The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 19 No. 6 • July 2016


PERSONALITY AND THE COMT GENE

Personality generally “refers to the ‘characteristic patterns of behavior, thoughts and feelings’ of a person over time.” (Montag, 2015)

One cannot really understand human personalities without knowledge of dopamine and COMT (catechol-O-methyltransferase), the latter being one of the enzymes that catabolizes and inactivates dopamine. Dopamine is a neurotransmitter importantly involved in the brain’s reward circuitry. Its regulation is responsible for much of the personality differences exhibited by individuals. People who have certain variants of specific dopamine receptors show very different patterns of behavior. The DRD2 and DRD4 dopamine receptor genes are associated with, for instance, impulsivity, novelty-seeking, and risk-seeking (tending to engage in more risky types of behavior) and linked to lower levels of dopamine release.

The COMT Val158Met polymorphism (version) of the COMT gene is a high activity version of COMT, that is, it breaks down more dopamine than the Met/Met COMT polymorphism. “Carriers of the Met/Met variant [of COMT] catabolize three to four times less dopamine than carriers of the homozygous Val/Val variant.” (Montag, 2015) By catabolizing less dopamine, this means that there is more dopamine available to activate dopamine receptors. COMT Val158Met, on the other hand, causes there to be LESS dopamine available to activate dopamine receptors.

Met stands for methionine, Val for valine; the gene can either specify a valine (Val) or a methionine (Met) at position 158 and this importantly defines how strongly the COMT enzyme degrades dopamine. The variant most commonly found has a Met and a Val at that position and is called the Val158Met polymorphism. That variant is associated with a very interesting personality type that in its most productive form is found in people such as entrepreneurs, inventors, and similar types who also share personality characteristics such as being risk takers and novelty seekers. At the extreme end of the spectrum of those who have this variant may be found people who have a tendency to engage in impulsively reckless activity or thrill-seeking, and may even, in some cases, use addictive drugs.

The authors of Montag, 2015 explained that they searched the PubMed.gov literature for papers on COMT Val158Met and found that, at the time, there were nearly 400 papers on the subject. They then narrowed the search by using the keywords “COMT Val158Met” and “personality” as search terms and received back 56 papers. (They also searched “Google Scholar” using these keywords.) Ultimately, they focused on papers dealing with “COMT in the context of [ ] [certain] biologically oriented personality theories...” The literature on COMT continues to rapidly increase.

INHIBITING COMT TO DECREASE DOPAMINE

DEGRADATION IN THE BRAIN

GREATER REWARDS™

We developed a formulation called GREATER REWARDS that we take regularly to inhibit COMT to reduce the degradation of dopamine, thereby increasing the reward signaling of dopamine. One of its ingredients is EGCG, epigallocatechin-3-O-gallate, the major catechin found in green or white tea. EGCG is a high-potency inhibitor of COMT (catechol-O-methyltransferase). (Zhu, 2008)

Another ingredient in our GREATER REWARDS is taurine. Taurine increases dopamine levels in the dopamine reward system. The rat dopamine reward system is organized like that of humans, with the mesolimbic dopamine neurons projecting from the ventral tegmental area to the nucleus accumbens. Researchers looking for receptors involved in the regulation of dopamine in this pathway reported that local perfusion of taurine (by microdialysis) increased dopamine levels in the nucleus accumbens reward center and that this involved taurine acting as an agonist at (activating) glycine receptors. (Ericson, 2006)

Another constituent of GREATER REWARDS is quercetin, a flavonoid found in many plants. It has been shown to possibly inhibit COMT. (Singh, 2003; Nagai, 2004)

We’ve also added lithium. In the low concentrations found in drinking water and in some mineral waters, lithium has a protective effect against suicide and reduces the number of arrests for robbery, burglary, and theft, suggesting that it can help decrease impulsivity. “...the antisuicidal effects of lithium may work at lower levels than so-called therapeutic levels and not only in patients with mood disorders but also in the general population.” (Schrauzer, 1990; Terao, 2009)

We’ve also added hesperidin, a flavonoid widely found in fruits and vegetables for its ability to promote neurogenesis by enhancing the survival of neural progenitors that are developing into mature neurons. (Nones, 2012)

References

Montag et al. The role of the catechol-O-methyltransferase (COMT) gene in personality and related psychopathological disorders. CNS Neurol Disord Drug Targets. 11(3):236-50 (2012).

Zhu et al. Molecular modelling study of the mechanism of high-potency inhibition of human catechol-O-methyltransferase by (-)-epigallocatechin-3-O-gallate. Xenobiotica. 38(2):130-46 (2008).

Ericson et al. Taurine elevates dopamine levels in the rat nucleus accumbens; antagonism by strychnine. Eur J Neurosci. 23:3225-9 (2006).

Singh et al. Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition. Pharmacology. 68:81-8 (2003).

Nagai et al. Strong inhibitory effects of common tea catechins and bioflavonoids on the O-methylation of catechol estrogens catalyzed by human liver cytosolic catechol-O-methyltransferase. Drug Metab Dispos. 32(5):497-504 (2004).

Nones et al. Effect of the flavonoid hesperidin in cerebral cortical progenitors in vitro: indirect action through astrocytes. Int J Dev Neurosci. 30:303-13 (2012).

Schrauzer and Shrestha. Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions. Biol Trace Elem Res. 25:105-113 (1990).

Terao et al. Even very low but sustained lithium intake can prevent suicide in the general population? Med Hypotheses. 73:811-2 (2009).

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