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Archive for May, 2009

Mike Defensor at a political rally in Cebu City
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Shopaholics and political activists might want to take a look at Jonathan Roiser et al.‘s paper, “A Genetically Mediated Bias in Decision Making Driven by Failure of Amygdala Control” [doi:] as an early example of the nexus of “behavioral-neuro-economic-genetics” or “neuro-genetic-marketing” or “neuro-eco-geno” as it might (not) be called one day.  In any case, it has long been known that humans are susceptible to the “framing effect” – that is – we favor certainty over risk when we stand to gain ($10 now vs. 20% chance of winning $50) and rather favor risk over certainty when we stand to lose (20% chance of losing $50 vs. lose $10 now).  Political and retailing experts have long-since exploited these tendencies in voters/consumers (unemployment is on the rise – lets take a chance on this new policy! or this yogurt is 99% fat free! vs. its got 1% of unhealthy fat).

Roiser and team evaluate the extent to which individuals who are homozygous at the 5HTT-LPR “short” allele differ from “long(a)” allele homozygotes when confronted with win/lose, sure-thing/gamble contingencies.  Interestingly, while both groups demonstrated the tendency to avoid risk when they stood to gain money and preferred to gamble when they stood to lose money, the group that was homozygous at the 5HTT-LPR was almost twice as likely to do so – thus identifying a group that is significantly more susceptible to the framing of choices (they otherwise did not differ from the “long(a)” group in control trials or in other aspects of overall performance).

Analysis of brain activity shows a now well-replicated association of “short”-allele genotypes with increased amygdala activity  – in this case the association was observed when participants were confronted with the choice of “pick the sure thing” vs. “gamble” in both the gain and loss conditions.  Also, the group reports on the functional coupling of the amygdala and cingulate cortex – an effect which has been previously associated with variation at the 5HTT-LPR – and shows that individuals who did not show functional coupling between these brain regions were more susceptible to the framing effect.  Hence, the “short” allele group may have a harder time bringing cortical control to their immediate emotional responses.

What might these findings tell us about decision making in humans?  Well, as pointed out by the authors, the findings in the amygdala and cingulate cortex suggest that the emotional systems of the participants are engaged as well as genetic factors, such as 5HTT that are known to regulate the early development and responsivity of these emotional systems.

Most of us already know that we don’t make decisions only using our minds – and doncha know – retailers and political pollsters are already experts at gaming our innate propensities.  Some, it seems, perhaps more than others.

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Petter Solberg driving a Subaru at the 2006 Cy...
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Just joining in on the “blog rallyas per Scott Shreeve’s suggestion.  I hope team Orszag will follow the contest with interest.

-join the rally & raise awareness for this topic!

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Richard Westall, The Sword of Damocles, (Briti...
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Just having some fun with SNPedia’s new release of Promethase (0.1.66) which now has a superfast analysis option ($2 via a link to your Amazon.com account) as well as the usual free regular speed option.  I had some fun comparing my 23andMe profile to my wife’s using the experimental “breeding” tool and – 214 seconds later – had a glimpse of the genetic probabilities that now hang like the Sword of Damocles over my children. A few SNPpets include:
rs1726866(T;T) – unable to taste bitter 80% likely to be unable to taste bitter
rs10246939(T;T) – unable to taste bitter
rs11200638(A;A) – ~10x increased risk of wet age related macular degeneration
rs7754840(C;C) – 1.3x increased risk for type-2 diabetes
rs324650(T;T) – higher IQ The rs324650(T;T) genotype boosts intelligence
rs2802288(A;A) – longer lifespan
rs1815739(C;C) – possibly increased sprint/power performance

Although I won’t be around to vouch for the longer lifespan, I can vouch for the insensitivity to bitter taste (both kids love broccoli) and our torn up furniture must confirm the tendency to sprint muscles … as for the others, I guess we’ll see in time.  Thanks SNPedia!

(+2 points for mixing references to 2 Greek myths in 1 blog post)

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homebrew comics 6

Monetary vs. fiscal policy. Oh crap.

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homebrew comics 5

fanny and freddy ponder macroeconomic doom

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Ashoka tree
Image by dinesh_valke via Flickr

from the Ashoka website … Ashoka’s Changemakers and the Robert Wood Johnson Foundation have launched a global search for “nudges” – innovative little pushes that help people make better decisions for their own health and the health of others.

2 finalists are working in the area of mental health:

Congratulations to Depression “nudge” and Room makeover

You can vote for a winner among the 10 finalists!

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Haroun and the Sea of Stories cover
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Recently, I’ve been reading Brian Boyd’s new book, On the Origin of Stories, – a lengthy work that relates human evolution to our creative processes.  This line of inquiry is closely related to an interest in genetics and brain function, since links between genetic variation and brain function can be used as a starting point in phylogenetic analyses and explorations into the origins of human nature.  Human(ist)-specific genetic variants … hmmm … easier said than done – I know.

One reason why this topic may be especially complex are the very deep phylogenetic roots to human emotional regulation.  Indeed, the emotions, although we might construe to be aspects of mental life, are rather much more aspects of our physical life.  As Pliny the Elder pointed out when he opined “A merry heart doeth good like a medicine“, there is an obvious 2-way relationship between the our physical state (heart function for one) and our mental state.  Thus, our understanding of the origins of human nature (or stories, in the case of Brian Boyd) may involve deep-rooted phylogenetic explorations that dig well before homo sapiens related its first tales.

How far back?  Perhaps the paper by Porges,  “The polyvagal theory: New insights into adaptive reactions of the autonomic nervous system” [doi:10.3949/ccjm.76.s2.17] offers some advice.  He suggests that the regulation of cardiac function has been adapted within mammals to support the 2-way communication of facial expressions and heart function. To quote from Porges’ article, “A face–heart connection evolved as source nuclei of vagal pathways shifted ventrally from the older dorsal motor nucleus to the nucleus ambiguus. This resulted in an anatomical and neurophysiological linkage between neural regulation of the heart via the myelinated vagus and the special visceral efferent pathways that regulate the striated muscles of the face and head, forming an integrated social engagement system.”  More specifically, he seems to point to the myelination of the mammalian vagus nerve (other vertebrates have an unmyelinated vagus).

This is a loooong way back in evolution.  Still, it is a story well worth telling.

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homebrew comics 4

Brain freeze

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brain_helix_stairs

Thanks, de3ug & RH

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whcc europe 2008 021
Image by Lloyd Davis via Flickr

Just enjoyed Uwe Reinhardt’s lecture on the current and future economics of healthcare in the U.S. and was very much struck by his emphasis on evidence-based medicine (predicts a potential 30% savings in Medicare spending) as a means to rid the current system of overspending.  A must-see, is the telling graphic showing how the northwest has vastly lower costs/enrollee than the rest of the country – this, he suggests, is where the Obama administration will focus their reform efforts.  Seems like basic science (which is oft blamed for raising the cost of healthcare) may yet be deployed to improve outcomes and keep costs in-line.

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A grandmother with her granddaughter
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Among mammalian species, moms can have it rough. THEY do the foraging and the child rearing usually without the help of dad who may or may not be prancing about defending his territory or doing who knows what.  The biological systems that manage such a predicament for the female would, not surprisingly, be highly regulated and, I imagine, a major target of natural selection.  For example, conflicts between what’s best for the offspring and what’s best for mom could drive the evolution of genetic and epigenetic mechanisms that counter-balance the tendency of moms to conserve resources and for offspring to use resources.  One such epigenetic mechamism that has been implicated in parent-offspring conflict is so-called genomic imprinting – wherein certain epigenetic marks (methylation of C*pG’s in many cases) leads to the expression of genes a parent-of-origin-type manner (eg. the gene inherited from mom might be expressed while the gene inherited from dad would be transcriptionally repressed).

With this link between epigenetics and maternal investment in mind (and with Mother’s Day around the corner) I enjoyed the recent paper, “Lasting Epigenetic Influence of Early-Life Adversity on the BDNF Gene” by Roth and colleagues [doi: 10.1016/j.biopsych.2008.11.028] where they measured the relationship between BDNF expression and methylation as a function of maternal behavior (in stressful and non-stressful) conditions.  Like many other neuronally-expressed genes, stress seems to lead to more methylation, which can – sometimes – interfere with transcription.  In the Roth et al., paper, BDNF seems to show this pattern as well since BDNF was downregulated about 50% in the prefrontal cortex of rat pups who were reared under stressful conditions.  Concomitant increases in methylation in the pups (which was blocked with methyltransferase inhibitors) was examined as a possible reason for the BDNF downregulation.  Most interestingly, the female pups who were raised by stressed moms – were themselves lousy moms (demonstrated poor licking and grooming behavior) and gave birth to pups (granddaughters) who also bore similar epigenetic marks on BDNF.

Is this maternal-care/epigenetics phenomena related to parent-offspring conflict?  Perhaps so, or perhaps just a spandrel or an unintended consequence of other levels of regulation.  It will be fun to explore this further.  Until then – be sure to thank your GRANDmother on Mother’s Day! – or not, if your are poorly groomed.

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Rhesus Monkeys
Image by Ginger Me via Flickr

As I and many other 23andMe participants begin to confront our genetic innards, we will likely ask whether any of the information is predictive.  Can we expect to read-off our genomic information and say, “I have risk for this, this, and this, and so I’ll change my life to compensate ?”  Certainly, in the area of mental health, there are genetic variants that confer bits of risk toward anxiety, depression, cognitive decline etc., but does the raw genomic information – alone – form a basis for diagnosis and proscriptive change?  In most cases, NO.  Rather, the genome is not unlike a plant seed, that will produce full leafy greens in rich soil, but merely a few buds in poor soil.

A great example of this can be seen in the recent paper, “What is an “Adverse” Environment? Interactions of Rearing Experiences and MAOA Genotype in Rhesus Monkeys” by Karere er al. [doi: 10.1016/j.biopsych.2008.11.004].  In this paper, they compared the emotional development of rhesus monkey infants (n=473) who carry different versions of an MAOA promoter polymorphism – so-called ‘low’ vs. ‘high’ transcriptional level alleles – and also who were reared in different social contexts.  Some of the existing literature on MAOA-environment interactions suggests that abuse or neglect during childhood predisposes individuals who carry the ‘low’ allele (this allele leads to less MAOA protein and less catabolism of 5HT and DA).  In this study, the environment was varied according to numbers of social companions and physical size of the neighborhood – (i) a field enclosure with up to 150 mixed adults & children, (ii) corncrib enclosure with 1 adult male, 2-5 females and various child playmates, (iii) mother-only small enclosure, and (iv) no-mother nursury rearing.

Which environment led to the emotional reactivity (anxiety, aggression etc.) that has been previously associated with the MAOA ‘low’ allele?  Interestingly, it was not the wild & wooly ‘field enclosure’ where infants can interact in a rich, species-typical manner.  Rather, it was the MAOA ‘low’ genotypic infants raised in the smaller groups who showed more signs of emotional reactivity, with cage-mother-only-rearing being the most extreme group.  The authors note that this finding may alter our expectations about what type of environment is optimal vs. adverse and suggest that in the smaller enclosures, the relative isolation underlies the development of anxiety.

From a more general perspective, this study raises questions about how we – humans – should interpret our genomic information.  What environmental conditions enhance or protect us from the potential genetic risk we carry?  How did my early rearing interact with my MAOA allele?  Something to discuss on Mother’s Day.

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