Is creativity an illness? But then... what is an illness?

Are you creative? Do you ever feel that when your creativity strikes you become absolutely compulsive about your "inspiration," and totally depressed when, for some reason, your inspiration wanes? It always strikes me to read about how some of the most beautiful works of art were created: their creators were obsessed, compulsive, borderline dysfunctional. Gabriel Garcia Marquez sold his car and had his family live on credit for eighteen months so he could write One hundred years of solitude. Brunelleschi's obsession was the dome of Santa Maria del Fiore, Antoni Gaudi's obsession was La Sagrada Familia. It seems to me that obsessions may ruin your life (or most likely the life of your closest ones) when you have them, but they may also lead to the most wonderful things.

So, is creativity a good thing or is it an illness?

My friend and collaborator Tanmoy Bhattacharya brought to my attention an interesting BBC post that discussed the issue. The article came up in a Facebook discussion because it raised the question: "How do you define illness? When, exactly, does a behavior trespass the normality threshold and becomes an illness?" I really liked Tanmoy's take on the issue, and I asked him permission to repost it here on the blog. It's the best thing I could get since he won't do a guest blog for me. :-)

I think he raises excellent points on the complexity of the brain, its stimuli as well as its constraints. I enjoyed reading it, I hope you will too. And if after reading this you have questions for Tanmoy, go ahead and post them in the comments and I will forward them to him.

TB: In a system as complex as the brain, which interacts with such diverse environments, it is difficult to define health and disease. There has been a long standing hypothesis that certain brain functions like deductive logic and creativity are kept in check evolutionarily because the same "structure" that can give rise to very highly creative adaptations in one environment would give rise to maladaptive behavior in a different environment. The interest in the research is, therefore, understanding the architectural limits on the brain, not to stigmatize writers or expect every bipolar to pen out a story about an old man and the sea.

EEG: That's a very interesting theory. All greatest masterpieces required such great energy and dedication from their creators that these individuals had to, at some level, become unsociable, as focused as they were on their creation. I can see how, at a species level, "being socially fit" puts a constraint on the amount of time and "obsession" the brain can dedicate to a certain task.

TB: I do not believe that we yet have a definition of illness which is "biologically" meaningful. Sure, there is a diagnostic manual that tells a doctor today when to diagnose a particular mental illness, but it is more an expression of "social" reality than a "biological" reality. So, for example, the discussion of whether homosexuality is a disease is not argued on any grounds about what it does or does not do to the person, but rather whether the majority of doctors consider it within the "normal" spectrum of behavior. No wonder its classification changed from a disease to a non-disease as the social acceptability of homosexuality grew: not because such acceptance lessened the mental load on the person with the trait (it is now not considered a disease even when the person with the trait lives in a non-accepting community), but because it became "socially" acceptable as a "normal" behavior. Currently, there is a similar debate about whether bereavement distress should be considered normal even when it leads to behavior sufficiently aberrant to otherwise merit a diagnosis of clinical depression. In other words, the question is not whether the person is depressed after a loss: the question is whether it is a disease (possibly temporary like say getting the 'flu is a disease) or whether it is not a disease because it is "normal". The classification is not done based on any kind of biological reality, except whether it is considered normal; which is determined by methods of social science, not biology.

Does this concept of normality depend on a biological reality? In other words, is there a way, other than surveying doctors (the social science method), to figure out whether some one is abnormal? Remember that we know pretty much that all of us are different in many ways, if you defined me abnormal simply because I am unique (which I certainly am), then everyone would be abnormal. One could always say that one should not look at the totality (which made everyone unique), but trait by trait, and ask whether I have traits that very few other people have? Defining abnormality this way would, of course, make Picasso abnormal; but during a mass hysteria, it would classify everyone as normal. We again see that this definition fails to capture the abnormality that is relevant to defining disease.

I claim that the only way people have found to capture the relevant abnormality is by taking the design stance: human brains (and bodies) are supposed to be "for" something. When the organ (or the totality) is carrying out this function, it is normal; when it fails to carry out this function, it is abnormal. Note that this does not solve the underlying problem: someone still has to define the function, but that turns out to be an easier problem.

We could define a disease objectively as a malfunction if we could define function objectively. And, here, biology can bring an insight: the function of brains (and bodies) is to survive and use the environment, physical, biological, and social, to further the fundamental goals of long term survival of the traits. This is usually called reproduction, but it is far more subtle: for example, one can help raise grandchildren and contribute to the long term survival; under appropriate conditions, one can help other helpful members of one's community to help survival of the helpfulness trait. The mathematics is not simple, but recent work has made much of this clearer, and it is far more than pure reproduction. The part relevant to this discussion is that for a social animal this survival depends a lot on social calculations as well as other considerations.

So, then, we can define function as being able to properly calculate and take appropriate action; but that depends on the environment one faces. The same trait of fast decisive action to take the life of an unexpected person is wonderful in times of violent combat but completely malfunctional in a peaceful society. Similarly, it is easy to show that a mental make up that helps everyone, whether or not they are helpful to others, is malfunctional in the sense that it does not help its own survival except in societies that pays a high moral premium on that. Now, since most traits will find themselves in various environments, the malfunctional has to be defined as an intermediate: it should not be "fatal" in any of the environments that an individual is likely to face. But, this depends on the environments one is "likely" to face.

Given this situation, therefore, most traits tune themselves to intermediate values, because extreme values are typically extremely ill suited in some environments one is likely to face. And, all this is further constrained by the possible organization of the brain: for example, it is completely possible that the brain is composed of two parts, one that can analyze and model its environment in terms of an "open-loop" system controlled by impersonal physical laws which constrain and guide change, and a social system that can alternately assign agency (or "will") to parts of the environment. If this simple separation of thought patterns is an useful approximation, the division of resources between the two will affect a lot of behavior: a lot of resources devoted to the physical system will make one unable to understand complicated social dynamics; whereas too high a reliance on the social system might make one unable to understand that physical phenomenon often do not have wills and desires. Both of these taken to an extreme are obviously malfunctional, and, therefore, diseased: one can think of autism or schizophrenia as examples illustrating such symptoms. But, where exactly one stops being analytical and starts being high-functional autistic will depend on what environment one is defining with respect to: when the norm is highly complex social environments, one will probably classify some highly analytic people as diseased because they cannot function in society (i.e., the "mad scientist" or "computer geeks" will get classified as "mad" or "autistic"), whereas when complex physical systems but with little social structure are the norm, some people who see willful patterns in the universe will find themselves considered ill (e.g., a "religious fanatic" will be considered "mad").

So, what have we done through all this argument? We started by arguing that DSM (diagnostic manual) definitions depend on a certain standard of normal and are not objective. Through the chain of arguments, I have tried to establish that the former (i.e. dependence on the standard of normal) is inherent part of the problem, and cannot be removed except in the trivial sense that some things have never been normal. I have also argued, however, that this dependence does not need to be subjective: what is important is not what the "doctors" have experienced as normal, but rather the environments that the *person* being diagnosed has experienced and is likely to experience.

The interesting question is that supposing we take a bunch of brains and tune up their creativity (by changing whatever neurotransmitter chemistry or electrochemical connections that we need to). Now, in some environments and depending on the rest of the circuits in the brain, this will work perfectly fine and be very useful in understanding and modeling otherwise-hard-to-model systems (somewhat similar to a physical effect called "annealing"). If the same tuning is done to a different brain which does not have the same set of controls, this tuning could lead to a bipolar disorder. Basically this hypothesis would say that creativity needs to be balanced by other control systems, so any means of independent inheritance will quite often lead to getting the creativity structures without the control structures, leading to madness. Under this hypothesis, creative people are not insane, but biology would dictate that they are at a higher risk of having insane relatives (children/siblings/etc.) than less creative people.

But, there is a different possibility as well: the "control" unit hypothesized in the previous post may not be inherited much, but developed based on experiences; or its need may be dependent on the environment. In this case, the only difference between creative people and people with some forms of insanity would be the environments they have faced or will face. Creative people can then look at bipolars and paraphrase Bradford "But for the grace of environment, there go I". We do not know if either of these hypotheses are correct, but I hope I have explained why I find it interesting to ask these questions, and why the data presented in the article is consequently interesting.

Healthy habits are easier when you stop thinking about it

Raising health awareness has done little so far in actually improving global health. Humans seem to be stubbornly attached to certain behaviors, even when fully aware that such behaviors pose a health risk.

Currently, the four most prevalent noncommunicable diseases are diabetes, cardiovascular disease, lung disease, and cancer. The risk of death from any of the four can be significantly lowered by changing basic behaviors such as lowering the consumption of calories, alcohol and tobacco, while increasing physical activity and the consumption of fruits and vegetables. It sounds simple, in theory, but certain behaviors are so engrained in the society that despite widespread campaigns, we still haven't been able to change people's habits. And not surprisingly so, since much of our behavior is often automatic rather than dictated by consciousness. As Marteau et al. state in [1], not even personalized risk assessments like gene variants and other biomarkers have succeeded in dissuading people from certain behaviors.

We are complex beings, constantly shifting from full awareness and reflective, goal-driven behavior, to more automated actions where deep thoughts are far removed. The former behavior is more costly in terms of metabolic resources and energy. The latter is more efficient in our daily routine, but it has the disadvantage of taking over even when the consequences are undesired. For example, lab animals that have been trained to repeat certain behaviors, they will keep repeating them even when unpleasant consequences are introduced in the experimental setting. Therefore, in order to prevent noncommunicable diseases, Marteau et al. argue that we need to target automatic behaviors rather than conscious ones.

How can this be achieved?

Well, for example making fruits and vegetables very easy to find at the store, and relegate the so-called junk food to some hidden, desolate aisle that requires extra walking to get to. Also (and I know I'm totally going against common economy rules here), making fruits and vegetables cheaper than junk food would cause a huge switch in people's eating habits. If this may sound much of an utopia (yeah, I can see that), here are a few more practical things that can be changed: make stairs accessible from everywhere in a building, and hide the elevators. Make the elevators really slow that it's a lot more practical to take the stairs. Make tobacco and alcohol harder to find (though I have doubts about alcohol, since I grew up in a country where alcohol is on the table every day and somehow we seem to handle alcohol addictions better than other countries with lots of rules and prohibitions). Use smaller serving portions and smaller (but taller) glasses and plates. Marteau et al. even suggest "standing desks" in classrooms to have students spend more calories (this one made me smile).

Here's my two cents. As you know, I grew up in Italy, a country that very much cherishes food and spending social time at the table. I think Italians have pushed things to the far extreme, and now, when I go back to visit, after about one hour of sitting at the table "socializing" I get a little restless. Much of the overweight problems in Italy come from spending too much time at the table. After a while you don't feel hungry anymore but you just keep eating because food is being offered to you.

On the other hand, I see that the United States have the exact opposite problem. There's no definite time of when to eat lunch or dinner, and when you look around you see people eating at any given time of the day. This is just my personal opinion, of course, but I truly believe that introducing fixed eating times in the day can greatly help towards healthier eating behaviors. Also, we should learn from our children. When they are full they stop eating. Parents tend to get edgy and force them to eat more, whereas maybe it should be opposite, it should be the children telling the parents to stop eating so we can all get back into the habit of eating only when we're hungry. Unfortunately, because eating is so much part of our social life and social celebrations, in real life, things tend to get more complicated.

[1] Theresa M. Marteau, Gareth J. Hollands, & Paul C. Fletcher (2012). Changing Human Behavior to Prevent Disease: The Importance of Targeting Automatic Processes Science

Juggling languages and sounds

Growing up my dominant language was Italian. However, thanks to my dad's sabbaticals, on more than one occasions we lived in English-speaking countries for long periods of time. My brain would reset to Italian as soon as we returned, but I never forgot English, and it was definitely easier to transition again when, as an adult, I moved to the US. However, to this day, I have yet to get rid of that feeling of inadequateness that sticks to me in many situations, whether here or back in Italy. You have no idea how many times I've said the wrong thing at the wrong time and, even worse, I had no idea what I'd said but could only guess from the snickers and smirks around me. Well, it turns out, being bilingual is no easy task, but it has its advantages, too.

"With improved juggling ability, novice jugglers demonstrate structural enhancements in a cortical region associated with processing and storage of complex visual motion. Similarly, the bilingual, a mental juggler of two languages, shows structural and functional enhancements in cortical regions involved in language use and executive control, likely resulting from a lifetime of communicating in two languages. [. . .] The need to constantly control two languages confers advantages in the executive system, the system that directs cognitive processing [1]."

"Mental juggler of two languages" . . . I love it, I can totally relate to this metaphor. BTW, I never felt truly bilingual until I started mixing up it's and its, your and you're... !

Krizman et al. [1] reasoned that since musical training enhances cognitive and sensory processing, a similar neural enhancement would be noticed in bilinguals.

"To test this prediction, performance on a task of integrated visual and auditory sustained selective attention was compared between highly-proficient Spanish-English bilinguals and English monolinguals."

The researchers tested differences between bilinguals and monolinguals in the auditory system. I'm not at all surprised that you would find a difference. For example, I've noticed on more than one occasion that because Italian is a phonetic language (words are pronounced as they are written), many Italians who learn English as adults tend to pronounce English words as they'd read them in Italian. To me, this bias introduced by knowing the written word, or better, the inability to pronounce a word unless you see it written, attests to the fact that while growing up a language is a set of sounds one learns to reproduce, once an adult, this ability is somehow lost. Since the sound is per se "unrecognizable," the brain switches to a visual stimulus instead (the written word).

Back to the paper: as specific auditory stimulus, the researchers used the syllable "da" presented in the context of "multitalker babble relative to a quiet acoustic background." The results:

"Bilinguals, relative to monolinguals, showed enhanced sub-cortical representation of the fundamental frequency of the speech sound as well as improved sustained selective attention."

Like music training, language learning impacts subcortical sound processing. The evidence collected by Krizman et al. suggests that because bilinguals constantly juggle sounds between two languages, they possess a neural enhancement in the way sound is encoded in their brains. Like with musicians, the researchers claim, their auditory system is highly efficient, flexible, and better focused in the sound processing.

I just want to add a personal note: we tend to think of language as a way to convey our thoughts, but would we have thoughts at all without a language? I didn't realize how lucky I've been to have learned English in my childhood until, as an adult, I tried to learn German. Languages do shape the way you think, and in order to learn a new language you truly have to change the way you're thinking. I still can't quite grasp the meaning of German dependent clauses until you get to the end of the sentence (a verb!!! please give me a verb!). It feels like one of those super-high stacks where I'm longing for a "pop operation" to happen. . . And once I have a verb I have to stop and reconstruct the sentence. It's not until you learn to think that way that you truly master the language.

I'm fascinated by the intrinsic relationship between thought, consciousness, and language. Feel free to chip in with your thoughts. In English, please. ;-)

Krizman, J., Marian, V., Shook, A., Skoe, E., & Kraus, N. (2012). From the Cover: Subcortical encoding of sound is enhanced in bilinguals and relates to executive function advantages Proceedings of the National Academy of Sciences, 109 (20), 7877-7881 DOI: 10.1073/pnas.1201575109

Have you been blogging lately?

I have to admit I'm obsessed with social networking. I have a love-hate relationship with the whole thing. Until last year I would've sworn I'd never jump the "networking" fence. My thoughts: "There's enough background noise already on the Internet." And: "I've got nothing interesting today."

Whether my posts are background noise or not, I'll leave it to you guys to decide, but I'm myself appalled by the fact that I've been blogging since last July and recently surpassed the threshold of 100 posts. That's not bad for somebody who thought they had nothing to say!

I can't help but wonder, though: what makes social networking so appealing? And how do people behave on the Internet? I've myself been on a couple of boards and found quite different behaviors, ranging from extremely aggressive to extremely supportive (yes, I love my G+ friends, absolutely love you guys!) From what I read about these things, the trend seems to be towards supportive. In fact, websites like Wikipedia and Foldit count on collaborative learning and crowdsourcing through networks based on the assumption that shared knowledge can rise over the background noise and provide meaningful advancements. A new research field has risen in order to analyze the huge amounts of data now available through the Internet.

It's mind boggling, isn't it?

All this to say that, much like I did in this post, I continue to avidly browse the literature looking for more info on social networks. Back when I wrote that post I hypothesized that "likes" on Facebook spread like viruses. My own experiment tells me that's not the case, but guess what? I did find something in the literature that mentions networks and viruses! Check it out:

"The user-generated content showed interesting viral-spreading patterns within blogs. Topical content such as news and political commentary spreads quickly by the hour and then quickly disappears, while non-topical content such as music and entertainment propagates slowly over a much long period of time [1]."

Ha! I knew I was right! Okay, I had the wrong "target." What's viral here is not the "likes" on Facebook, but blog content: for this particular study Cha et al. [1] analyzed 8.7 million posts from 1.1 million blogs -- wow, that's a lot!

Now, while I'm morbidly curious about these things, people smarter than me keep an eye on these data because of their economic value:

"Sentiments embedded in short text updates in social media have been shown to effectively predict and even precede the daily stock price variation (Bollen et al. 2011). Likewise, the blogosphere has been shown effective in capturing up-to-date news (Leskovec et al. 2009). In fact, a non-negligible fraction of news items shared in these social media are known faster than the traditional, authoritative news sources."

The paper lists several findings. First, when hey looked at the network structure of blogs, they saw a heavy-tailed distribution. Apparently, this is common to most network data: when you graph users vs. the amount of use/contribution to the network, you see few individuals contributing a lot (a spike in the graph), then a steep decline and a long tail indicating that the vast majority of the users contributes occasionally. Same with tweets, wikipedia edits, etc. However, unlike most other networks, blogs show much less reciprocity. That's understandable, as blogs are more intended as a means to publish content rather than exchange, giving rise to much less bidirectional nodes when you look at the blog graphs compared to posts on Facebook or Twitter.

The researchers also found that

"media content spreads according to two broad patterns: flash floods and ripples. The first group includes topical content such as news, political commentary, and opinion. Like flash floods, these types of content spread quickly by the hour and then quickly disappear. This demonstrates the role of blogs as a social medium that helps and influences how opinions form and spread on current issues. The second group includes non-topical content such as music and entertainment. Like ripples, old content (produced more than a year ago) can get rediscovered and again start gaining the attention of bloggers, albeit at a slow rate."

[1] Cha, M., Pérez, J., & Haddadi, H. (2011). The spread of media content through blogs Social Network Analysis and Mining DOI: 10.1007/s13278-011-0040-x

Enough with OXTR associations. Here's what I really want to know.

EDIT: After reading the post, please check out the comments. Luke, from Genomes Unzipped, helped me understand the matter better, so don't miss his comment!

Another OXTR paper came out in PNAS, the third since September. OXTR is the gene coding the oxytocin receptor. Given the benefits of oxytocin (dubbed the "love hormone"), people have focused on studying this gene and, in particular, possible associations between a common OXTR polymorphism, rs53576, and various behaviors:

"One SNP in the third intron of OXTR has emerged as a particularly promising candidate in recent studies on human social behavior: rs53576 (G/A). In recent studies, the A allele of rs53576 has been associated with reduced maternal sensitivity to child behavior, lower empathy, reduced reward dependence, lower optimism and self-esteem, and, in men, negative affect. Moreover, the A allele has also been associated with a larger startle response and reduced amygdala activation during emotional face processing. Associations have also been reported between other variants of OXTR and amygdala volume, risk for autism, the quality of infants‚ attachment bonds with their caregivers, attachment anxiety in adult females, and autistic-like social difficulties in adult males [1]."

This study in particular [1] recruited 194 individuals and found an association between the SNP in question and the way the participants reacted to positive feedback during stressful situations. They did this by measuring cortisol responses to stress based on the fact that psychosocial stress increase the levels of salivary cortisol. In AA carriers they found that these levels remained unchanged whether they received the support or not. The researchers conclude:

"Physiologically, it can be speculated that oxytocin released in the context of social support influences stress processing systems via oxytocin receptors in hypothalamic‚ limbic circuits. One likely important site of action is the amygdala, critically involved in basic emotional processing and the regulation of complex social behavior."

I confess I've been eagerly following these OXTR studies and indeed they make a great story. There's a part, though, that puzzles me, and the reason why I'm discussing this paper today is to ask a general question. If you're an expert on these things I welcome your input.

I understand these are important studies because, despite some recent criticism, they are still getting published, and PNAS, as we all know, is one of the top science journals out there. However, the thing I don't understand is that rs53576 is a silent SNP. That's actually not surprising, because, as it turns out, most common polymorphisms are silent. What is surprising, though, is that most silent SNPs are non functional, and none of these studies I've read seems to raise the question. Let me explain.

Rs53576 sits in an intron, a part of the gene that is not transcribed into RNA and hence, in this case, does not affect the way the oxytocin receptor is made. In the analogous studies we do in my group, which are NOT on humans, we look for non-silent mutations because those are the ones that affect the crystal structure of the protein. We then look at what differences in structure these mutations yield to explain how more or less molecules bind to the protein, and this how we explain the observed effects. If rs53576 were a non-silent mutation, I'd know where to look to explain these associations: I'd look at how the SNP affects the crystal structure of the receptor, the hypothesis being that the oxytocin receptor in AA carriers binds less oxytocin than GG carriers (or something along those lines, I obviously don't know the details of this particular receptor). But rs53576 is silent. Hence, if the associations are real, there is something else going on. So, why hasn't anybody raised the question of what else is going on here?

The first thing that comes to mind is that this particular SNP could be in linkage disequilibrium with some other SNP or groups of SNPs which, instead, are non-silent. We tend to inherit polymorphisms in groups, and so if rs53576 comes in the same "package" (they're called haplotype blocks) as some other functional SNP, then rs53576 is NOT the causal SNP for all these effects and we should really be looking elsewhere. The way to find out, of course, is to repeat all these studies with whole genome data. But, it could also be an epigenetic change or a post-transcriptional modification occurring between the primary transcript RNA (which contains both introns and exons) and the mature messenger RNA (which then yields to the protein). The positions of introns can indeed affect the translational properties of the RNA, and that's what yields to the so-called "functional intronic SNPs." The fact that intronic polymorphisms can be functional is extremely interesting, and in fact, last year, this study showed that one particular SNP found in one intron of GH1, the growth hormone, could indeed be functional.

Whatever it is, at this point, isn't it more interesting to investigate what's going on with this SNP at the molecular level rather than looking at all these association studies which may or may not be true?

[1] Chen, F., Kumsta, R., von Dawans, B., Monakhov, M., Ebstein, R., & Heinrichs, M. (2011). Common oxytocin receptor gene (OXTR) polymorphism and social support interact to reduce stress in humans Proceedings of the National Academy of Sciences, 108 (50), 19937-19942 DOI: 10.1073/pnas.1113079108

Photo: Fall colors along the Rio Grande. Shutter speed 1/40, F-stop 5.6, ISO speed 100, and focal length 85mm.

MHC molecules, mating, sniffing, and birthcontrol: believe me, there's a link!

Today we talk about… mating! Whoa -- did you just see that spike in the stats page? Haha, okay, but first you have to sit through the usual genetic lesson. Here it goes: we start talking about the major histocompatibility complex, or MHC.

I've mentioned many times in my previous posts that in order to trigger an immune response you have to make sure that the immune system recognizes the antigen, or "foreign" object. Antigens are made of proteins that, once inside the cell, are chopped into bits and pieces. The bits and pieces are then transported to the cell surface and "presented" to T-lymphocytes, which in turn recognize the bits as a "red flag" (as in, "ALARM! The cell has been infected with foreign and dangerous object!"), and destroy the cell. MHC molecules have the function of grabbing the bits of proteins inside the cell and presenting them to the cell surface. This is a very important step in the immune response, because without this "presentation" the immune system is unable to recognize the antigen.

Now, the genes that code the MHC molecules are highly polymorphic: what this means is that it's a DNA region that varies greatly across individuals. Why? Because the broader range of MHC molecules we have, the better chances to recognize even the rarest antigen that invades our body. Natural selection favors variety in the MHC genes. Having different alleles for these genes is beneficial for disease resistance. Basically, it makes our immune system stronger.

How do we get different alleles? Remember, we inherit one copy of each gene from our mother, and one from our father, and we get discordant alleles when the mother's copy is different from the father's. Studies have shown that mating occurs preferentially between MHC discordant alleles [1]. And how do we detect people with different MHC alleles than ours? By sniffing. Seriously.

This is actually an old study (1995), and many of you may already know about it, but back then the genetics wasn't known, and that's the part I'd like to add here. Anyways, Wedekind et al. [2] enrolled a sample of male and female students. They had the male participants wear the same T-shirt for two consecutive nights, and then they asked the ladies to rate the "odor pleasantness" of six T-shirts, chosen so that three came from MHC-similar males, and three from MHC-dissimilar males. A curious trivia is that the women in the study used nasal sprays to enhance their sense of smell, and they had all read Suskind's novel "The Perfume." Interestingly, the researchers found a correlation between odor preferences and discordant MHC.  

Let's look at the genetics behind the scenes. The genes that regulate olfactory receptors are all over our genome. However, Ehlers et al. [3] found a very large cluster (36 genes) very close to the HLA complex on chromosome 6. This entire region is in strong linkage disequilibrium, which is a very complicated way geneticists use to say that basically we tend to inherit these genes together. You know how chromosomes split before they turn into oocytes or spermatocytes? Well, the splitting is not completely random, and it turns out that these olfactory receptor genes are highly correlated to the HLA genes (they tend to "stick" together), which would explain how odor preferences would correlate to discordant MHC types.

Wow, I've managed to weave a link through the first three items in my schizophrenic title. Now to the fourth one: birth control pills. Well, the Wedekind study found that the correlation varied depending on the women's hormonal status and, furthermore, the trend reversed for women on the pill. In other words, women on the pill seemed to prefer the T-shirts from MHC-similar men.

Okay, all of the above made a fantastic punchline, but… how about the caveats?

For starters, Roberts et al. [4] in 2008 repeated the exact same experiment Wedekind et al. did and, alas, couldn't reproduce the results. What they did find was that single women seemed to prefer the odor from MHC-similar men, while women in a relationship preferred odors form MHC-dissimilar men.

By the time I came to the end of the paper, they had done so many tests that any p-value they found would have to be taken with a grain of salt. And in all fairness, what they propose to measure in these studies are variables extremely hard to quantify. The likeability of a certain odor varies not only from person to person, but from day to day. Have you ever shopped for a fragrance? After spraying a few testers, don't they all smell the same?

As for the biology caveats (and for this part I have to thank my dad!):

1) In mammals sexual stimuli are regulated through pheromones. While generic smells are perceived through the olfactory receptors in the epithelium inside the nasal cavity, pheromones are sensed through the vomeronasal organ. The two are regulated by different genes.

2) In humans the vomeronasal organ has lost its function, mostly because it got replaced by the fact that we can see colors. This has caused a shift: most sexual stimuli in humans are perceived through sight, and the genes regulating the vomeronasal organ have become pseudogenes (non-coding).

3) Lastly, how we react to odors is not simply a genetic behavior, but it is highly correlated to the environment. In fact, it changes throughout our lifetime as we "learn" to like certain smells more than others, and this is due to the way our brain changes and reacts to the environment.

Nonetheless, these are certainly interesting experiments as they point to "trends" in human behavior. They give some insights on how much we are driven by hormonal changes, and on the complex ways physiology and environment weave together into making who we are.

[1] Milinski, M. (2006). The Major Histocompatibility Complex, Sexual Selection, and Mate Choice Annual Review of Ecology, Evolution, and Systematics, 37 (1), 159-186 DOI: 10.1146/annurev.ecolsys.37.091305.110242

[2] Wedekind C, Seebeck T, Bettens F, & Paepke AJ (1995). MHC-dependent mate preferences in humans. Proceedings. Biological sciences / The Royal Society, 260 (1359), 245-9 PMID: 7630893

[3] Ehlers A, Beck S, Forbes SA, Trowsdale J, Volz A, Younger R, & Ziegler A (2000). MHC-linked olfactory receptor loci exhibit polymorphism and contribute to extended HLA/OR-haplotypes. Genome research, 10 (12), 1968-78 PMID: 11116091

[4] Roberts SC, Gosling LM, Carter V, & Petrie M (2008). MHC-correlated odour preferences in humans and the use of oral contraceptives. Proceedings. Biological sciences / The Royal Society, 275 (1652), 2715-22 PMID: 18700206

Facebook and the unselfish gene

So I finally did it. As some of you regulars may have noticed, I put the blog on Facebook. And then I instantly became needy and sent out a bulk of emails begging people to like me. I sent out five and since they're very nice friends of mine, they all liked me. And then I thought, "Well, now, my friends' friends' will like me, and then my friends' friends' friends', and then..."

Hmm. That got me thinking. Does it work like with viruses? No, seriously, do "likes" spread like a viral infection in the body? If not, what kind of network do they resemble? Neurons? Random walks? Traffic network? Surely somebody has thought of modeling this -- does anybody know?

I really got curious about this. I logged onto PubMed and did a search under the keyword "Facebook." I got around 200 hits, none of which answered my questions, but I did find a few papers that captured my attention, so I thought I'd list them below.

• The unselfish gene [1]. Species compete for resources. We've learned in school that natural selection is a competition among the fittest. Philosophers like Hobbes and Machiavelli have stated that humans are essentially selfish, pushing societies to promote self-interest with the use of incentives and punishments. In his review, Dr. Benkler looks at how this line of thinking has changed in the past few years. In fact, we now believe that evolution selects cooperation over competition. The evidence, according to Benkler, doesn't come from evolutionary biology only, but also from sociology, psychology, and economics. And to prove his point, Benkler points to the success of social networks like Facebook, Craigslist, and LinkedIn, which provide emotional, social, and psychological support, gratification, and a great deal of information resources. The sharing of information that goes through the Internet is an indication of cooperation. Indeed, my PubMed search yielded many results on the benefits of Facebook and social networking when it comes to health support groups, health care, and advantages of networking for medical practices. So, I completely agree, except I do find Facebook a little selfish when it comes to... self-promotion. Ahem, yes, I confess I am myself guilty of the crime, since I put my blog in there out of a selfish, egotistical need to have readers...

• Facebook is smoking [2]. This one sounded intriguing. Does the title imply that Facebook is as addictive as smoking? Or that it's as cancerogenic as smoking? Or maybe, Facebook is smoking on your computer after so much use? Unfortunately, I couldn't find anything besides the title, not even the abstract.

• Mirror, mirror on my Facebook wall: effects of exposure to Facebook on self-esteem [3]. Does Facebook enhance or diminish self-esteem? My intuition would be that it requires some solid self-esteem to put yourself "out there." The debate is still very much open, however, some of the literature* seems to indicate that Facebook has beneficial effects on self-esteem. So, stop hiding! Find the guts, go out there, and you'll be a better person! (Yes, yes, I am indeed preaching to myself! Again, guilty.)

* In my literature search, unfortunately, there were numerous papers I didn't have access to.

All of the above is fascinating and interesting, but what about the networking model? I still think a viral infection model might work: you need to re-define parameters such as fitness cost and effective population size. For example, you might send the request to "like you" to, say, 10 friends, but only the ones who will actually click on the like button are the ones who actually "replicate." Say you get 7 likes. Now, all the 7 friends' friends will see the likes, but how many will go ahead and click the like button in turn? That's the effective size population, how many "likes" will actually generate new "likes." In this model there's no immune pressure, but if the effective size is too small, then the infection doesn't take off.

Obviously, this is just my speculations, so I did a second PubMed search and this time I typed "Facebook viral," hoping I'd get some insight on whether Facebook "likes" spread like a virus. This is the only entry I got:

• Using the Internet and social media to promote condom use in Turkey [4]. Not exactly what I meant in my search, but look at the bright side -- another Facebook success story.

That's all for today. Short post, I know, but hey, all those refreshing clicks on FB to check the number of likes, it's a lot of work, you know?

... Pssst. Hey. If you happen to have a spare second, would you click on the like button up there? ...

Okay, those last two statements were jokes. Seriously. Just give me a pat on the back and my self-esteem will thrive. Promise.

[1] Benkler Y (2011). The unselfish gene. Harvard business review, 89 (7-8) PMID: 21800472

[2] Mgweba L, Dlamini S, Kassim J, Planting T, & Smith D (2009). Facebook is smoking. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 99 (11) PMID: 20222194

[3] Gonzales AL, & Hancock JT (2011). Mirror, mirror on my Facebook wall: effects of exposure to Facebook on self-esteem. Cyberpsychology, behavior and social networking, 14 (1-2), 79-83 PMID: 21329447

[4] Purdy CH (2011). Using the Internet and social media to promote condom use in Turkey. Reproductive health matters, 19 (37), 157-65 PMID: 21555096

Photo: last dahlias of the season! Focal length 85mm, F-stop 20, shutter speed 1/50, ISO 100. A special thanks goes to my neighbor who does an amazing job growing these beautiful flowers and then kindly lets me photograph them.

All you need is love... and the right alleles

It's been called the "love hormone" because studies have shown that it is released during labor and breastfeeding. Children soothed by their mothers produce it, and, apparently, it has a role in easing social interactions. Oxytocin is a hormone secreted by the pituitary gland. It is a neurotransmitter, which basically means that it helps send signals from the brain to the receiving cells.

OXTR is the oxytocin gene receptor, in other words, this gene codes the protein that sits on the surface of the cell waiting to "grab" the oxytocin. So, if oxytocin has such beneficial effects on our behavior, it seems natural to look into this gene and see how it affects us, right?

That's exactly what a study published in this week's issue of PNAS [1] did. The researchers (from UCLA, UCSB, and Ohio State University) found one particular SNP in OXTR to be associated with three psychological traits: optimism, self-esteem, and mastery (the ability of making decisions, of being determined to achieve certain outcomes in life). This is an important finding, since the traits they found to be linked with OXTR are known to be correlated with positive health outcomes and good stress management.

Okay, let's back up a little. What's a SNP?

You and I share most of our DNA. We all do. There are very few loci where DNA differs across people, and SNPs are some of those loci. SNP (pronounced "snip") stands for Single Nucleotide Polymorphism, and it represents one particular base in the DNA that's found to be changing across the population (hence the "polyphormism"). It's a single base, but because we have two copies, it is represented by two nucleotides. The SNP found in the PNAS paper, for example, is represented by the following alleles in the population: AA, AG, and GG. In other words, when you look at people's DNA at that particular position, you'll find that some carry a GG, some an AG, and some others an AA. So how was the association found? The researchers recruited a number of subjects and found out which alleles they carried. Then they measured their psychological traits, and they saw that individuals that carried the "A" allele had a tendency to have lower levels of optimism, self-esteem, and mastery, and higher levels of depression.

Now to the caveats.

In general, looking at one SNP only gives a somehow limited picture. Genetics is not just DNA, rather a very complicated hierarchy of interactions, mechanisms, and cascade effects. Genes often interact and "combine" forces. For example, groups of multiple SNPs tend to be inherited together, and "piggy-back" mutations appear as an effect of chromosomal recombination. In this case in particular, this hypothesis seems plausible given the fact that the SNP under investigation is silent, hence does not affect the structure of the protein OXTR encodes. Furthermore, one must keep in mind that certain traits can be altered by epigenetic changes. Caveats aside, it is certainly fascinating to see how genes can affect our behavior and state of mind, and I look forward to the next papers from this group.

[1] Saphire-Bernstein, S., Way, B., Kim, H., Sherman, D., & Taylor, S. (2011). Oxytocin receptor gene (OXTR) is related to psychological resources Proceedings of the National Academy of Sciences, 108 (37), 15118-15122 DOI: 10.1073/pnas.1113137108

Photo: aspens at sunset. Canon 40D, focal length 81mm, F-stop 5.6, shutter speed 1/100. On a side note, those three aspens came down this summer. Too much wind, sadly.

The neuroscience of politics

Fascinating article over at DISCOVER Magazine: Your Brain on Politics: The Cognitive Neuroscience of Liberals and Conservatives, by Andrea Kuszewski. Very well written and mindful of all the caveats.

Photo: dawn. Shutter speed 1/160, focal length 70mm, ISO 100, F-stop 5.6. I know, I keep photographing the same trees. It's because if I photograph them often enough, God will give them to me. Just kidding. Click on the link to see whom I'm paraphrasing.

Wanna be likeable? Zip your mouth!

I saw this post on BPS Research Digest: Prolific gossipers are disliked and seen as weak and couldn't help but spread the word. This is the original paper:

Is gossip power? The inverse relationships between gossip, power, and likability

The paper, by Sally Farley, from the University of Baltimore, looked at 128 individuals who were asked to rate how likeable (or not) people they knew as either gossipers or non-gossipers were.

It appears that gossiping "ain't so cool" after all.

Although, the statistician in me has me wondering: "What about bias?" Whenever people fill out questionnaires like this one, how can researchers ensure that they will answer truthfully? Especially in a study like this, where we all know that "morally" gossiping is bad, is the likelihood of a "moral bias" (as in people tend to answer that gossiping makes one less likeable because they know that's what they are supposed to think) real?

Photo: fall leaves. Canon 40D, exposure time 1/60, focal length 85mm. 

Intelligent people live longer... really?

I came across this abstract from a 2008 Nature essay:

Why do intelligent people live longer? 

We must discover why cognitive differences are related to morbidity and mortality in order to help tackle health inequalities.

The statistics show that children with high IQs tend to live longer than those with less intelligence. What the statistics don't tell us is why. What thing or things do intelligent people do that can delay mortality? Ian Deary explains how cognitive epidemiologists are trying to answer the question, and potentially contribute to the redistribution of health.

Prof. Deary is the director of the Centre for Cognitive Epidemiology of the University of Edinburgh. I never met him, but I looked up his research and what he does, and it is certainly impressive. The essay looks at a number of retrospective studies where the IQ was measured earlier in life, and the longevity of the subjects was measured. The article goes on trying to give possible explanations in order to, like the abstract says, "help tackle health inequalities."

The title seemed provocative enough to spark some discussion, so I thought I'd start by giving my two cents. I won't get into the whole issue of "how do we measure intelligence," as that is not my field (though I'd love to hear from experts). Instead, I tried to read the paper from a purely statistical point of view. And this is the part that got me puzzled:

"First, what occurs to many people as an obvious pathway of explanation, is that intelligence is associated with more education, and thereafter with more professional occupations that might place the person in healthier environments. Statistical adjustment for education and adult social class can make the association between early-life intelligence and mortality lessen or disappear."

You see, to a statistician that statement settles the argument. If correcting for education and social class makes the association disappear, then the association is spurious. Instead, the Nature essay deems it an "over-adjustment."

Whenever you are trying to fit a statistical model you have to make sure that your independent variables are truly independent. Example: suppose I take a population of ten Asians and ten Caucasians, follow them for forty years, and learn that after forty years all Caucasians are dead and all Asians are still alive. I might naively conclude that Asians live longer than Caucasians. Now suppose I tell you that eight out of ten Caucasians were smokers. Well, smoke turns out to be what statisticians call a confounding factor, in other words, a variable that's correlated to both the dependent and the independent variables. Not including it in the analysis leads to spurious relationships. In my made-up example, if I stratify my analysis between smokers and non-smokers and repeat the statistical test, this time I will find no significant difference in the longevity of Caucasians versus that of Asians.

In the case of intelligence and longevity, "income/social class" is an obvious confounding factor. We all know that a healthy lifestyle is expensive. A diet high in vitamins and fibers, the time to exercise, medications, regular medical check-ups: sadly, in today's world, they are all privileges for the well-off. Furthermore, the earlier you make healthy lifestyle choices, the better your odds later in life. So, income at birth also weighs in: children born in poor environments may not have access to vaccinations, medications, healthy foods, and other more general healthy lifestyle choices, all things that will affect them as adults. I may be missing something crucial, but it really doesn't seem like an over-adjustment to me.

In a way, we're saying the same thing. There is an association. But: is the association causal or is it masking an underlying, stronger association? The essay seems to suggest that the association is indeed indicative of something else, but somehow it leaves the question open-ended, concluding: "The things that people with higher intelligence have and do that makes them live longer may be found and, we hope, shared, towards the goal of better and more equal health."

Still, I would really like to see a similar study with education and social class folded in. Because if it turns out that the true underlying drive for a better and longer life is income, well, in that case I do have a suggestion to answer the above question: let's make health care and healthy life styles more affordable to people.

Picture: Colors at the Pike Place Market, Seattle. Canon 40D, focal length 70mm, exposure time 1/40.