Is Serum Uric acid a measure of Impulsivity ? Biol Psych.Jan.2014

09.01.2014

Impulsivity is a key component in many psychiatric disorders. Our current understanding of the physiological basis of impulsivity is limited. One such candidate is uric acid. It is observed that uric acid is elevated in pathological gamblers when they played for money but not when they played checkers without betting. Correlation with hyperactivity symptoms has been reported in children. Methylphenidate has shown to decrease uric acid levels parallel to improvements in symptoms. Individuals presenting with first manic episode is observed to have high uric acid levels. Behavioural manifestations of Lesch-Nyhan syndrome ( enzyme deficiency that causes a buildup of uric acid) include impulsivity.

Can uric acid levels be a marker for impulsivity?  Sutin et al examined the association between uric acid and impulsivity-related personality traits in two large longitudinal samples that included two assessments of uric acid measured approximately 3 to 5 years apart. They also looked in to effect of smoking,BMI, age , sex and psychiatric morbidity  in the relation between impulsivity and uric acid. Revised NEO Personality Inventory was used to assess impulsivity. Impulsivity is measured by four traits : impulsiveness (the tendency to give in to temptation); excitement seeking (the tendency to crave stimulation); self discipline (the tendency to follow through on intentions); and deliberation (the tendency to think before acting).In the second study they  study they compared the behavior of mice with elevated levels of uric acid (uricase-deficient mice) with that of wild-type mice.

Results

Individuals who were prone to give in to temptation (impulsiveness) and those who craved stimulation(excitement seeking) had higher levels of uric acid. Among the four impulsivity-related personality traits, uric acid was most consistently associated with excitement seeking. Lower self- discipline and lower deliberation were also associated with higher uric acid. Across the 3-year follow-up period, higher scores on excitement seeking and lower scores on deliberation were associated with increases in uric acid.

Smoking and/or BMI partially mediated the association between impulsiveness and uric acid levels . Higher uric acid may contribute to more impulsive behavior, including consumption of alcohol and soda, which, in turn, may increase levels of uric acid ( bidirectional relationship)

Excitement seeking was associated with increases in uric acid over the follow-up period. Controlling for psychiatric morbidity or removing participants with a history of psychiatric illness from the analyses did not alter the findings.

Mice study:  elevated uric acid levels  enhance exploratory and novelty-seeking behaviors in mice.

Conclusion

Impulsivity-related traits are associated with higher levels of uric acid in humans. Mice bred for high levels of uric acid displayed significantly more exploratory and novelty-seeking behavior than their wild-type peers.

Limitations: Impulsivity is a complex trait and it is likely the product of many genetic, environmental, and biological factor. Tasks used to measure impulsivity also reflect anxiety. Role of diet in this association not explored.Physiological pathways through which impulsivity and uric acid are linked is not known.

Explaining the link? Authors suggest that this may be evolutionary in origin. Uric acid may be a physiological alarm signal that evolved to arouse animals to search for food. After periods of fasting uric acid levels increase, and this rise is associated with increased foraging and food intake. This  was advantageous and perhaps helped us to survive  during periods of food shortages. The foraging/increased arousal that had purpose is continuing to be expressed through impulsive and novelty-seeking behavior.

Summary of the article:

Impulsivity is Associated with Uric AcidEvidence from Humans and Mice.

Sutin AR, Cutler RG, Camandola S, Uda M, Feldman NH, Cucca F, Zonderman AB, Mattson MP, Ferrucci L, Schlessinger D, Terracciano A.

Biol Psychiatry. 2014 Jan 1;75(1):31-7

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