Wednesday, 29 May 2013

Impulsivity and uric acid

A few years back I posted about an interesting body of research on purine metabolism in relation to the autism spectrum disorders (ASDs) and how some work from the likes of Mary Coleman and Ted Page had reported high levels of uric acid to be coincidentally present in cases of ASD.
The gout @ Wikipedia  

As with other research angles, the initial interest in this finding of hyperuricosuria - elevated urinary uric acid - and autism did not seem to last. Just like the dusty research doll that is sulphation (sulfation) and autism, uric acid came to find itself under the autism research bed listening to the tune of 'when somebody loved me'. Sulphation, I might add with autism in mind, has started to see something of a renaissance recently but only a small one (see here).

Enter then an intriguing paper by Angelina Sutin and colleagues* reporting on an association between elevated levels of uric acid and impulsivity as a trait in both human and mice. As per another recent paper which was discussed on this blog on ADHD and solar intensity, the publishing journal was Biological Psychiatry which is fast becoming a real favourite journal of mine. Reading through Dr Sutin's profile page it is interesting to note that she has some interest in how personality might be associated with physical and mental health. Her latest paper therefore continues this interesting theme.

A few details from the Sutin paper are in order:

  • This was a study drawing on both human and mouse model data to ascertain whether the findings of elevated uric acid in behavioural and psychiatric conditions "characterized by high impulsivity" might actually be specifically related to the impulsivity trait.
  • Human participants (N=6883) derived from two cohorts - SardiNIA and the Baltimore Longitudinal Study of Aging - completed the Revised NEO Personality Inventory which aims to characterise the Big Five personality traits (openness, conscientiousness, extraversion, agreeableness, neuroticism) via self-report.
  • They also provided fasting blood samples which were screened for uric acid both at time of schedule completion and at follow-up (some 3-5 years later).
  • A second study was also reported looking at the behaviour of mice "urate oxidase null" = bred to show elevations in uric acid, compared with wild-type controls. 
  • Results: lots of them, but a few of the more interesting findings included (i) impulsiveness and excitement seeking individuals were more likely to have higher levels of uric acid (albeit mediated by factors such as BMI and smoking which themselves pose some interesting questions), and (ii) "homozygous urate oxidase-deficient mice" (high uric acid) showed a lot more exploratory and "emotional" behaviour. 
  • In short, the two experiments reported "supports the hypothesis that impulsivity is associated with higher levels of uric acid".
  • Another quote from the paper sums up where this kind of research could potentially lead: "The identification of biological markers of impulsivity may lead to a better understanding of the physiological mechanisms involved in impulsivity and may suggest potential targets for therapeutic intervention".

Very interesting stuff I'm sure you'll agree. Indeed the participant numbers for the human part of the study are certainly impressive and indeed across the two geographically distinct cohorts too, even more impressive.

But with my science-hat on, lets take a step back and point out some important limitations of this work. First and foremost is the assumption that the personality trait impulsivity measured by only one personality inventory is the only potential correlate here, at least among the human participants. It isn't. And indeed one should always be mindful that just because investigators test for something like a personality trait or a specific cognitive skill or even a specific condition/state/disease does not mean they have excluded all other potentially important variables** (indeed if this is even possible). Next is the assumption that self-report responses on a five-point Likert scale are going to be true and honest. No-one can be totally assured of that, particularly if responses are to some of the more less desirable personality traits that we would all like to put to one side. Finally is the interpretation of a mouse model of high uric acid showing the impulsivity trait based on their novelty-seeking and exploratory behaviours during field tests. I've talked mouse models before with autism in mind and how behavioural animal models are always subject to some degree of interpretation until such time that we can talk to the animals (and they talk back).

Having said all that I do find myself still very interested in the Sutin findings in terms of how the work was done, the results obtained and where it could lead. Without giving anything that looks or sounds like medical or clinical advice, one has to wonder (as the authors have done) whether 'adjusting' levels of uric acid might have a knock-on effect on certain behaviours particularly where uric acid might be seen in more behaviourally or psychiatrically defined conditions. I'm not saying everyone should be taking something like allopurinol or anything like that but perhaps further investigation is at least warranted.

Finally, on a similar note to the Sutin study I also recently came across a study by Soto-Insuga and colleagues*** which reported some very preliminary findings from treating iron deficiency in cases of attention-deficit hyperactivity disorder (ADHD). To quote: "Treatment with iron supplements can be an effective alternative to treat patients with ADHD and iron deficiency, especially the inattentive subtype". By 'treatment' I take it to mean that not only were the authors resolving the iron deficiency but also in specific cases of ADHD identified by that inattentive subtype**** they were talking about the management of behavioural symptoms too.

Example evidence that the psychosomatic or somatopsychological relationship should definitely remain near the top of the research agenda?

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* Sutin AR. et al. Impulsivity is associated with uric acid: evidence from humans and mice. Biol Psychiatry. April 2013.

** Cerecero P. et al. Association between serum uric acid levels and cardiovascular risk among university workers from the State of Mexico: a nested case--control study. BMC Public Health 2013; 13: 415.

*** Soto-Insuga V. et al. Role of iron in the treatment of attention deficit-hyperactivity disorder. An Pediatr (Barc). April 2013.

**** Solanto MV. The predominantly inattentive subtype of attention-deficit/hyperactivity disorder. CNS Spectr. 2000; 5: 45-51.

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ResearchBlogging.org Sutin AR, Cutler RG, Camandola S, Uda M, Feldman NH, Cucca F, Zonderman AB, Mattson MP, Ferrucci L, Schlessinger D, & Terracciano A (2013). Impulsivity is Associated with Uric Acid: Evidence from Humans and Mice. Biological psychiatry PMID: 23582268