic effects of being born and raised in wartime. One to look for might be methylation of the promoter for the tryptophan-5’-hydroxylase gene.

Finally, I think this paper might have received more attention than it did if the authors had given it a title that made it a little more clear what they had shown in the experiment. For example, the title “Serotonin is Critical for Punishment-Induced Inhibition” says it with a little more pizazz and understandability and emphasizes its importance. Read the original paper title just below to see what I mean.


  • Robinson, Cools, Sahakian. Tryptophan depletion disinhibits punishment but not reward prediction: implications for resilience. Psychopharmacology. 219:599-605 (2012).
  • Ahmed, Eldenshary, Nada, et al. Pharmacological study of the possible antidepressant activity of whey protein isolate in mice. Aust J Basic & Appl Sci. 5(12):2649-59 (2011).


by Sandy

with additions suggested to me by Durk Pearson

On converting tryptophan to serotonin: Some people have a reduced ability (due to a lower activity variant or a deficiency of the necessary enzyme) to convert tryptophan to 5-hydroxytryptophan (5-HTP), the first step in the conversion of tryptophan to serotonin. That is why some individuals who use a 5-HTP containing supplement find that it makes them feel better than if they just take a tryptophan supplement.

On dietary change: It is amazing but true that people are very resistant to changes in their diet to the extent of allowing themselves to starve if given food with which they are not familiar. It may be easier to get someone to take a tryptophan or 5-HTP containing supplement than it is to get them to include whey protein or bananas in their diet.

On SSRIs: Selective serotonin reuptake inhibitors, such as fluoxetine (Prozac®) have been associated with some rare but horrendous massacres by certain students (male but importantly taking an SSRI) at public schools. Most people who take SSRIs find that they feel better and are more able to cope with people they don’t like being with, such as where they work. However, for a certain minority of SSRI users, serotonin can be depleted. SSRIs work by increasing the length of time that serotonin occupies the synapses where its signal is generated, preventing that serotonin from being taken back up, while the serotonin is present in the synapse, into the vesicles where some of it will be destroyed by the enzyme monoamine oxidase or it could be stored for reuse. Hence, there are those who, when taking SSRIs can deplete their store of serotonin and end up behaving as do those with serotonin depletion, insensitive to inhibition by punishment as well as being more prone to impulsive violent actions, a deadly combination in rare cases such as Columbine. (Keep in mind that newspapers publicize all these deadly attacks but not all the immensely larger number of instances when no such deadly attacks took place, giving you an insanely biased idea of how often these school massacres take place and of how dangerous it is for kids to be using SSRIs. (NOTE: We have not studied the literature in detail for how often these adverse effects take place or what sorts of kids may be vulnerable to such adverse effects from SSRIs that can take place in some kids using SSRIs, so don’t take this as a recommendation for or against it. SSRI use is correlated with violent behavior, but correlation is not necessarily evidence of causation though it may be causative. Be particularly cautious in the use of SSRIs by individuals who have agitated depression, who may be particularly sensitive to impulsive acts of violence on SSRIs.

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