Serotonin-deprived mice may be gay (or not)

A couple of days back I posted a link to Ed Yong’s synopsis of the paper just released by Nature purporting to show that modulating serotonin levels in mice could have an effect on their sexual orientation. In short, low- or no-serotonin producing mice no longer discriminated sexually between males and females, mounting cagemates of either gender with equal vigor. There’s really no point in re-summarizing the study as Scicurious has provided an excellent recap.

Here’s a serotonin deficient mouse mounting first a male, then a female:

As the paper’s authors themselves noted, one alternative explanation for the findings is that the loss of gender discrimination was a byproduct of a serotonin-regulated increase in sexual behavior rather then a change in sexual preference per se. Although the study showed that no serotonin mice didn’t show increased sexual behavior towards solo females, they mounted close to 90% of the females in that condition, not leaving a lot of room to show an increase.

Furthermore, mice rely on pheromones to determine who is female and who’s not. The depletion of serotonin might have had some effect on the peripheral olfactory system such that the mice couldn’t distinguish the males from the females. The study did include a control condition which showed mice’s olfactory systems were still at least somewhat functional (they could distinguish between sesame oil and air, and could still identify fox urine.) But maybe the difference between physiological levels of pheromone requires a level of sensitivity in the olfactory system that was lost in the serotonin-depleted animals. I’m not convinced that this explanation has been sufficiently ruled out.

Finally, on a more speculative note, serotonin is known to play a large role in regulating forms of social behavior including aggressiveness and social dominance, in a wide range of species from mice to humans. These animals were completely depleted of serotonin which should lead to significant changes in their social behavior. Past research has associated low serotonin with increased aggressiveness in mammals. Could it be that when male mice mount other males, they are doing something other than “getting it on”? (Male mice with normal levels of serotonin sometimes do mount male mice. Why’s that?).

Although the study’s findings are just the kind of topic that the mainstream media loves (anything involving sex), and they’ve responded with salacious headlines in kind, it seems prudent to interpret the results cautiously and await further work.

worthy links: Rama, acupuncture, disgust and politics (redux), mouse sex

V.S. Ramachandran gives a stimulating TED lecture and a short interview, mostly about mirror neurons, over at Neurophilosophy.

NeuroLogica’s Steven Novella recaps a recent study showing that acupuncture doesn’t work — and points out the clever way in which the failure was spun by the study’s authors.

Just the other day, I summarized a recent study looking at the relationship between disgust/purity and political ideology. In this short video, a brief discourse by Yale’s Paul Bloom on the topic.

Over at Not Exactly Rocket Science, Ed Wong talks about work out of Bejing that showed male mice with reduced serotonin levels became less choosy about the sex of their sexual partners. And as should be expected, the sensationalistic headlines from mass media organizations shortly followed. From the BBC: “Sexual preference chemical found” And from CBS News, a NY Post-worthy headline: “Serotonin sex bomb: How to make a mouse bisexual or just really horny”

worthy links

Nice piece from the Boston Globe on the positive benefits of solitude. (My friend Adam Waytz, from the Harvard psychology department, gets a mention.)

Congenitally blind people use visual cortex to do language processing

An essay by June Carbone regards the role of neuroscience in determining punishment for adolescents who commit crimes such as murder. Focused on a recent US Supreme Court decision on the juvenile death penalty, the piece points out some of the limitations of applying neuroscientific findings to issues of jurisprudence.

A new study from researchers at Northeastern University says day traders make more money when they stay with the herd.

The Seductive Allure of Uncertainty

Amongst the forests of trees cut down in support of self-help books on dating, some not inconsequential percentage of lumber has probably been exclusively dedicated to variants on the theme that one must “play hard to get” to find love. If you never heard this expression, I would be curious to know what solar system you’ve just arrived from. And for you, my alien friend, I say welcome to our planet, and please allow me to explain. As it’s been passed down through the ages, the story goes that If a person wants to attract the interest of another toward whom they have romantic inclinations, they should be aloof and slightly stand-offish, so as to gain the attention and interest of their betrothed. Popular self-help manifestos such as “Why men love bitches,” are based on the idea of making oneself more attractive by decreasing one’s availability (to put it mildly). Going back several hundred years, even Juliet, from Shakespeare’s most famous play, knew as much when she told Romeo that “…if you think it’s too easy and quick to win my heart, I’ll frown and play hard-to-get, as long as that will make you try to win me.” I remember hearing some variant on this theme (“Don’t be too eager”) from older boys when I was a scrawny young fellow just becoming interested in girls for the first time.

Erin Whitchurch and colleagues from Harvard University were interested in how this seeming truism (the Uncertainty Principle), conflicted with another observation from the social psychological literature, which is that people tend to like those who like them back (known as the Reciprocity Principle). Interested in testing this principles against each other, they designed a study whereby 47 women viewed Facebook profiles of a set of men who, they were told, had previously viewed their profiles and rated how much “they would get along with each woman if they got to know her better.” A subject knew that a given man either liked her a lot, liked her about average or they were uncertain as to whether the man liked her or not. Then she would rate each man on a number of different dimensions including how much they might like him as “a potential boyfriend” and how much they would be interested in “hooking up” with him.

The results showed that women liked men who liked them a lot more than men who liked them a little, supporting the Reciprocity Principle; that is, we like those who like us back. But the study also supported the Uncertainty Principle (that we like those who we are uncertain about) by showing that women liked men about whose feelings they were uncertain more than men who said they liked them a lot. They also reported thinking a lot more about these men. The authors mention that although this advice has often appeared in the popular press, social psychological research has never confirmed it. The authors also point out important constraints and limitations that bear on the ecological validity of the effect. Among these are the fact that participants didn’t know anything about the men and it’s not clear that this effect would hold after meeting someone and/or beginning a relationship. Perhaps, as they suggest, this finding would be most applicable in the context of online dating, in which people don’t know very much about the other person initially. Also, only females participated and there may be gender differences.

One important point to reiterate is that participants mentioned thinking about the men in the “uncertain” condition much more than in the other conditions. Although I’m not overly familiar with research on dating, romantic attraction, relationships, etc., the reason I was inspired to write about this study is because I’m quite interested in the effect of uncertainty on cognitive and attentional processes and decision making, topics that a handful of recent studies have addressed. One 2010 study from researchers at Cornell found that people were more distracted by hearing one person on a cell phone nearby vs. two people having a conversation, the suggestion being that it was the unpredictable nature of the one-sided conversation that led to participants’ increased distraction. Zachary Tormala at Stanford has performed studies in which he has found that expert advice expressed with low certainty can be more persuasive than that expressed with high certainty. Tormala says that when an expert, say a restaurant critic, is unsure of themselves in a review of a restaurant, this is surprising to people. And “…surprise increases readers’ interest in and involvement with the review, which is essentially a persuasive message, and this promotes persuasion,” says Tormala. “Experts … get more attention and can have more impact when they express uncertainty.” In standard human fear conditioning experiments, the strongest fear conditioning is generally achieved when you shock participants only about a third of the time. That is, the strongest fear responses are generated when participants are maximally uncertain as to when they’re going to be shocked. That’s when you’ve really got their attention.

So, over a variety of different domains and outcomes, uncertainty is the variable common to all of the above situations. From an adaptive perspective it makes sense that we would direct extra attention to unsolved vs. solved problems. As organisms whose very survival is dependent upon our ability to learn about the world around us, we often have no choice but to devote an inordinate amount of attentional energy to the unknown. But from a mechanistic point of view, what motivates this orientation?

There is a rather large scientific literature discussing the role of reward signals in learning and uncertainty. And while its well-established that learning is largely dependent on reward systems, primarily the dopamine system, it’s also been shown that uncertainty alone is subserved by the same system. Going back to the study at hand, it doesn’t seem outrageous to imagine that participants had conflated the reward signal associated with uncertainty about being liked with the reward signal associated with liking someone.
This wouldn’t be surprising as the same dopamine neurons that preferentially report subjectively pleasant events also seem to signal attention-inducing ones. Dopamine neurons fire much more strongly to unexpected rewards and they may also fire strongly when presented even with the prospect of such a possibility, a kind of second-order reward effect. So, the effect could be framed as a kind of neural parlor trick, a technique whereby one can hijack the reward system of another person, causing that person to experience feelings that they then misinterpret.

I’m concerned with how science is presented to the public and how misunderstood scientific findings often become cultural “memes” that permeate the culture and plant incorrect ideas about human nature inside of people’s heads. Whitchurch’s study has already generated just these kind of sensationalistic and over-simplified headlines:


Men should play hard to get, find psychologists

It’s important to keep in mind that the more rewarding your dream girl or guy finds uncertainty, the more likely it is that this “technique” will work on them. And there is evidence that individuals vary in how sensitive they are to uncertainty, so this may not work on everyone. Furthermore, if their attraction to you is driven largely by uncertainty, then what’s going to happen once the uncertainty is no longer there?

(a page from an imagined self-help book):

“You shouldn’t play hard to get. Why? Because, as Harvard researchers have pointed out, it will attract (wo)men to you, but it’s an illusion. They might not be attracted to you because they like you, but because you’ve increased their attention to you through manipulating uncertainty as to how you feel about them! While this might work for as long as you maintain that uncertainty, remember this is not the same thing as someone liking or loving you. While human beings might be wired to pursue certain situations and people because of this, if you’re a healthy, well-adjusted person, you don’t want that kind of person in your life, because they’ll always be interested in chasing the unknown and once they’ve “figured you out,” they’ll be on to the next mystery.”

Love in the time of oxytocin research

Often referred to as the “love drug” or “love hormone”, oxytocin has attracted increasing interest from researchers in recent years. It was originally shown to modulate aspects of social attachment and pair bonding in animals such as the female prairie vole, whose monogamous nature is dependent on oxytocin. Recent research in humans has shown that oxytocin increases trust behavior in economic exchanges and increases perception of trustworthiness in human faces, as well as promoting emotion recognition and altruism. This evidence inspired hopes among some, particularly in the mainstream media, that science might have found a possible pharmacological target for humans who show deficits in prosocial behavior.

But recent evidence has complicated the narrative a bit.

Research has shown that oxytocin plays a role in increased emotional reactivity to both positive and negative social cues. For example, one study from 2009 (Shamay-Tsoory et al) had participants engage in a game of chance with another player (the actor). In one condition, the actor was made to win more than the participant, evoking feelings of envy in the participant. In another condition, the actor was made to lose more than the participant, evoking feelings of “schaudenfrude” or gloating. Participants who were administered oxytocin before playing showed increases in both envy and schaudenfrude (if oxytocin was involved only in enhancing prosocial behavior, we would expect to see the opposite result.) Other research has shown oxytocin increased approach behavior or affiliative drive rather than regulating positive or negative responding per se. And one recent study showed that oxycotin led humans to self-sacrifice for their own group while showing increased aggression toward out-group members. The gist of this set of findings is that oxytocin doesn’t seem to bias individuals toward the positive, but rather can magnify whatever “stimuli” happens to be in someone’s attentional spotlight, be it bad or good, thereby generating an increase in corresponding positive or negative emotional responses.

Jennifer Bartz and colleagues (2010) were curious to explore whether oxytocin could “correct” deficits in pro-social behavior in individuals with borderline personality disorder (BPD), a population famous for emotional instability, extreme impulsive behavior and identity confusion. People with BPD tend to be involved in intense, emotionally volatile relationships characterized by frequent arguing, repeated breakups and extreme aggression. This behavior often extends beyond their romantic relationships, as BPD individuals have also been shown to have difficulty cooperating with strangers. The existing body of research, Bartz et al suggested, offers up contrary predictions. On the one hand, oxytocin could be helpful in reducing the negative behaviors normally associated with BPD in favor of kinder, gentler behavior towards others. Alternatively, oxytocin might have increasingly negative effects for people with BPD, who are chronically concerned with (lack of) trust and abandonment and have difficulty cooperating with others. They’re essentially fixed in a constitutively negative state when it comes to social interactions and increased oxytocin could decrease prosocial behavior even further. Additionally (or alternatively), the oxytocin system might be dysregulated in BPD and could produce different responses (vs. control) to oxytocin as a result.

Bartz and company designed an experiment in which the participant was paired with a partner (in reality, a virtual “computer” partner) to engage in an economic game. In this game, the participant was to make one of two choices that involved financial rewards. The catch was that the amount of the reward was also dependent upon the choice that their “partner” made.

Both players clearly make the most money if they both choose strategy A. But because the player has to make the choice before the partner, the decision involves an element of trust (if your partner defects, you get nothing. If your partner trusts you and you defect, you get $4 and she gets nothing.)

So, what did they find?

Results showed the following:

1. BPD people trusted their partners in an economic game less after they received oxycotin than when they received a placebo.
2. Additionally, when asked if they would be more likely to make a hypothetical decision that would punish their partner, even when they knew their partner had extended trust toward them, they were more likely to punish after Oxytocin than placebo.

Administration of oxytocin to BPD individuals actually decreased pro-social behavior (and increased antisocial behavior). As the experimenters suggest, increasing the salience of a social cue that makes trust issues salient may have caused BPD participants to rely on their normal strategy for trust-dependent social interactions; that is, defect and punish the partner. Or it might have motivated approach/affiliative behaviors which triggered memory of past experiences gone awry and set off chronic and ever-present concerns about trust and rejection (e.g. “reject and punish them before they can do the same to me.”). Finally, the experimenters suggest the possibility that the oxytocin system itself may be dysregulated.

In short, the evidence doesn’t offer overwhelming support for the notion that exogenously-administered oxytocin will be a useful clinical treatment for people with pro-social deficits, such as those with BPD. Additionally, it’s difficult to imagine long-term benefits of oxytocin given that it’s half life when administered intranasally is only about three minutes. It’s been said that the most of the real action with regards to oxytocin is on the receptor end.

Bartz, J., Simeon, D., Hamilton, H., Kim, S. Crystal, S., Braun, A., Vincens, V., & Hollander, E. Oxytocin can hinder trust and cooperation in borderline personality disorder. (2010). Social Cognitive & Affective Neuroscience

Shamay-Tsoory SG, Fischer M, Dvash J, Harari H, Perach-Bloom N, Levkovitz Y (November 2009). “Intranasal administration of oxytocin increases envy and schadenfreude (gloating)”. Biological Psychiatry 66 (9): 864–70.