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Twine.com - bookmarking and social networking

Friday, November 28, 2008

I'm experimenting with Twine.com, which is a newish bookmarking and social networking site. That is, it's a combination of Del.icio.us (and the like) and (a rather simple) Facebook sort of thing.

The social networking isn't anywhere as nearly comprehensive as Facebook, but it's the same idea. The bookmarking, on the other hand, is as spiffy as Del.icio.us and others of that genre, with extras.

Bookmarks are organizied into groups called "twines", which can be public or private, and typically cover some recognizable topic area, or whatever people want to use them for. Each bookmark can also have a description and any number of tags, specified by the user creating the bookmark. Each bookmark also allows for comments, which anyone may add.

Underlying all this is "semantic web" technology. It's a cool computer-sciencey set of concepts and conventions for organizing heterogeneous collections of data in a way that (supposedly) is easier to search and navigate than the existing anarchy of Web pages, blog posts, etc. But I'm still waiting to see some compelling practical results...

In any case, I've set up some twines that I will use for bookmarking interesting scientific articles I come across. These items tend to be fairly non-technical, intended for an interested but not highly specialized audience, rather than articles from professional, refereed journals.

If you follow any of the links below, you will have to register with Twine, and should then get to see the various bookmark collections. You may choose to "join" any of the twines, which simply means that the system will keep track of the ones you have joined so you can visit them later. There is an option for receiving email notification of additions to individual twines. You can start your own twines too, if you like.

The social networking part is that you can set up a personal profile for youself, with whatever information you are willing to share. You can find out which other users have joined the same twines as you have, and "connect" with them if you have shared interests, as on Facebook or similar systems.

So, this is just an experiment to see if there is interest in something of this sort for groups of bookmarks to possibily interesting articles that deal with many of the topics written about here. If there doesn't seem to be much interest, or if I find it's too time consuming to be worth the effort, I'll stop.

On the other hand, if people give it a try, suggesting bookmarks of their own that are appropriate for one of the following twines, if desired, then maybe the experiment will yield something worthwhile.

You can leave comments to this post if you have questions or suggestions. Alternatively, you can send messages to other users on Twine itself.

Current twines I've started:

Scientific Readings: Neuroscience

Scientific Readings: Medical Biology and Biotechnology

Scientific Readings: Physics

Scientific Readings: Mathematics

Scientific Readings: Astronomy, Astrophysics, Cosmology

Politics as beauty contest

Sunday, November 23, 2008

Perhaps interest in politics has dropped off a lot now that the U. S. elections are over (for this year). But there's still some interesting political science that came up before the big event.

Even though political scientists, year in and year out, are as busy publishing as any other kind, quite a number of research announcements were noted recently outside of traditional professional venues. That has tapered off now, but there were a number of items that seem to call for some comment here. So I'll do some of that despite what is bound to be a declining interest in the subject.

A perennial favorite of election-oriented political research centers around questions of how the appearance of a candidate affects electoral success. That's no different this year. Here's a fairly typical example:

A Pretty Face Can Make A Difference In Whom You Vote For (10/30/08)
According to new Northwestern University research, it is not at all surprising that everyone also is talking about the great looks of vice presidential hopeful Palin.

Whether or not you believe the McCain campaign's $150,000 expenditure for Palin's wardrobe and the much-talked-about salary of her makeup artist are over the top, the decision to play up the looks of the former beauty queen is a winning strategy.

Even in 2008, a perception of competence -- a strong predictor of whether people will vote for political candidates -- is not enough to give women the winning edge in political contests, according to the new Northwestern psychology study.

For both men and women, female political candidates needed to be seen as attractive as well as competent to get their votes. ...

While gender bias related to a female candidate's attractiveness was consistent across both male and female voters, good looks was almost all that mattered in predicting men's votes for female candidates. And, true to prevailing stereotypes, competence was almost all that mattered in predicting men's votes for male candidates.

The idea that good looks positively affects electoral success has been researched many times – as well as being often suspected by a lot of people who aren't professional – in all kinds of elections from student councils on up. I discussed one study on this in a post here almost 2 years ago.

The new research I want to examine here was not entirely, or even primarily, about the importance of attractiveness in winning elections. Instead, experimental participants were first asked to rate candidates independently, based on their photos, on four different attributes: "competence", "dominance", and "approachability", as well as "attractiveness".

The politicians in question were actually candidates in 2006 U. S. Congressional elections. The politicians' photos were then presented in pairs actually competing with each other. Experiment participants were asked to chose which of each pair they would vote for if the office were actually the U. S. presidency.

The resulting data were analyzed in various ways. First, in comparison of participants' voting choice to how they had rated the candidates on each of the four attributes. Second, in comparison of candidates' gender and facial appearance to actual Congressional election outcomes. And third, in comparison between how the candidates won or lost in the simulated presidential election and in the actual Congressional election.

Since I want to focus just on the attractiveness issue, I won't attempt to summarize all the results here. You can find the summary in the research paper itself (citation below). I'll mention only two specific observations: (1) "Female candidates were more likely to win votes if they were more attractive." (2) "Male voters were significantly more likely to vote for candidates that appeared attractive." (I presume these statements represent correlations between opinions of attractiveness and voting behavior of each experimental participant.)

Now, it may be true as the research asserts, that attractiveness matters more for female candidates, while a perceptions of "competence" is relatively more important for male candidates. However, the attractiveness of male candidates (especially in contests exclusively between two males) is a still a net positive.

There's another possibility that should be considered even when voters seem to make their voting choices based on judgment of "competence" of male (or female, for that matter) candidates. Namely, that "attractiveness" (perhaps in a form not consciously associated with the term) might bias this judgment. One has to wonder exactly what visual characteristics might signify "competence" to voters, and whether certain factors – such as a "strong jawbone" (for a male) – don't contribute simultaneously to judgments of both attractiveness and competence.

Humans are fairly sophisticated in making judgments about traits like "competence", since evaluations of other people's character and ability are important in deciding whom to trust. The ability to do this reliably has a lot of evolutionary importance. This doesn't mean people are infallible about such judgments – clearly they aren't. But people probably can do better than chance in making such judgments, at least when not faced with situations where the person being judged is skilled at faking appearances. Perhaps it's more a case of detecting lack of competence, as might be signaled by poorly managed facial expressions (e. g. simply looking perplexed or "stupid").

But judgments about good looks and attractiveness are even more natural. We make them all the time, hardly giving any thought to the matter. Research has shown that people tend to make judgments about facial attractiveness very quickly. (See here.) This suggests people tend to use simple heuristics that may well be hard-wired.

Research apparently shows that even babies prefer to stare at beautiful faces. Note, too, how illustrated children's literature (and now movies) usually portrays virtuous or heroic characters as beautiful or handsome, while evil or villainous characters are ugly, often very ugly, and much to be feared. So there may be an element of social conditioning here, at least for children beyond infancy.

An interesting observation in the report of the research just mentioned, about the quickness of making judgments, is that "It seems that pretty faces 'prime' our minds to make us more likely to associate the pretty face with a positive emotion." ("Priming" is a hot topic in current psychological research.) So, comparatively speaking, a face that isn't "pretty" would be associated with less positive emotions. That alone would be enough to influence voting choices, if "everything else" is assumed to be equal.

There are different possible factors that may enter into such a judgment. So let's consider further what factors and heuristics might be used in judging facial attractiveness. It would be quite interesting to know how the various factors about to be mentioned perhaps have different effects on political choice.

A small number of factors are often suggested. One of the oldest is that the property of "youthfulness" is associated with attractiveness. That makes plenty of evolutionary sense, as fertility, reproductive capacity, and ability to nurture children all decline with age after the beginning of adulthood. It should be noted that youthfulness should be especially salient in the judgment of young people – such as the experimental subjects (college students, average age 19.5) in the research under discussion

A more recent suggestion is that "symmetry" is important, as that would tend to indicate general healthiness. (Recent research here.) That makes sense, too, but does it have any reasonably apparent relevance to voting decisions?

"Symmetry" is probably a looser criterion than in an older and fairly well-known theory of attractiveness, often called simply the "averageness" hypothesis. This holds that average phenotypes in a population are judged more attractive than phenotypes with notably atypical features. An average value on a particular facial metric (such as width of nose or chin) is considered to be what is "normal", yet for most features all to be close to average might be fairly unusual.

So "averageness" is used in a somewhat special sense here – literally, as having size and proportion of most important facial features being close to the overall average. Probably faces that have "averageness" in this sense are fairly rare, which might add to the quality of "attractiveness". So "averageness" as a descriptor of faces is not the same as "common" or "ordinary" or "typical".

Since averages of many faces will wipe out most asymmetry (e. g. some part being off center), an averaged face will be symmetrical. So facial symmetry is a more common characteristic than averageness. A symmetrical face could still have features that are far from average values in size or position.

Since facial symmetry will be more common in a population than faces that have the property of averageness (in the special sense used here), averageness is a more stringent criterion for attractivness. Consequently, a voter who perceives one candidate's face as more attractive than the candidate's opponent is making a more significant discrimination, which could have higher weight in the final choice. Indeed, two candidates might have equally symmetrical faces, or at least faces that are difficult to distinguish in terms of symmetry, yet differ considerably in averageness and hence (perhaps) in attractiveness.

And so, to the extent that people actually judge attractiveness based on averageness rather than symmetry, it will be more likely that judgment affects a voting decision. In other words, we would expect on these general considerations that attractiveness is more likely to affect voting decisions if the criterion is actually "averageness".

There is some amount of research supporting the idea that averageness is the important criterion for attractiveness, such as findings that images created by averaging photographs of many individuals tend to receive higher ratings for attractiveness. So at least for the sake of discussion, let's assume there's some validity to this notion.

Deviations from averageness do not imply deviations from symmetry, so they would not be expected to have the stronger negative implications for overall health and (hence) fertility that asymmetry does, so there would be a smaller indication of "riskiness". It would therefore be harder to understand the evolutionary importance of judging the riskiness of another person based on attractiveness if averageness is the underlying consideration. Is it possible that averageness is important in judging riskiness for other evolutionary reasons – reasons that apply to evaluating others in more general contexts than the context of mate selection?

Yes, I think so. As I wrote in my previous post, "people who are considered attractive within a population are those who are most 'typical' or 'average'. Or inversely, least atypical, least different from the largest number of people in the population. People who are considered less attractive have facial features that vary a lot from the norm, such as lips that are too thin or too thick (compared to the average), eyes too far apart or too close together, eyebrows that are too sparse or too bushy."

The evolutionary rationale at work here is that people who appear too "different" from the norm are more likely to belong to a different, more genetically distant tribe. Such people are probably less likely to deserve trust, and might even be "dangerous".

I think this matter of perceived trustworthiness vs. potential "danger" in the eyes of voters could be rather important, especially if it is unconsciously inferred from perceptions of a candidate's attractiveness. I've written more on that here, not too long ago, so I won't repeat it now.

More generally, I see conscious and unconscious issues of fear and perceived danger as especially important factors in a voter's attitudes towards, and relationship with, government. This is because, as a matter of both philosophy and sociology, one of the primary reasons for the existence of governments is to "protect" citizens from a variety of potential evils, whether they be dishonest businesspeople, common criminals, foreign and domestic terrorists, or whatever. I've written a lot more about that here.

The question, then, is whether the research now under discussion supports the idea of a connection between fear and voting behavior, or is even relevant to it. To be honest, the relevance is somewhat tentative, since it relies on the idea that there is a negative correlation between the attractiveness of a political candidate and whether a voter feels fear associated with the candidate at some level. It would be very interesting to see more research that addresses this issue more directly.

Regarding the present research itself, I have a few reservations as well. For example, the experimental participants were university students of average age 19.5 years. Quite possibly many of the participants had never even voted in a governmental election, and they certainly did not have a few decades of adult experience – with politicians, elections, and actual government performance – that could shape and inform their voting decisions. It's not surprising that individuals with little adult experience would base decisions on appearance factors.

Aside from that, there's also the question of whether the socioeconomic demographics of university students would skew the results from what would be found in the electorate as a whole. And then there's the whole other issue of possibly relevant cultural differences between the U. S. and other democratic countries.

So there's reason to suspect that typical, experienced voters, even in the U. S., might produce rather different results in a similar sort of experiment.

Here's the research paper, with some of the abstract:

The Political Gender Gap: Gender Bias in Facial Inferences that Predict Voting Behavior
Contrary to the notion that people use deliberate, rational strategies when deciding whom to vote for in major political elections, research indicates that people use shallow decision heuristics, such as impressions of competence solely from a candidate's facial appearance, when deciding whom to vote for. Because gender has previously been shown to affect a number of inferences made from the face, here we investigated the hypothesis that gender of both voter and candidate affects the kinds of facial impressions that predict voting behavior.




ResearchBlogging.org
Joan Y. Chiao, Nicholas E. Bowman, Harleen Gill (2008). The Political Gender Gap: Gender Bias in Facial Inferences that Predict Voting Behavior PLoS ONE, 3 (10) DOI: 10.1371/journal.pone.0003666


Update on 11/24/08: I have extensively reworked the discussion about "attractiveness" and its relationship to "symmetry" and "averageness". One would like to see more experimental evidence to sort out these factors in general and specifically as to how they affect voting choice.

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Dopamine and obesity

Monday, November 17, 2008

Dopamine is a neurotransmitter that's well-known for its involvement in several notable medical and behavioral problems, such as Parkinson's disease and drug addiction. But it is connected with many other issues of medical and psychological importance.

Perhaps the main reason that dopamine is so interesting is that it plays a big role in the brain's pleasure and reward systems. And therefore it is inevitably involved in reward-motivated behaviors of all kinds, from gambling, investing, substance abuse, and sex, to – eating. After all, isn't a high percentage of behavior motivated by rewards? There are other motivations for particular behaviors – fear and physiological needs, for example – but reward covers an awful lot of it.

Consequently, problems in the reward system can lead to excesses in some behaviors (e. g., gambling, eating), and perhaps also deficiencies in other behaviors (e. g. loss of interest in normal pleasures, as might accompany depression).

And because of the importance of dopamine in the reward system, problems with dopamine signaling can lead to problems in the reward system, with predictable consequences.

In the research we're going to look at, dopamine signaling is impaired in the presence of a particular allele associated with the D2 receptor for dopamine (known as DRD2). The conclusion is reached via the observation of decreased activity, as mesured by fMRI, in a brain region called the dorsal striatum. It is known that the variant allele causes a lower density of D2 receptors in this region.

The bottom line of the research is that individuals with this variant allele tend to have impaired ability to enjoy rewards from foods that most people like, such as chocolate. As a result, such individuals are disposed to consume more food in order to achieve an acceptable level of satiation of reward.

It might be thought, instead, that since the desirable foods produce less reward in individuals with the variant allele, they might consume less, due to reduced interest. However, that's not how the reward system seems to work. It seems to require achievement of a certain signal level in order to reach satiation and thus decrease the motivated behavior.

This is similar to the way signaling works with another hormone connected with eating, namely leptin. Normally, leptin levels rise when food is consumed. There are receptors for leptin in the ventromedial nucleus of the hypothalamus, a region that is responsible for appetite. There leptin inhibits the activity of neurons that contain neuropeptide Y (NPY).

A connection has been found between obesity and insensitivity to leptin, much as diabetes results from decreased sensitivity to the hormone insulin. Preseumably, individuals with reduced sensitivity to leptin don't know when to stop eating. Much the same state of affairs seems to exist in individuals with the allele (which is a DNA restriction enzyme called TaqIA) that affects DRD2 receptor density in the dorsal striatum.

Obesity, Abnormal 'Reward Circuitry' In Brain Linked: Gene Tied To Dopamine Signaling Also Implicated In Overeating (10/16/08)
Using brain imaging and chocolate milkshakes, scientists have found that women with weakened "reward circuitry" in their brains are at increased risk of weight gain over time and potential obesity. The risk increases even more for women who also have a gene associated with compromised dopamine signaling in the brain.

The results, drawn from two studies using functional magnetic resonance imaging (fMRI) at the University of Oregon's Lewis Center for Neuroimaging, appear in the Oct. 17 issue of the journal Science. The first-of-its-kind approach unveiled blunted activation in the brain's dorsal stratium when subjects were given milkshakes, which may reflect less-than-normal dopamine output.


Here's the research paper, with abstract:

Relation Between Obesity and Blunted Striatal Response to Food Is Moderated by TaqIA A1 Allele
The dorsal striatum plays a role in consummatory food reward, and striatal dopamine receptors are reduced in obese individuals, relative to lean individuals, which suggests that the striatum and dopaminergic signaling in the striatum may contribute to the development of obesity. Thus, we tested whether striatal activation in response to food intake is related to current and future increases in body mass and whether these relations are moderated by the presence of the A1 allele of the TaqIA restriction fragment length polymorphism, which is associated with dopamine D2 receptor (DRD2) gene binding in the striatum and compromised striatal dopamine signaling. Cross-sectional and prospective data from two functional magnetic resonance imaging studies support these hypotheses, which implies that individuals may overeat to compensate for a hypofunctioning dorsal striatum, particularly those with genetic polymorphisms thought to attenuate dopamine signaling in this region.

The idea that problems with dopamine signaling might be related to overeating and obesity isn't new. The following research announced in July involved rats rather than humans and considered other dopamine insufficiency mechanisms, but the basic conclusions are the same:

Obesity Predisposition Traced To The Brain's Reward System (7/29/08)
The tendency toward obesity is directly related to the brain system that is involved in food reward and addictive behaviors, according to a new study. Researchers at Tufts University School of Medicine (TUSM) and colleagues have demonstrated a link between a predisposition to obesity and defective dopamine signaling in the mesolimbic system in rats.

The mesolimbic system is a system of neurons in the brain that secretes dopamine, a neurotransmitter or chemical messenger, which mediates emotion and pleasure. The release of the neurotransmitter dopamine in the mesolimbic system is traditionally associated with euphoria and considered to be the major neurochemical signature of drug addiction. ...

Pothos says, "These findings have important implications in our understanding of the obesity epidemic. The notion that decreased dopamine signaling leads to increased feeding is compatible with the finding from human studies that obese individuals have reduced central dopamine receptors." He speculates that an attenuated dopamine signal may interfere with satiation, leading to overeating.

Paper abstract:

Evidence for defective mesolimbic dopamine exocytosis in obesity-prone rats
In electrophysiology studies, electrically evoked dopamine release in slice preparations was significantly attenuated in OP [obesity-prone] rats, not only in the nucleus accumbens but also in additional terminal sites of dopamine neurons such as the accumbens shell, dorsal striatum, and medial prefrontal cortex, suggesting that there may be a widespread dysfunction in mechanisms regulating dopamine release in this obesity model. Moreover, dopamine impairment in OP rats was apparent at birth and associated with changes in expression of several factors regulating dopamine synthesis and release: vesicular monoamine transporter-2, tyrosine hydroxylase, dopamine transporter, and dopamine receptor-2 short-form. Taken together, these results suggest that an attenuated central dopamine system would reduce the hedonic response associated with feeding and induce compensatory hyperphagia, leading to obesity.


News reports of the human dopamine results:




ResearchBlogging.org
E. Stice, S. Spoor, C. Bohon, D. M. Small (2008). Relation Between Obesity and Blunted Striatal Response to Food Is Moderated by TaqIA A1 Allele Science, 322 (5900), 449-452 DOI: 10.1126/science.1161550


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Non-coding RNA and gene expression

Sunday, November 16, 2008

Human DNA consists of about 3.4 billion base pairs. A portion of that is actually genes that code for proteins required by human cells – roughly 20,500 genes. (See here.)

However, it's been recognized for a long time that only about 1.5% of human DNA (in terms of base pairs) actually codes for proteins. Little is known about the purpose (if any) of the remaining 98.5%, even though, by some estimates, 80% of human DNA is transcribed into RNA at some time.

This remainder is often called "junk DNA". But it's also known that a lot of it can't really be "junk", and must serve some useful purpose, because the sequences of large portions of it are highly conserved in evolution, being found almost unchanged in the genomes of human ancestors going back hundreds of millions of years.

Some of the 98.5% really does seem to be without useful function, consisting of stuff like transposons, which are DNA sequences that seem to be copied repeatedly and randomly into various parts of the genome (over evolutionary time spans)

The function of other portions of that 98.5% includes such things as introns found within genes, gene regulatory sequences, and "RNA genes" that code for various kinds of RNA that doesn't wind up being translated into proteins.

Such non-coding RNA can be further classified into things like ribosomal RNA, microRNA, small interfering RNA, and "long non-coding RNA".

This last, known as "long ncRNA" for short, is especially intriguing, because some studies have shown that there may be roughly four times as much of it (in base units) as there is of messenger RNA that is ultimately translated into proteins.

Even though a lot of these long ncRNAs are routinely found floating around inside cells, we're still in the dark about what, if anything, they actually do. But some recent research has revealed a little more about some long ncRNAs:

Early-stage Gene Transcription Creates Access To DNA (10/6/08)
Previously thought to be inert carriers of the genetic instructions from DNA, so-called non-coding RNAs turn out to reveal a novel mechanism for creating access to DNA required by transcriptional activation proteins for successful gene expression, according to Boston College Biology Professor Charles Hoffman, a co-author of the study with researchers from two Japanese universities. ...

Hoffman and his colleagues examined how the yeast cell senses its cellular environment and makes decisions about whether or not to express a gene, in this case fbp1, which encodes an enzyme. What they found was a preliminary transcription phase with a flurry of switches flicked "on" and then "off" as seen by the synthesis of non-coding RNA before the final "on" switch is tripped.

The non-coding RNAs initiate over one thousand base pairs of nucleotides along the DNA away from the known start site for this gene. The group discovered that the process of transcribing non-coding RNAs is required for the eventual production of the protein-encoding RNA. The transient synthesis of these non-coding RNAs serves to unfurl the tightly wound DNA, essentially loosening the structure to allow for gene expression. [Emphasis added.]

And here's the research article, with some of the abstract, providing a somewhat more precise description of what's going on:

Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs
Here we show that RNA polymerase II (RNAPII) transcription of ncRNAs is required for chromatin remodelling at the fission yeast Schizosaccharomyces pombe fbp1+ locus during transcriptional activation. The chromatin at fbp1+ is progressively converted to an open configuration, as several species of ncRNAs are transcribed through fbp1+. This is coupled with the translocation of RNAPII through the region upstream of the eventual fbp1+ transcriptional start site. Insertion of a transcription terminator into this upstream region abolishes both the cascade of transcription of ncRNAs and the progressive chromatin alteration. Our results demonstrate that transcription through the promoter region is required to make DNA sequences accessible to transcriptional activators and to RNAPII.

To expand on that just a bit, recall that chromatin is the form in which DNA is actually stored for safe keeping. It consists of the double-stranded DNA molecules wrapped around many protein complexes called nucleosomes. Before any stretch of DNA can actually be transcribed into messenger RNA, the DNA has to be unwound from the nucleosomes. The present research has determined that some long ncRNA takes part in this unwinding process.

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No more business as usual

Friday, November 14, 2008

A million thanks to SusanG at Daily Kos for mentioning this:

Obama's Victory: A Consumer-Citizen Revolt
As recently as this summer, while the economy unraveled (BusinessWeek, 7/14/08), I made two trips to Silicon Valley in the hopes of finding leaders who grasped the crisis—and the opportunity—inherent in the destruction of trust. I listened to Facebook executives but found them obsessed with how to monetize the site with advertising. Their users were not individuals, but "eyeballs." I asked Google (GOOG) CEO Eric Schmidt how he would develop and sustain the trust of his users. His response was to cite the provision of two classes of stock intended to insulate top management from investor pressures. I gave a talk on the crisis of trust. The response from self-described Internet court jester Esther Dyson was typical of what I had been hearing: "Personally, I'm not that concerned if people don't trust large institutions."

A few weeks later economic panic gripped the stock market. I flipped on ABC's Sunday morning news show with George Stephanopoulos only to hear economist Larry Summers explaining that the surprising depth of the economic meltdown was due to the loss of trust in institutions. What he didn't say was that this loss of trust is a vast sea whose level has been rising for decades. The subprime debacle and the ensuing credit freeze simply marked the moment when the sea wall was finally breached. ...

So can we invent a business model in which advocacy, support, authenticity, trust, relationship, and profit are linked? Can I write that sentence without invoking fear, disbelief, cynicism, or peals of laughter? The ugly practices that killed trust seem intractable to most people, whether they are the ones trapped inside the money machine or on the receiving end of its operations. But after this election, the answer to these questions has irreversibly changed. The answer today would have to be not only "yes we can" but also "yes we must."

No, this is not about "science" per se, unless one considers the philosophical side of economics (rather than the quantitative side) to be a science. Rather, it is the simple observation that anyone reading the daily news with an open mind can understand: Basing a modern large-scale economy primarily on the evolutionarily ancient motivation of greed and personal self-interest is not working out very well...

BDNF and depression

Tuesday, November 11, 2008

Back in March I wrote a little bit about the convoluted relationships among stress, learning, and memory (here). About the same time, I wrote about the relationship between memory and an important neural growth factor, BDNF (here).

It seems that BDNF is an important bridge connecting the topics of memory, stress, and depression. Back in March I also started to write more about how BDNF is linked to depression, but I got sidetracked. So the rest of this message is what I started to write about that connection, which is why the research covered is from March or earlier.

But before turning to that, it should be noted that there is more to say about the relationship between BDNF and stress, which I'll put off a little longer. There's also more to say about the relationship between BDNF and antidepressant drugs, some of which is more recent than March. I'll put that off too.

So let's just get into the older stuff about BDNF and depression, to start the ball rolling again.

Research has shown that one way in which BDNF is linked to depression is through the neurotransmitter serotonin – whose connection to mood, depression, anxiety, etc. is pretty well known (think Prozac).

In particular, BDNF seems to affect expression of the gene for the serotonin transporter (SERT). (The gene itself is called SLC6A4, which stands for "solute carrier family 6, member 4".) SERT is a cell membrane protein that transports serotonin from the synapse between neurons back into the neuron from whence it came – enabling "serotonin reuptake". Some forms of the gene for SERT seem to predispose individuals who carry it to mood disorder.

Here are some reports of recent research on BDNF, which give an idea of the variety of effects it has within the nervous system. (The summaries included here are mine.)


The yin and yang of genes for mood disorders (3/12/08)
This research studied conditions under which a variant of the gene for SERT (i. e. SLC6A4) predisposes the carrier to mood disorders. Apparently there are also at least two variants of the gene for BDNF. An individual with one form of BDNF is particularly susceptible to the deleterious form of the SERT gene, but with the other form of BDNF, an individual is completely protected against it.

Brain Chemistry Ties Anxiety And Alcoholism (3/4/08)
Production of BDNF is known to be stimulated by exposure to alcohol. The researchers in this study, whose leader author is Subhash Pandey, also knew from previous experiments that reduced levels of BDNF in the amygdalas of normal laboratory rats led to increased anxiety in the rats, followed by increased consumption of alcohol. The question was what happened due to deficiency of BDNF that increased anxiety, and how did consumption of alcohol reverse this effect by restoring BDNF.

It is also known that BDNF stimulate the production of another protein, Arc. If Arc could be suppressed in the amygdala even in the presence of normal levels of BDNF, and the rats experienced increased anxiety anyhow, this would show that it is probably a deficiency of Arc rather than of BDNF that is responsible for the anxiety. And indeed, when Arc was suppressed in spite or normal BDNF, the rats had higher anxiety. They also consumed more alcohol. But when Arc levels returned to normal, the anxiety returned to normal, and alcohol consumption did too.

The question then came down to how a deficiency of Arc increased anxiety. It was found that temporarily reduced levels of Arc resulted in reduced numbers of dendritic spines of neurons in the amygdala. Since axons of other neurons form synapses with dendritic spines, there will be fewer synapses when there are fewer spines. At the same time, anxiety also increased. Conversely, when levels of Arc returned to normal, either naturally or as a result of higher levels of BDNF due to alcohol consumption, the number of spines increased, and anxiety decreased. Once Arc had increased normally, alcohol consumption decreased too.

Earlier results: Brain Chemical Plays Critical Role In Drinking And Anxiety (8/8/06) – when expression of BDNF (which is regulated by CREB) is blocked, anxiety and alcohol consumption in rats increases.


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