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Archive for the ‘TPH2’ Category

Dear Mrs. Jones,

The genetic profiling results show that your son carries 2 copies of the so-called “short” allele at the serotonin transporter linked polymorphic region (5-HTTLPR) and also 2 copies of the T allele of the G-703T polymorphism (rs4570625) in the tryptophan hydroxylase-2 (TPH2) gene.

Some studies find correlations between this genotype and higher amygdala activity – which, in turn – has been correlated with a number of anxiety-related traits and disorders.

In short, you may wish to expect that your son may grow up to be slightly more shy, bashful, diffident, inhibited, reticent, shrinking, hesitant, timid, apprehensive, nervous, wary, demure, coy, blushing, self-effacing, apprehensive, fearful, faint-hearted, wimpish, mousy, lily-livered, weak-kneed, unsure & doubtful.

Congratulations!  He will be a handful to raise as a child but one day make a great scientist, and an even better science blogger.


* thanks fyns for the pic.

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Lollipop-Nosed
Image by `michelleBlack via Flickr

“There is a sucker born every minute”, were the words that looped through my mind on the long train ride home after losing $200 in an unfortunate encounter with a card shark over on Canal Street, many years ago.  I recall that when the card shark (actually a kindly old man) suggested to me that I would easily outwit him and $$ win $$, I have to admit that I really, sort of, well, believed him.  Hmmm, what a sucker indeed.  Come to think of it though, he didn’t even know that I was a GG homozygote at rs4570625 in the tryptophan hydroxylase-2 gene, which according to Furmark and colleagues,  is “a significant predictor of clinical placebo response“.  Lucky for him I guess.

There is actually a lot of mainstream neuroscience research on the placebo response – for good reason – it has a way of complicating & inflating the cost of clinical trials for many neuropsychiatric disorders, but also shows that “overt suggestions” and non-medication-based talk therapies can lead to outcome improvement.  In any case, whether you prefer medication or non-medication modalities of treatment, there is much to be gained from understanding the basic biology of the placebo response. A great review on the biology of the placebo response can be found here.

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inside my brain
Image by TheAlieness GiselaGiardino²³ via Flickr

Every student can recall at least one stereotypical professor who – while brilliant – kept the students amused with nervous and socially inept behavior. Let’s face it, if you’re in academia, you’re surrounded by these – uh, nerds – and, judging by the fact that you are reading (not to mention writing) this blog right now – probably one of them. So, its natural to ask whether there might be a causal connection between emotionality, on the one hand, and cognitive performance on the other. Research on the neuromodulator serotonin shows that it plays a key role in emotional states – in particular, anxiety. Might it exert effects on cognitive performance ? In their paper, “A functional variant of the tryptophan hydroxylase 2 gene impacts working memory: A genetic imaging study“, (DOI: 10.1016/j.biopsycho.2007.12.002) Reuter and colleagues use a genetic variation a G to T snp (rs4570625) in the tryptophan hydroxylase 2 gene, a rate limiting biosynthetic isoenzyme for serotonin to evaluate its effect on a cognitive task. They ask subjects (who are laying in an MRI scanner) to perform a rather difficult cognitive task called the N-back task where the participant must maintain a running memory queue of a series of sequentially presented stimuli. Previous research shows that individuals with the GG genotype show higher scores on anxiety-related personality traits and so Reuter and team ask whether these folks activate more or less of their brain when performing the N-back working memory task. It turns out that the GG group showed clusters of activity in the frontal cortex that showed less activation than the TT group. The authors suggest that the GG group can perform the task using by recruiting less of their brains – hence suggesting that perhaps there just might be a genetic factor that accounts for a possible negative correlation between efficient cognitive performance and emotionality.

My 23andMe profile shows a GG here – nerd to the hilt – what will I use the rest of my PFC for ? Something else to worry about.

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