"Of Course!"

Road Signs for Meditation

The Physical Diversity of Uralic Speakers

The Uralic language family has always intrigued me. Partly it's because some people think that there is a Uralic substrate to proto-Germanic (see Kalevi Wiik); partly it's because Uralic speakers live in the center of a continent that is at once the center of the Old World, and in many ways not thoroughly explored with its interior still largely wild and uninhabited. But it's really intriguing to see how different Uralic speakers look from one another. They range from blonde, Scandinavian-looking, about-as-white-as-you-can-get Finns and Saami, to very Asiatic-appearing Nenets people in north central Siberia. Is this because there really aren't many genes for face shape, eye shape and hair type - that is, if you looked at, say, Germans and Spaniards genetically, are they genetically as distant on average as Finns and Nenets (just a few genes) but the differing German and Spanish genes don't happen to all be represented in easy-to-spot features? Or is there really a greater genetic distance? In which case, are these people whose ancestors adopted the language, or were they such a small group of hunter-gatherers running into big Turkic and Indo-European populations that their genes were swamped by whoever they met?

The interesting thing is that here the Urals form a fairly clear boundary for these genes. The Udmurts to the west (one of the groups above) are famous for being the most red-haired people on the planet, while on the other hand it's not hard to imagine that the Nenets family above is related to Native Americans and Inuit. (The Udmurts are the first one and the Nenets second, but I probably didn't have to tell you which are which!) But of course there is still cross-over between the two, and it's interesting precisely because most of us in the U.S. don't see these traits represented in the same people very often.

Does Mindfulness Act Through Modulation of Serotonergic Circuitry?

Investigating the connections between mindfulness meditation and the brain's serotonergic systems seems like a promising avenue of research. Mindfulness may be a way to directly influence this system based on observations from several domains.


1) A bedrock principle of psychopharmacology is that increasing the amount of serotonin in synapses improves depression and anxiety.

2) Acute doses of HT2A agonists (e.g. psilocybin) can also improve depression. These agents produce brief and intense sensory experiences. At low doses, subjects do not report hallucinations, but do report that sensations seem more intense and more affectively pleasant (e.g., colors are brighter).

3) Mindfulness, which is focused concentration on sensory input, has been shown to be effective in reducing depressive symptoms in RCTs (van Aalderen et al 2011).

4) Therefore, concentrating on sensory input as with mindfulness may produce similar effects to the SSRIs and HT2A agonists, mediated by the same pathway.


In a sense, giving SSRIs (or the more powerful one-time punch of psilocybin) may produce an exogenously-created mindfulness. No research has yet been done on the involvement of serotonergic circuitry with mindfulness meditation's effects.

Many of the measures correlating mindfulness meditation to outcome concern decreased rumination. To that end, the introspective among us should take note of this quote from a 2013 paper by Paul et al in Social Cognitive and Affective Neuroscience: "Our results suggest non-reactivity to inner experience is the key facet of mindfulness that protects individuals from psychological risk for depression."

What Is the Process By Which "Standard of Care" Improves Over Time?

There is a fantastic post up at Slate Star Codex that I can't recommend enough (both the post and the blog as a whole). In it, the resident physician writer notes that it's unclear how new information is evaluated and adopted as standard-of-care. He gives an example of a now-poorly-supported medical theory (MS caused by poor circulation), a current case where the jury is still out, and a case where a new treatment seems to have very solid data - but is still anything but mainstream medicine. For my fellow psychiatrists, that last one would be the use of minocycline for negative symptoms of schizophrenia. (The writer says no psychiatrists he knows have heard of this but at my institution it's starting to be discussed; however I've never seen anyone started on it for negative symptoms.) The concern is really this: isn't it possible that a potentially valuable publication will languish in obscurity, never to be replicated and built into the evidence-based pantheon? My suspicion is that these things start getting to patients as soon as insurers' and institutions' formularies adopt them, and that medical education and dissemination by journals and conferences is only secondary (apart from the extent to which those things influence formularies.)

Of special importance, this article also makes a point of demolishing the slopping thinking that private sector drug development somehow "suppresses" new treatments that don't make money. That's false. What they do is un-suppress treatments that they think will make money. Before medical school I had a twelve-year career as a drug development consultant, running the studies that would un-suppress drugs, and I find it very frustrating to hear the bias in academia against an enterprise that has done so much good for so many patients. The reality is that drug companies do not suppress or distort information, but they do decide based on a profit motive what information to pursue in the first place. As with all science, each study is a move that decreases uncertainty - about efficacy and safety of each treatment. You have to decide what the marginal value of that uncertainty decrement is, based on some combination of patient suffering and money. And of course that value will be different if you're part of a for-profit company, or an academic institution. As with most things, any narrative that tries to reduce this to a more-neatly-worldview-fitting left-right political angle is at least oversimplifying to the point of incoherence, and more likely just flat out wrong. That is to say: if your claim is that big bad regulations are what make drug discovery difficult and the government is in the way of patients and profits, you're wrong, just like you're wrong if you think that big bad drug companies somehow suppress the truth.

Finite Willpower and The Dual-Self: Behavioral and Imaging Evidence

More evidence that ability to choose delayed gratification (i.e., willpower) is a limited resource. The interesting thing here is the relative activity of the dlPFC. Choosing delayed gratification is associated with activation of a network including the dlPFC, and inactivation is associated with more present-orientation. Demand-avoidance (avoiding tasks which tax willpower) is also associated with low willpower.

Of course the obvious eventual application of this research is to make people behave more rationally by increasing their willpower and therefore the future orientation of the actions they choose. The next step is to understand the mechanism of willpower depletion. Interestingly, in exercise science, there is speculation that what accounts for the latent period between high-impact weight lifting sets is neurotransmitter depletion in the synapse, and restoration on the order of minutes by vesicular transporters. There is also some evidence that neurotransmitter re-uptake inhibitors (specifically SSRIs) can increase the amount of exercise that can be performed until exhaustion (specifically, distance-to-exhaustion in distance runners in my own correspondence). The same thing might be happening in the dlPFC network required for willpower. An initial investigation might be to pharmacologically manipulate neurotransmitter concentration in the synapse in animals models and look at the effect on delay of gratification.

Citation: Kool W, McGuire JT, Wang GJ, Botvinick MM (2013) Neural and Behavioral Evidence for an Intrinsic Cost of Self-Control. PLoS ONE 8(8): e72626. doi:10.1371/journal.pone.0072626

Rhesus Macaques Show St. Petersburg Lottery-Like Behavior

From a PNAS paper by Yamada et al. That is, the macaques were willing to take greater risks for a reward when their pre-existing "wealth" is greater, and the possible lost utility is therefore relatively smaller. The wealth in this case was water - either in the form of a drink of water, or their internal store of water as measured by blood osmolality (the macaque's water bank account). More applications of the St. Petersburg lottery here.

Yamada H, Tymula A, Louie K, Glimcher P. Thirst-dependent risk preferences in monkeys identify a primitive form of wealth. PNAS. Published online before print September 9, 2013, doi: 10.1073/pnas.1308718110.