Tag Archives: humans

Human Oxytocin Research Gets a Drubbing

There’s a new paper out by Gareth Leng and Mike Ludwig1 that bears the coy title “Intranasal Oxytocin: Myths and Delusions” (get the full text here before it disappears behind a pay wall) that you need to know about if you’re interested in research on the links between oxytocin and human behavior (as I am; see my previous blog entries here, here, and here). Allow me to summarize some highlights, peppered with some of my own (I hope not intemperate) inferences. Caution: There be numbers below, and some back-of-the-envelope arithmetic. If you want to avoid all that, just go to the final paragraph where I quote directly from Gareth and Mike’s summary.

brain-OTFig 1. It’s complicated.

  1. In the brain, it’s the hypothalamus that makes OT, but it’s the pituitary that stores and distributes it to the periphery. I think those two facts are pretty commonly known, but here’s a fact I didn’t know: At any given point in time, the human pituitary gland contains about 14 International Units (IU) of OT (which is about 28 micrograms). So when you read that a researcher has administered 18 or 24IU of oxytocin intranasally as part of a behavioral experiment, bear in mind that they have dumped more than an entire pituitary gland’s worth of OT into the body.
  2. To me, that seems like a lot of extra OT to be floating around out there without us knowing completely what its unintended effects might be. Most scientists who conduct behavioral work on OT with humans think and of course hope that this big payload of OT is benign, and to be clear, I know of no evidence that it is not benign. Even so, research on the use of OT for labor augmentation has found that labor can be stimulated with as little as 3.2 IU of intranasal OT during childbirth by virtue of its effects on the uterus. This is saying a lot about OT’s potential to influence the body’s peripheral tissues because that OT has to overcome the very high levels of oxytocinase (the enzyme that breaks up OT) that circulate during pregnancy. It of course bears repeating that behavioral scientists typically use 24 IU to study behavior, and 24 > 3.2.2
  3. Three decades ago, researchers found that rats that received injections of radiolabeled OT showed some uptake of the OT into regions of the brain that did not have much of a blood brain barrier, but in regions of the brain that did have a decent blood brain barrier, the concentrations were 30 times lower. Furthermore, there was no OT penetration deeper into the brain. Other researchers who have injected rats with subcutaneous doses of OT have managed to increase the rats’ plasma concentrations of OT to 500 times their baseline levels, but they found only threefold increases in the CSF levels. On the basis of these results and others, Leng and Ludwig speculate that as little as 0.002% of the peripherally administered OT is finding its way into the central nervous system, and it has not been proven that any of it is capable of reaching deep brain areas.
  4. The fact that very low levels of OT appear to make it into the central nervous system isn’t a problem in and of itself—if that OT reaches behaviorally interesting brain targets in concentrations that are high enough to produce behavioral effects. However, OT receptors in the brain are generally exposed to much higher levels of OT than are receptors in the periphery (where baseline levels generally range from 0 to 10 pg/ml). As a result, OT receptors in the brain need to be exposed to comparatively high amounts of OT to produce behavioral effects—sometimes as much as 5 to 100 nanograms.
  5. Can an intranasal dose of 24 IU deliver 5 – 100 nanograms of OT to behaviorally relevant brain areas? We can do a little arithmetic to arrive at a guess. The 24 IU that researchers use in intranasal administration studies on humans is equivalent to 48 micrograms, or 48,000 nanograms. Let’s assume (given Point 3 above) that only .002 percent of those 48,000 nanograms is going to get into the brain. If that assumption is OK, then we might expect that brain areas with lots of OT receptors could—as an upper limit—end up with no more than 48,000 nanograms * .00002 = .96 (~1) nanogram of OT. But if 5 – 100 nanograms is what’s needed to produce a behavioral effect, then it seems sensible to conclude that even a 24 IU bolus of OT (which, we must remember, is more than a pituitary gland’s worth of OT) administered peripherally is likely too little to produce enough brain activity to produce a behavioral change—assuming that it’s even able to get into deep brain regions.

Leng and Ludwig aren’t completely closed to the idea that intranasal oxytocin affects behavior via its effects on behaviorally relevant parts of the brain that use oxytocin, but they maintain a cautious stance. I can find no better way to summarize their position clearly than by quoting from their abstract:

The wish to believe in the effectiveness of intranasal oxytocin appears to be widespread, and needs to be guarded against with scepticism and rigor.

1If you don’t know who Gareth Leng and Mike Ludwig are, by the way, and are wondering whether their judgment is backed up by real expertise, by all means have a look at their bona fides.

2A little bet-hedging: I think I read somewhere that there is upregulated gene expression for oxytocin receptors late in pregnancy, so this could explain the uterus’s heightened sensitivity to OT toward the end of pregnancy. Thus, it could be that the uterus becomes so sensitive to OT not because 3.2 IU is “a lot of OT” in any absolute sense, but because the uterus is going out of its way to “sense” it. Either way, 3.2 IU is clearly a detectible amount to any tissue that really “wants”* to detect it.

*If you’re having a hard time with my use of agentic language to refer to the uterus, give this a scan.


Why Do Honor Killings Defy the First Law of Homicide? And Will Smaller Families Lead to Fewer Of Them?

Few categories of human rights violations more deeply scandalize the liberal (with a little-L) moral sensibility than honor killings do. Reliable numbers are hard to come by, but by most credible accounts it seems likely that several thousand Muslim women each year (and more than a few men) are stoned, burned, hanged, strangled, beheaded, stabbed, or shot to death for the sins of getting raped, falling in love, or dressing immodestly. But to anyone who thinks about human behavior from an evolutionary point of view, honor killings are not just morally outrageous: They’re also really puzzling.

As Martin Daly and Margo Wilson documented in their marvelous book Homicide, killers are very rarely the genetic relatives of their victims. Instead, they’re most often strangers, or rivals, or cuckolded lovers (who, of course, are not each others’ kin even if married—at least, not in the sense that matters to natural selection). Indeed, the typically low level of kinship between the victims of homicides and the people who kill them is so predictable that we could get away with calling it “The First Law of Homicide.” When two genetic relatives are involved in a homicide, it’s usually either as co-victims or co-perpetrators, not as victim and perpetrator.

In a sense, a general reluctance to harm or kill one’s genetic relatives is not exactly breaking news. We’ve understood since William Hamilton’s 1963 and 1964 papers that natural selection creates organisms that appear designed to maximize their inclusive fitness (which incorporates the reproductive success of the individual in whom the gene is physically located, as well as the reproductive success of other individuals who are carrying copies of that gene around) rather than their simple direct fitness. Genes “want” to maximize the total number of copies of themselves that are floating around in the world, even if some of those copies are located in other individuals’ gonads. The principle of kin selection virtually guarantees that we’re walking around with instincts that restrain us from harming our relatives, even when they’ve irritated us. To be clear, I’m not saying people never kill their kin (mental illness is a real wild card here), but the fitness disincentives of doing so were so high as our psychology was evolving that the perceived incentives to do so now have to be very high indeed.

Which is what makes honor killings so puzzling. In a recent article, Andrzej Kulczycki and Sarah Windle summarized data on the circumstances behind more than 300 honor killings across Northern Africa and the Middle East. What jumps off the page when you look at their data is how flagrantly honor killings flout the First Law of Homicide: About three-quarters of honor killings are carried out by family members of the victim. To be specific, the victims’ brothers carry out 29% of them, fathers and (to a much lesser extent, mothers), carry out about 25%, and “other male relatives” carry out an additional 19% of them. (Of the remaining 25%, virtually all are carried out by the victims’ husbands/ex-husbands.)

I’m really interested in that 75% that violate the First Law of Homicide. For the perpetrators of honor killings to over-ride their intuitive aversions to killing their own daughters or sisters, the perceived costs of “dishonor” must be very high indeed. We can’t precisely measure the exact fitness value of honor for someone who lives in a so-called culture of honor, of course, but the link between fitness and honor is undeniable. If you live in an honor culture, your honor determines your (and your children’s) job prospects, marriage prospects, ability to recruit help from neighbors, ability to secure a loan, and protection against those who would otherwise do you harm. Honor is an insurance policy, a social security check, and a glowing letter of recommendation rolled into one bundle. The fitness costs of tarnished honor in an honor culture can be steep.

One of the things I came to appreciate about honor while doing research for one of my books is that honor is a sacred commodity. It doesn’t follow the laws we expect actual physical stuff to obey, or the normal laws of economics, or even the normal rules that govern our everyday psychology. It follows the laws of Sacred Things. If you feel sad one day, you can be pretty sure that the feeling won’t last forever. Dishonor doesn’t work like that. Dishonor doesn’t wash off or fade away with time. Dishonor has to be purged or atoned for. More importantly for my argument here, dishonor does not dilute. The dishonor that a “dishonorable” behavior creates for a family is not like a fixed quantity of scarlet paint that can be used to make only a finite number of scarlet letters. When a young woman “dishonors” her family, there’s enough dishonor to thoroughly cover every one of her brothers and sisters, no matter how many brothers and sisters she has.

There’s an interesting prediction waiting in the wings. If I’m right that dishonor does not dilute, then the perceived fitness-associated costs of a single act of dishonor will be larger for a father and mother with many children than for a father and mother with only with only a few children. This has implications for reducing honor killings. Let me illustrate with a thought experiment.

The Costs of Dishonor to a Father Are Higher in Large Families

Say I am a father with nine children and one of my daughters has done something (or, more likely, has had something done to her) that has brought dishonor upon herself and each of her eight siblings. (Believe me, I am more appalled by having to write sentences like these than you are by having to read them, but I can’t come up with a better way to think through these issues than to try to step into the shoes of someone who is actually factoring honor-related concerns into their social decision-making). As the father of these nine children, the dishonored daughter has reduced my fitness by 9d because each of my children will suffer an honor-related fitness cost of d. (It might be better to quantify the hit to my fitness as 9 * .5 = 4.5 because my genetic relatedness to my children with respect to a rare allele that I possess is 0.5 rather than 1.0, but that won’t change anything in what’s to come. Can we please agree to work with 9 so as to make the math prettier?) So, if I am a father of nine children, and I can restore my family’s honor by murdering my dishonored daughter, I can recover 8d units of fitness (by restoring the damaged honor of my other eight children), and it costs me (I know, the thought sickens me as well) the fitness decrement I suffer through murdering one of my offspring.

If, on the other hand, I have only two children, then the perceived fitness cost of my daughter’s dishonor is 2d (a cost of d is imputed to both of my children), and I’d only be able to recover 1d unit of fitness (for my remaining, unmurdered child) by murdering the dishonored daughter. So, for a father with only two children, the calculus is not so clear: Am I better off in the long run to have two children whose honor is tarnished, or only one child whose honor is restored? For any plausible value of d, it’s hard to imagine that the decision-making scales would tilt in favor of killing the dishonored daughter if doing so would leave you with only one child. I’m betting that the father of two will stay his hand under circumstances in which the father of nine might not.

If I’m right about this, then a demographic shift toward smaller families in developing societies could eventually help to solve the problem of honor killings. I couldn’t find any direct evidence to support this prediction, but Manuel Eisner and Lana Ghuneim recently published a study in which they surveyed 856 Jordanian adolescents from 14 different schools to examine the predictors of their attitudes toward honor killings. They found that even when they controlled for the students’ sex (male vs. female), their religion (Muslim vs. non-Muslim), whether their mothers worked outside of the home (a good proxy for modernization), and the parents’ educational levels (also a good proxy for modern thinking), children with four or more siblings had more favorable attitudes toward honor killings than did children with three or fewer siblings. Not an exact test of my prediction, but to the extent that kids adopt their parents’ views, it seems to me that these results are at least tantalizingly consistent.

Do the human rights groups that want to reduce honor killings and other kinds of honor-related violence around the world ever talk about family size as a truly exogenous (and, in principle, modifiable) cause of honor killings? People are pinning their hopes for solving so many other problems around the world on reductions in family size, so perhaps I’m not being too pie-in-the-sky to add “reductions in honor-related violence” to that list of “Ways In Which We’d Be Better Off If People Had Fewer Kids.” As families shrink, I’m guessing that spared lives become subjectively more valuable than restored family honor.