Tag Archives: sex differences

Increased Cortical Thickness in Male-to-Female Transsexualism – A Review and a Hypothesis

This study found that male-to-female transsexuals* (MTF) had thicker cortexes than control males did in certain areas of the brain. It is not clear what the differences mean.

We don’t know what caused the difference, we don’t know how the difference affects people, and we don’t know if the difference is related to gender identity, sexual orientation, or some other factor.

That’s the essence of the study; we don’t know.

Back to the study. The cerebral cortex is the outer layer of your brain. It is made up of gray matter which contains mostly neuronal cell bodies,

As with many studies, the difference they found might be related to gender identity or to sexual orientation. The MtF group included 6 people who were male-oriented and 18 who were female-oriented, so 25% of them were attracted to men. It is likely that 95% of the control males were attracted to women.

The authors suggest that:

“future studies need to explore the possibilities that brain anatomy in MTF transsexuals varies depending on whether they are attracted to men, attracted to women, or attracted to both. Ideally, those studies will also include heterosexual / homosexual control men, matched to MTF transsexuals with respect to their sexual orientation.

As with other studies, we don’t know what the practical effects of these differences might be. What does it do to you to have a thicker cortex? What does it mean if your cortex is thicker in the front versus the back of your brain? Does it matter if it is only thicker on the right side?

or as the authors put it:

“further research characterizing the relationships between cerebral micro-structure and macro-structure as well as brain function is clearly necessary before these regional structural differences (and any inherent hemispheric effects) can be precisely interpreted.”

The authors suggest that the thicker cortexes in the trans women (MtFs, i.e. born male) “resemble the direction of previously reported gender-typical pattern among non-transsexuals, such as thicker cortices in women than in men.”

In other words, they are similar to females, at least in terms of having thicker cortexes than males.

Maybe, maybe not.

This study did not look at any female brains, so we can’t know how the brains of the males or trans women would have compared to female controls.

Furthermore, studies have also linked thicker cortexes to obsessive-compulsive disorder (OCD), autism, social anxiety disorder (here and here), and, in children, to generalized anxiety disorder.**

There is even a study that found a small area*** of increased cortical thickness in people with xenomelia (the feeling that one of your limbs is foreign, also known as Body Identity Integretive Disorder).

Cortical thickness has also been linked to a positive trait; valuing religion or spirituality.

Finally, a couple of studies have found that meditation and sports training are associated with increased cortical thickness.

If we just go be the direction of the difference, the thicker cortex found in trans women could be linked to OCD, social anxiety disorder, autism, gender identity, xenomelia, spirituality, or life experiences.

These are not crazy possibilities; this Spanish study found that trans people had more social phobias than the general population. This Dutch study found that children and teens with gender dysphoria had a higher rate of autism spectrum disorder than the general population.

The important question is not is the cortex thicker, it’s where is the cortex thicker?

So where is the cortex thicker and what does it mean?

First of all, although some studies have found that females have thicker cortexes than males, the differences are not always in the same place in the brain.

This study found that females had thicker cortexes in the right inferior parietal and posterior temporal regions even without correcting for total brain volume (i.e. the males had bigger brains, but the females cortexes were thicker in these areas anyway). When they corrected for age and brain volume, females had thicker cortexes in the temporal and parietal lobes.

This study, on the other hand, found that females had thicker cortexes in the frontal, parietal, and occipital lobes.

And this study, found that females had thicker cortexes in the frontal, parietal, and occipital lobes on the left, and mostly the parietal lobe on the right. In the temporal lobe “small regions of the left and right caudal superior temporal gyrus (STG) and the left temporal pole showed significantly greater cortical thickness in women.”

Finally, this study found that females had thicker cortexes in all four lobes of the brain and on both sides, unlike the studies listed above.

This is like doing four studies comparing all the bones in men’s and women’s bodies.

One study finds that women have thicker arm and leg bones.

The next finds that they have thicker spines, ribs, and leg bones.

A third study finds thicker ribs, skulls, and elbows.

A fourth finds that women have thicker bones everywhere.

You wouldn’t be sure what this means about women’s bones. You wouldn’t even be sure if women’s arm bones were thicker than men’s without more studies.

The effects of having thicker bones would be very different if women had thicker ribs as opposed to thicker elbows. Knowing exactly where the bones were thicker would also be important if you were trying to figure out what exactly caused women to have thicker bones.

Going back to our brains, the frontal lobe is in the front, the occipital lobe is in the back.

The frontal lobe is involved in evaluating consequences and choosing the best action to take.

The occipital lobe is the visual processing center of the brain.

The parietal lobe integrates sensory information; it is also where we have our internal map of our own body.

The temporal lobe is involved in the retention of visual memories, processing sensory input, comprehending language, storing new memories, emotion, and deriving meaning.

So it matters a great deal where exactly women have thicker cortexes than men. In fact, it matters where exactly the difference in cortical thickness is within the lobes of the brain.

In short, we are still figuring out the differences between men and women when it comes to cortical thickness. What exactly are they and what do they mean? This makes it hard to draw any conclusions about whether or not trans women’s brains are like cis women’s.

To further complicate matters, this study found that age affected the sex differences in cortical thickness.

Going back to the original study, where were the trans women’s cortexes thicker than the control males?

In the left hemisphere, their cortexes were thicker in “the orbito-frontal cortex, the middle frontal gyrus, in the vicinity of the central sulcus (near midline), in perisylvian regions (close to the post central gyrus), as well as within the paracentral gyrus and orbito-frontal gyrus (medial surface).”

These are areas within the frontal lobe and the parietal lobe.

In the right hemisphere, their cortexes were thicker “along the post and pre central gyrus (expanding into middle frontal regions), the parietal cortex (near midline), the superior temporal sulcus, the inferior temporal gyrus, as well as within the orbito-frontal, fusiform, and lingual gyrus, and the precuneus (medial surface).”

These areas are within the frontal lobe, the parietal lobe, the temporal lobe, and the orbital lobe.

Although the areas where trans women have thicker cortexes are in all four lobes of the brain, it looks like the total area where they have thicker cortexes is not large (see Figure 1).

It is very hard to compare, but it does not look like the areas where trans women have thicker cortexes than men in this study are the same as the areas where females have thicker cortexes than males in other studies (Figure from the first study of males and females, above).

It doesn’t look like the areas where the trans women’s cortexes were thicker are the same as in the studies that linked increased cortical thickness to OCD, although there might be some overlap with the patients who had social anxiety disorder.**** Perhaps one of the trans women had social anxiety disorder and it affected part of the results.

On the other hand what if the areas of increased cortical thickness in trans women have to do with something specifically about trans women?

I want to stress that we do not know what the areas of increased cortical thickness mean functionally for trans women or cis women or people with OCD or people who meditate. Many areas of the brain are involved in more than one process. In addition, it may be that what we are looking for is a network of areas, not just one area.

We really can’t tell what it means that trans women have thicker cortexes where they do.

Nevertheless, I want to offer up a hypothesis that I hope someone will test.

Looking at the right side of the brain, the areas where trans women’s cortexes are thicker seem to have something to do with the body and perception.

According to my trusty Wikipedia,

“The postcentral gyrus is the location of the primary somatosensory cortex, the main sensory receptive area for the sense of touch. Like other sensory areas, there is a map of sensory space in this location, called the sensory homunculus.”

The precentral gyrus includes the primary motor cortex which works with other areas of the brain to plan and execute movements. It also includes a map of motor areas corresponding to body parts.

The parietal lobe integrates sensory information.

The superior temporal sulcus is involved in the perception of where others are gazing and the perception of biological motion. It may have multisensory processing capabilities.

The inferior temporal gyrus is associated with visual processing and possibly face perception.

The orbitofrontal gyrus is part of the orbitofrontal cortex which is involved in the cognitive processing of decision-making; it doesn’t seem to fit the pattern here.

The fusiform gyrus  is involved in face and body recognition. Furthermore, “Increased neurophysiological activity in the fusiform face area may produce hallucinations of faces.”

The lingual gyrus is linked to processing vision.

The precuneus is part of the parietal lobe. It includes three subdivisions: a sensorimotor region,  a cognitive/associative region, and a visual posterior region. It is involved in sense of self, memory, and motor imagery and coordination.

On the left side of the brain, most of the areas of relative cortical thickness do not seem to be related to the body. However, the paracentral lobule includes the supplementary motor area in the frontal lobe and part of the parietal lobe.

Could it be that the increased cortical thickness on the right side is somehow related to trans women’s negative feelings about their bodies?

Could something in their body maps or perception be causing their dysphoria?

Could their gender dysphoria have changed their brains?

This might be an area for future research.

Future research into gender identity and the brain should definitely include some gay men and lesbian controls so that we can separate out the effects of gender identity and sexual orientation.

It would also be a good idea for future studies to include more information on other conditions that might affect their results such as depression, anxiety, Aspergers syndrome, etc. Although this study says that the subjects were free of psychosis, they do not discuss issues like OCD, etc.

I don’t think the best approach would be to exclude trans people with other conditions because part of the reality of gender dysphoria is that some people have more than one condition. If we really want to understand what is happening, we need to include that data. However, it might make sense to include some controls who had social anxiety disorder, etc., if only to find where the differences are.

Back, one last time to the study.

The authors’ discussion of their results includes one odd statement:  “In addition, our current findings of significantly thicker cortices in MTF transsexuals than in control men correspond with previous in vivo outcomes revealing that MTF transsexuals show significantly larger gray matter volumes than control men.”

This is an exaggeration of the results of an earlier study that they did on gray matter volume in trans women’s brains.

This earlier study found that trans women’s brains were more like men’s brains in 18 out of 20 areas of the brain. In two areas, the left and right putamen, trans women had more gray matter than both males and females, although within the average range of the females.

Their previous findings could be better summarized as trans women have gray matter volumes that match men’s except in the putamen.

This study did not look at the putamen as it is not in the cortex. The increased gray matter volume in the putamen found in the earlier study is irrelevant to this study.

Actually, at first glance the findings of this study don’t fit well with the findings of the previous study. The cortex is made up of gray matter, so you might expect its thickness to be related to the volume of gray matter. Why do trans women have gray matter volumes that are equal to or less than cis men’s but cortexes that are thicker?

The authors go on to address this question:

Nevertheless, it appears rather surprising that the previous whole-brain approach analysing gray matter did not detect any group differences in cortical regions (e.g., the ones revealed in the current study directed at cortical thickness). It is possible, however, that these two anatomical measurements reflect slightly different aspects on a micro-anatomical level as also suggested by studies investigating direct correlations between cortical thickness and gray matter concentration. Importantly, the current approach also provides an additional dimension of cortical morphology such as its thickness in millimeters, which is not directly captured by voxel-wise analyses of signal intensity changes throughout the brain.

In other words measurements of cortical thickness and gray matter volume may not be the same thing. It is possible that trans women’s gray matter volume is like men’s but their cerebral cortex is thicker in certain areas.

It is still not clear what it means that trans women’s cerebral cortexes are thicker than control males in certain areas.

We don’t know what the difference means functionally.

We don’t know if the difference is related to gender identity, sexual orientation, or some other factor.

We don’t know how the trans women’s cortical thickness would have compared to females since there were no female controls in the study.

We can’t say that trans women’s brains are like females’ brains since both have thicker cortexes than males because a) other factors like social anxiety disorder can make people have thicker cortexes; b) we aren’t sure exactly where females’ cortexes are thicker than males; and c) it looks like trans women and females’ cortexes thicker than males in different places.

And we don’t know if the difference in cortical thickness is related to body perception and sensory integration.

Original Study:

Increased Cortical Thickness in Male-to-Female Transsexualism by Eileen Luders, Francisco J. Sánchez, Duygu Tosun, David W. Shattuck, Christian Gaser, Eric Vilain, and Arthur W. Toga in J Behav Brain Sci. Aug 2012: 2(3): 357-362.

* I am using the language of the study.

** In general, a thicker cortex is probably a good thing; it is associated with meditation and learning. In addition, your cortex thins with age. The volume of the gray matter in your brain also goes down with age or due to illnesses such as depression.

*** the right central sulcus. I thought you’d never ask. And yes, trans women had a thicker central sulcus than control males, but it was on the left side and the overall pattern is different; patients with xenomelia mostly had areas where their cortex was thinner, not thicker. Then again, it might be worth looking further at the central sulcus in trans people’s brains.

**** The study of patients with OCD found that their cortexes were thicker in the right inferior frontal cortex and the right middle temporal gyrus.

This study suggests that the areas of cortical thickness in autism change with age. I don’t see how to compare the data on autism to the data on trans women.

One study of patients with social anxiety disorder found that they had increased cortical thickness in the left inferior temporal cortex. Trans women had increased cortical thickness in the right inferior temporal gyrus – as well as many other areas not found with social anxiety disorder.

Another study of people with social anxiety disorder found that they had increased cortical thickness in two clusters: “One was located in the right middle frontal gyrus extending into superior frontal sulcus, belonging to the dorsolateral prefrontal cortex (DLPFC, Brodmann areas 6/8/9/46). The other covered right superior parietal lobule and angular gyrus and extended in part into right precuneus and inferior parietal lobule (Brodmann areas 7/39/19).”

Trans women also had increased cortical thickness in the right middle frontal region, the right parietal cortex (near the midline), and the precuneus – but they had other areas of increased thickness as well.

Perhaps one of the trans women in the study had social anxiety disorder and it explained some of the areas of increased cortical thickness, but not all.

Or perhaps both conditions involve similar areas of the brain.

Regional Grey Matter Structure Differences between Transsexuals and Healthy Controls—A Voxel Based Morphometry Study – Review

This is a study with intriguing results. The study also has some frustrating flaws.

One of the most interesting things about the study is this:

“The regions found affected in our study are mainly involved in neural networks playing role in body perception, including memory retrieval, self-awareness, visual processing, body and face recognition and sensorimotor functions.”

In other words, gender dysphoria may be linked in some way to body perception.

The study found three types of differences in the brain:

In some areas of the brain trans people had less gray matter than cis people. This suggests that gender dysphoria might be caused in part by differences in body perception – or that gender dysphoria changes areas of the brain related to body perception.

In some areas biological males had more gray matter, in some areas biological females had more gray matter. Males generally have a larger volume of gray matter than females. Other studies have found regions where females have a larger volume of gray matter and regions where males have a larger volume, but there doesn’t seem to be an accepted map of which regions are which yet.

In some areas of the brain the trans people had gray matter volumes that were more like controls of the same sexual orientation and gender identity.

So the biggest flaw of the study is that they don’t control for sexual orientation.

Instead they specifically selected trans people who were attracted to members of their biological sex and then chose controls who shared their age and gender identity.

The authors do not discuss the sexual orientation of the control group, but 95% of the population is attracted to the opposite sex.

Thus, as in a number of other studies,* when the authors compare trans men (born female) to control females, they are comparing a group of people attracted to females to a group of people attracted to males. And when they compare the trans men to control males, they are comparing two groups of people attracted to women.

We know that sexual orientation can affect brain anatomy, so we can’t be sure if we are seeing differences due to gender identity or to sexual orientation.

Studies of gender identity need to start including some gay and lesbian cis people in their control groups.

In addition, if we keep leaving out trans people based on their sexual orientation, we are not properly studying gender dysphoria. About half of all trans women are attracted to females; we can’t just ignore them. We need to understand their brains, too.

A couple of other flaws:

1. The authors never discuss the sex differences they found. What do they mean? Do biological males and females process information about their body differently? How are these differences related to the differences between people with a female or male gender identity?

2. The authors don’t say whether or not they controlled for depression. Depression generally seems to decrease the volume of gray matter in the brain. The control subjects were screened to make sure they had no psychiatric disorders. Psychiatric data was collected on the people with gender dysphoria, but they don’t say if they excluded any trans people with psychiatric disorders like depression.**

People with gender dysphoria are more likely to be depressed than the general population. Since the results of the study involve the volume of gray matter in the brain, it would be important to control for depression – and possibly anxiety, etc.

In short – this study found an intriguing link between gender dysphoria and gray matter volume in areas of the brain that are related to body perception. They found some areas of the brain where trans people and cis people differ. They found some areas of the brain where people with gender dysphoria may be more like people who share their gender identity rather than their biological sex, BUT since they also shared the same sexual orientation, we can’t be sure. In addition, the study found a number of areas where biological sex was more important than gender identity. Finally, it is not clear if they controlled for depression and anxiety which could also have affected their results.

This is part I of my review. I will address specifics of the study in a future article or articles.

Original Article:

Regional Grey Matter Structure Differences between Transsexuals and Healthy Controls – A Voxel Based Morphometry Study by Lajos Simon, Lajos R. Kozák, Viktória Simon mail, Pál Czobor, Zsolt Unoka, Ádám Szabó, Gábor Csukly in PLOS one, December 31, 2013. 

 

*This is not the first study of gender identity and the brain to look only at trans people who were sexually attracted to their birth sex. See also, here and here. I think there are more studies that do this that I haven’t reviewed yet.

This study found that trans women’s brains were more like male controls than females; I think that the people doing these studies are trying to avoid a similar result by only looking at trans people who are attracted to their birth sex.

Except that doing this means they may be studying sexual orientation, not gender identity.

It also means that they don’t know if the brains of trans people attracted to their birth sex actually are different from the brains of trans people who aren’t attracted to their birth sex because, damn it, they aren’t looking!

** The authors say they excluded people with gender dysphoria from the study if they a) were “nonhomosexual,” b) had previously taken hormones, c) had a known chromosomal or hormonal disorder, or d) had a neurological disorder. In addition, when patients were diagnosed with gender dysphoria, they were assessed for psychiatric problems in order to “exclude the presence of other mental disorder behind the symptoms of GID.” (GID=gender identity disorder=the older name for gender dysphoria.) Depression would not rule out gender dysphoria, however. It looks like patients with both gender dysphoria and depression could have been included in this study.

A brain sexual dimorphism controlled by adult circulating androgens

This is a study about rats. As always, we don’t know if what works for them is true of humans. The study does, however, point to an important factor to consider in any research on gender identity.

The authors found that they could completely change an observed sex difference in adult rats’ brains by changing their sex hormones. Earlier exposure to sex hormones made no difference.

This means that this observed sex difference was completely caused by adult circulating androgens.

The authors suggest that this might also happen in human brains. They refer to studies of the structures in transsexual brains and suggest that we can’t be sure that observed differences were caused by differences in the early development of the brain. They might have been caused by taking cross-sex hormones.

This study is from 1999, so they are referring to some of the early work on gender identity and the brain by Swaab et al and Zhou et al. Those studies included the brains of trans people who had been taking hormones.

Those studies are probably obsolete; newer studies have indeed found that taking sex hormones changes human brains, including the area Swaab et al and Zhou et al talked about, the hypothalmus.

This study of hormones in adult rat brains would not affect studies if they a) look at trans people who have not yet taken any hormones and b) test people to make sure their hormonal levels are in the normal range for their biological sex.*

It is also possible that some areas of the brain are controlled by circulating hormones and some are affected by earlier exposure to hormones as well as circulating hormones. The authors cite examples where castration dramatically changed areas of the rat brain, but did not completely reverse the sex difference.

The authors also discuss studies that found you could change a bird’s brain by changing its hormones.

They conclude by discussing the ways adult hormones affect the human brain.

“Human behavior is also subject to the activational effects of androgens. Transsexuals treated with cross-sex hormones display sex reversals in their cognitive abilities, emotional tendencies, and libido (34, 35), and sex offenders are sometimes treated with antiandrogens to reduce their sex drive (36). The sociosexual changes observed in these groups most likely reflect structural and physiological plasticity in steroid-sensitive areas within the brain. The volumetric sex reversal reported here substantiates the possibility that hormones in adulthood can dramatically affect the structure of a brain region concerned with sexual behavior. Although the volumetric sexual dimorphism of the MePD is more modest than other animal models [a difference of 150% rather than 400–600% (31)], the extent of the MePD sexual dimorphism in rats in quite comparable to reported sexual dimorphisms in the human brain (1–6) and therefore supports the possibility that sexual dimorphisms of the human brain are caused solely by circulating steroids in adulthood.”

We can’t generalize from a study of rat brains to human brains, but this study does underline the importance of using trans people who have not taken cross-sex hormones if you want to study gender identity and the brain.

Original Article:

A brain sexual dimorphism controlled by adult circulating androgens by Bradley M. Cooke, Golnaz Tabibnia, and S. Marc Breedlove in Proc. Natl. Acad. Sci. USA Vol. 96, pp. 7538–7540, June 1999.

*A Japanese study found that many of the female-to-male transsexuals applying to their clinic had polycystic ovarian syndrome (PCOS); PCOS causes high levels of androgens.

(Bold added by George Davis.)

Neural, not gonadal, origin of brain sex differences in a gynandromorphic finch – Brief Review

This is a study about birds, not humans. We cannot generalize from bird brains to human brains. The results can only suggest possibilities to study.

It is, however, a fascinating study. The authors found that the bird’s brain cells were influenced by their genetic sex, not just their hormones.

They looked at a rare case of a bird whose brain was genetically male in one half and genetically female in the other half. The two halves had different neural song circuits, with one half being more masculine. Since both halves of the brain were exposed to the same hormones, the difference may have been due to the genes of the brain cells.

The study suggests that the sex chromosomes in the brain can themselves affect the brain.

The authors conclude:

“These results provide the strongest evidence to date that sex differences in the song circuit of zebra finches originate partly because of differences in the actions of sex chromosome genes acting locally within the brain.”

Furthermore, there may be other animals whose sex chromosome genes play a role in creating sex differences.

“This system thus represents one of a growing number of model systems in which the actions of sex chromosome genes are implicated in sexual differentiation of nongonadal tissues in birds and mammals. Other sexually dimorphic phenotypes influenced by the genetic sex of cells include the size of mammalian embryos (28), external genitalia of tammar wallabies (29), aggression in mice (30, 31), phenotype of midbrain and hypothalamic cells in rats and mice (32, 33), and vasopressinergic innervation of the lateral septum of mice (34). Further work is needed to resolve how the hormonal and cell-autonomous mechanisms interact to produce sex differences in brain phenotype and disease.”

The study has one weakness, however: the  sample size is small, as small as you can get, in fact. This result might turn out to be an anomaly.

Original Study:

Neural, not gonadal, origin of brain sex differences in a gynandromorphic finch by Robert J. Agate, William Grisham, Juli Wade, Suzanne MannJohn WingfieldCarolyn SchanenAarno Palotie, and Arthur P. Arnold in Proceedings of the National Academy of Sciences of the United States of America, vol. 100 no. 8,  April 15th, 2003, 4873–4878.

Regional gray matter variation in male-to-female transsexualism – Review

This article found that trans women’s brains are more similar to men’s brains than cis women’s brains, at least in terms of the pattern of gray matter variation.

They also found that trans women’s brains had more gray matter in the putamen than both cis men and cis women, although the difference was only significant for cis men.*

The authors found 20 areas of the brain where women had more gray matter than men. The male-to-female transsexuals (trans women) had the smallest volume of gray matter in these areas, but their data spectrum mostly overlapped with the men’s.

In two areas of the brain, the left and right putamen, male-to-female transsexuals had the largest volume of gray matter.**

“…the gray matter volume of this particular structure in the MTF transsexual group was both larger than in males and within the average range of females.”

Gray matter, in case you’re wondering, contains more neuronal cell bodies. White matter is mostly made up of axons that transmit signals within the brain. Previous studies have found that there are sex differences in the distribution of gray matter in the brain.

The authors describe the putamen as being “feminized” in MTF transsexuals. That might be, but it might also be that their putamens are simply different from cis people’s for some other reason.

In addition, the putamen has more gray matter in women than in men, but the trans women’s putamens had more gray matter than either, although the difference between trans women and cis women was probably not significant.**

The authors conclude:

“Overall, our study provides evidence that MTF transsexuals possess regional gray matter volumes mostly consistent with control males. However, the putamen was found to be “feminized” in MTF transsexuals….”

“Taken together, these findings lend support to the hypothesis that specific neuroanatomical features are associated with transsexual identity, where the particular role of the putamen requires investigation in future studies.”

The study results also support the idea that trans women’s brains are more similar to men’s brains than to cis women’s brains. Most of the time when men’s and women’s brains differ, the trans women’s brains were like men’s.

In addition, the authors briefly mention a few areas where women’s and men’s brains were similar, but trans women’s brains were different from cis women’s (see details of study below).

On the other hand, we definitely need more studies of the putamen and gender dysphoria.

As the authors point out, we do not know if the differences in the putamen are the cause or result of gender dysphoria – or if the differences are caused by another factor that also causes gender dysphoria.

It is also possible that the observed differences are caused by sexual orientation, not gender identity. The authors explain that their sample included 6 male-oriented people (25%) and 18 female-oriented people (75%). They did not know the sexual orientation of their control groups, but it is likely that 95% of the males were attracted to females and 95% of the females were attracted to males.

Their sample also included more left-handed people than the control groups. It is possible that handedness affects the size of the putamen in some way.

Another huge issue is that we have no flipping idea what the results mean. The putamen is an area of the brain that is believed to be involved in many different functions including motor skills, memory, and processing sensory information. If it is involved in gender dysphoria, we need studies to figure out how.

Hopefully we will see some studies confirming this result, this time with a control group that includes gay men and lesbians. The study should also control for handedness.

Then we will need more studies looking at exactly what is going on.

Original Article:

Regional gray matter variation in male-to-female transsexualism by Luders E, Sánchez FJ, Gaser C, Toga AW, Narr KL, Hamilton LS, Vilain E. in Neuroimage. 2009 Jul 15;46(4):904-7.

Some details of the study:

The authors looked at 24 trans women recruited through the community organizations and professionals who serve trans people. Their average age was 43 (range 23-72). They were genetic males (they had the SRY gene),*** they were free of psychoses, and they passed a physical and neurological exam. 76% of them were right-handed, compared to 90% or more of the controls.

None of them were on hormones, although they all intended to take them.

More about the results:

“females had more gray matter than males in large portions of the brain… Similarly, females had more gray matter than MTF transsexuals… Although the differences between females and MTF transsexuals did partly overlap with the difference between females and males…, they were spatially more extended, and also evident in a few regions where females and males did not differ… There was no region where females had significantly less gray matter than males… or MTF transsexuals… Similarly, there was no region where MTF transsexuals had significantly less gray matter than males… MTF transsexuals, however, showed significantly more gray matter than males in the right putamen… MTF transsexuals also showed significantly more gray matter than males in the left putamen when findings were not corrected for multiple comparisons (p<0.001, maps not shown).”

I am intrigued by the mention of a few regions where females and males did not differ but females had more gray matter than MTF transsexuals. I wish the authors had discussed these areas. Perhaps they would shed some additional light on gender dysphoria.

*The box plot data on the trans women’s putamen looks pretty different from the cis women’s data. Their median value is higher and their range seems to be much bigger and go up higher. However, the difference is probably not significant since the authors say elsewhere that there was no area where females had significantly less gray matter than trans women.

** It may be that the difference was only statistically significant in the right putamen. Elsewhere in the study the authors say that trans women had significantly more gray matter than males in the left putamen only when the findings were not corrected for multiple comparisons. Because brain scans involve collecting so many data points, the chances of finding correlations by chance are much greater. Thus you have to make corrections. On the other hand, in this case, the other half of the putamen was different at a stastically significant level.

*** Zoe Brain has pointed out that someone could have the SRY gene, but still have unusual chromosomes, if they had Kleinfelter’s syndrome (47xxy) or mosaicism (46xx/46xy). Her interpretation of this study is quite different from mine, but well worth reading.