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Who do we think we are? The brain and gender identity January 24, 2010

Posted by Geekgirl in anatomy, brain, Gender Identity, transsexual.

About two years old but still an interesting commentary. Please forgive the term disorder when the author refers to gender identity. This is common in the scientific literature. Thankfully, this year the American Psychological Association has put up for debate changing this terminology.

Brain (2008), 131, 3115-3117


Who do we think we are? The brain and gender identity

No-one, wrote Frank Beach, a notable contributor to the experimental study of hormones and sexual behaviour, ever died from lack of sex. But the personal, social and legal aspects of sexual behaviour are a pervasive pre-occupation in all humans. The variety and vagaries of sex can have severe implications, and the existence of homosexuality and disorders of gender identity demand some sort of explanation(Bancroft, 2008). Neuroscience can ask itself, therefore, why it has contributed so little to understanding human sexuality. One reason is our overall ignorance about the brain, which hinders attempts to relate particular patterns of brain activity to an observable behaviour in a way that contributes to understanding. Another is the effect of sexual mores on the study of sexuality itself: studying sex is still considered a slightly risque´ career, and made difficult by the politics, constraints and prejudices of human societies. It took the AIDS epidemic to convince many governments and funding bodies that studying sex was important and respectable. Most of our information on the neurobiologyof sex comes from animal studies (Becker et al., 2005), but nearly all of what we know about variations in human sexuality, including hetero- and homo-sexuality, and disorders of gender identity (transsexualism), comes from clinical material, anecdotes or even fiction (the three overlap).It is now well-known that sex-determination is heavily reliant upon the sry gene encoded on the Y chromosome. But genes, of course, do nothing themselves: they activate molecules that are the mechanisms, and prominent amongst these is testosterone. During development, the male fetus secretes testosterone—and production maycontinue into early post-natal life. This has dramatic effects on the internal reproductive organs, promoting the masculine arrangement.

But, here we are more interested in what it does to the brain. Experimental studies show that both patterns of sexual behaviour and preference for females are directed towards the ‘male’ type by exposure to testosterone during this critical period (reviewed in Pardridge et al.1982; Gorski, 2002). Whether this applies in all its detail to humans is still debated (Swaab, 2007). Even amongst closely related species, reproductive strategies (particularly female) are curiously varied, which makes extrapolations to humans a risky business (Baum, 2006). Nevertheless, there are experimental grounds for suggesting that variations in prenatal exposure to testosterone may influence later sexual preference (orientation) in man.

But on an equally important issue, that of gender identity (whether we think of ourselves as male or female), the experimental literature is silent. For good reason: animals cannot report, as humans can, on their gender identity, and no-one has found an indirect way to reveal the gender identity of a monkey, let alone a rat. There are no experimental models of  transsexuality. So, studies on the neuroscience of human transsexuality are limited to man alone. The logic behind them is simple, though necessarilylimited. Define a sex difference in some feature of the brain, preferably one known to be associated with sexual behaviour; then show that this difference is in the expected direction in those reporting gender dysphoria (the belief that one’s ‘true’ or ‘core’ gender identity is the opposite of both chromosomal sex and bodily habitus). Since manygender dysphorics are either given or self-administersteroids more typical of the opposite sex, it is important to exclude these as a determinant of the atypical neural feature. A clear association between the neural and behavioural phenotypes suggests that this is causal.

This is, essentially, what Garcia-Falgueras and Swaab report in the current issue (page 3132). The medial preoptic area of the hypothalamus (MPOA) is known to be involved in masculine patterns of sexual behaviour in rodents and monkeys, and to be sexually dimorphic, though, it should be pointed out, there are suggestions that it promotes sexual performance (the ability to copulate) more than motivation for masculine-type sex (reviewed in Balthazart and Ball, 2007). Garcia-Falgueras and Swaab find that partof this area, INAH3 in humans, is larger and has a greater number and density of neurons in males than females, and that male-to-female transsexuals (MtF) resemble females.

But these overall statistics tell only part of the story. Their data show considerable overlap between males, females and MtF. So, either the precision of their methods is not very high, or there is an indistinct relation between INAH3 and individual gender identity. This is odd: people usually have no doubt about their gender, though there are degrees of self-regarded ‘masculinity’ and ‘femininity’. There are other questions: why should more neurons inINAH3 predispose to male sexual identity? It seems unlikely that such simple methods will ever tell us much about the neural basis of human sexuality. The difficulty of interpreting measures such as volume is brought into focus by their first result: they report that brain weight is greater in males than females (not surprising), but that MtF subjects have intermediate values. What are we to make of this?And why are similar differences in INAH3 in previous studies, with male homosexuality (Le Vay,1991)?

Gender identity does not predict sexual orientation: all permutations are possible (Hellman et al., 1981). Indeed,in the cases studied by Garcia-Falgueras and Swaab, only 7 out of 11 were orientated towards females (i.e. nonhomosexual for their chromosomal sex, but homosexual for their gender identity). How could the same area of the brain regulate these two independent aspects of sexuality—though, it has to be said, there are indistinct boundaries between homosexuality, gender identity and other aspects of sexuality? For example, young boys that prefer to crossdress are likely to be homosexual, not transsexual, in adult life (Green, 1985).There is some disagreement about whether testosterone levels in the adult can alter the size or chemical structure of the MPOA in rodents (Davis et al., 1996; Ulibarri and Yahr,1993). Garcia-Falgueras and Swaab try to eliminate this as af actor in their study by looking at INAH3 in five orchidectomized (non-transsexual) men. Their results are not very helpful: there are no differences in INAH3 volume or neuronal number between these subjects and the control or MtF males, or females. Neuropeptide Y (NPY)-stained sections show a reduction in volume compared to control males. The interval between castration and death was very short in most of their cases. It is curious that structures inthe hypothalamus, a part of the brain closely associatedwith internal events in the body rather than those outside it, could determine sexual preference or gender identity.

Previous studies by the same lab (Zhou et al., 1995), as well as others, show structural differences associated with varieties of sexual behaviour and attitude in other areas of the brain, for example the bed nucleus of the striaterminalis (BST), which is linked both with the hypothalamus and the amygdala. The latter has more direct access to external stimuli, such as those determining sexual attractiveness. It seems that there may be a neural‘system’, rather than a single nodal area, that determines or influences the different parameters of human sexuality.Add to this the evident contribution of the cerebral cortex,involved in social awareness, attitudes, decision-making and the use of sex as a social instrument and we can see that the boundaries of the ‘sexual’ brain are as indistinct as the definition of sex itself.

But the significance of the Garcia-Falgueras and Swaabpaper is really as much political and even legal as it is neuroscientific. If there are demonstrable and functionally relevant features in the brain that underlie beliefs or proclivities that determine a person’s behaviour from an early age, and may be immutable, then the case for a redefinition of gender and for reassignment surgery in transsexuals is strengthened. There is still conflict between those who consider human sexuality to be either biologically or socially determined (the two, of course, are not mutually exclusive—as some seem to think—and must work together).

Future studies may uncover more exact neurobiological explanations for the strange human phenomenon of gender dysphoria, and this might help our understanding of more mainstream sexuality (Brunettiet al., 2008). Our view of homosexuality was altered byLe Vay’s findings on INAH3 (1991). One day, someone may uncover a neural feature (which we might call an abnormality) underlying other, less acceptable, traits such as paedophilia: what then? There are already suggestions that head injury before the age of 13 years is more common than usual in paedophiles (Blanchard et al., 2003).

I thank J. Bancroft, R. Green and M. Hines for their help
with this commentary.
Wellcome Trust.
Joe Herbert
Cambridge Centre for Brain Repair, Department of Clinical
Neurosciences and Department of Physiology, Development
and Neuroscience, University of Cambridge
E-mail: jh24@cam.ac.uk
Advance Access publication October 24, 2008


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3. Jill Davidson - January 26, 2010

Did you mean the American Psychiatric Association in your introductory statement? The other APA (the psychological one) is already on-record (August 2008) as opposed to discriminatory language with regard to gender variance: http://www.apa.org/about/governance/council/policy/transgender.aspx

4. Jill Davidson - January 26, 2010

Oy – it was painful at the end, though, wasn’t it? Why did the author have to call it the “strange human phenomenon of gender dysphoria?” I mean, my migraines are strange phenomena – but my gender? And then, bringing in pedophilia at the end.

Geekgirl - January 29, 2010

Hi Jill
I agree completely, it was painful at the end. Please remember that research papers are actually directed at an audience of other researchers who keep up with a field, they are more like chapters in a big book. A lot of people are studying pedophilia, which is actually more important to study since it is dysfunctional behavior that harms people. (I just report ’em). I did mean the American Psychological Association. There are earlier posts (I think…) on the call to end the use of words like gender dysphoria. I will be delighted to see that language go. Scientists and physicians sometimes change language slowly, often for bureaucratic reasons. Once a term becomes “formal” and understood across many languages, it is hard to change it so that everyone knows what is being said. But many newer papers by the leaders in this field have already written in a different style and I’m hopeful this will become the new standard.

5. Watching - January 26, 2010

When are we going to learn just how socially constructed gender identity is? There may be biological co-factors, but all one has to do is look at the incredible variations in (the multiple) gender types across the centuries and geography to see just how constructed it is. What is perceived to be masculine and what is feminine changes constantly. And environmental influences on biology must be considered–look at the changing size of the splenium. I’m glad to see the gender/sex connection complicated here, but I do not see the value in trying to determine any kind of biological causation for gender. And by the way, as much as I respect Simon Le Vay, in the realm of things I don’t think finding some biological links for male homosexuality is going to change much of anything. It’s a lesson in futility to think we might eliminate homophobia if people understood homosexuality as biological. It’ll still be framed as an abnormality, or deviance from the norm and only tolerated at best as long as we do not learn to accept that homosexual behavior is fine even if it is a choice and on par with heterosexuality, and understand sexuality as much more fluid than social norms presently allow.

Regarding gender dysphoria, any medical discussions should be accompanied by an understanding of current trans theory, queer theory, and the traditional medical model. Without understanding what’s coming from the evolving scholarship from those areas, neurobiology is fatally isolated.

Geekgirl - January 29, 2010

Hi Watching – thanks for stopping by. Hmm, I do see the value in this research. Studies have shown that those who disapprove of homosexuality believe it is a choice, those that are supportive of LGBT equality believe it is not a choice.
I would phrase my view point differently. I think it is sad that we have to do biological research in order to get people to accept variation in gender identity and sexual orientation. In fact, research in this area is miniscule because being gay is not a disorder. It makes more sense to give grant money to discover a cure for cancer than finding out why people are gay.
You are right. There will always be homophobia, just like we have racism, people waiting for the rapture, you name it. You are also right that this research may not be the key to persuading everyone. People are persuaded, educated or moved by many reasons. This is only one avenue. Studies have also shown that people who know someone gay, really knows them, about 85% support full equality for LGBT people. So we are most influenced by our human experiences. Which, in my mind, is the best persuader of all. Check out my About Me page. I could care less if science proves that gay people are normal. Because I’ve had gay friends for over thirty years and that is all the proof I need.

6. Warren - January 26, 2010

This: “on an equally important issue, that of gender identity (whether we think of ourselves as male or female), the experimental literature is silent. For good reason: animals cannot report, as humans can, on their gender identity, and no-one has found an indirect way to reveal the gender identity of a monkey, let alone a rat. There are no experimental models of transsexuality. So, studies on the neuroscience of human transsexuality are limited to man alone.”

Is not true. There is a lot of this type of research in ecotoxicology and environmental biology. Toxicologists have to study the effects of endocrine disrupting pollutants on animal reproductive development and behavior. I recently read a fantastic study about how pasture treated with sewage sludge that contained estrogen-acting chemicals resulted in the birth of male sheep who exhibited female behavior and were treated like females by the herd. The behaviors evaluated were not mating behaviors. And that’s just one study… before writing a whole article on a topic, one should first review the relevant literature.

Geekgirl - January 29, 2010

Hi Warren – thanks for stopping by. Yes, I’m aware of the studies that you are citing and I think I understand your point. I’ve posted about male sheep before. I think the point is a much simpler one. Does an anatomically male sheep that behaves like a female “think” it is a girl or a male? Do animals even have the ability to think that they have a gender identity at all?
Knowing what an animal thinks about anything has always been difficult research. We can observe anatomical changes, changes in hormone levels, changes in development and behavior. But it won’t tell us how the animal itself identifies.
We can’t even say that penguins that pair up identify as gay. All we know is, they pair up!

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