Monthly Archives: September 2014

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.)

Depression and Gray Matter in the Brain

Depression causes gray matter in the brain to decrease. This is important to keep in mind when looking at studies of trans people’s brains as many trans people have experienced depression.

These are just a few links to studies looking at depression’s effects on the brain. A smaller hippocampus seems to be particularly related to depression, although studies have also found a link to an overall decrease in gray matter.

The bottom line is that studies of gray matter and gender identity need to take into account past and present depression in both trans people and controls.

For anyone with depression, the bad news is that it’s not good for your brain. The good news is that you can do things for your brain – exercise, meditate, and learn.

You may be able increase the volume of your hippocampus with regular exercise. Eight weeks of mindfulness meditation increases the volume of your hippocampus and may increase the gray matter volume in other areas of your brain as well. You can increase your gray matter by learning a new skill like juggling or by reading text written backwards. Going to medical school affects your gray matter.

Back to the studies and the link between gray matter volume and depression.

State-dependent changes in hippocampal grey matter in depression. 

This study found that patients who were currently depressed had lower volumes of gray matter in the hippocampus compared to both healthy controls and people who had had depression before but were not currently depressed. After taking citalopram, the patients with current depression had more gray matter in the hippocampus.

Insular and Hippocampal Gray Matter Volume Reductions in Patients with Major Depressive Disorder.

This study found that patients with major depressive disorder had “a strong gray-matter reduction in the right anterior insula. In addition, region-of-interest analyses revealed significant gray-matter reductions in the hippocampal formation.”

The effects were stronger for people who had had more episodes of depression than people who had only had one episode.

The more episodes of depression a patient had, the less gray-matter volume they had in the right hippocampus and right amygdala.

They conclude:

“The anterior insula gray matter structure appears to be strongly affected in major depressive disorder and might play an important role in the neurobiology of depression. The hippocampal and amygdala volume loss cumulating with the number of episodes might be explained either by repeated neurotoxic stress or alternatively by higher relapse rates in patients showing hippocampal atrophy.”

In other words, having depression might affect the hippocampus or having a small hippocampus might make you get depressed more often.

Association of Depression Duration With Reduction of Global Cerebral Gray Matter Volume in Female Patients With Recurrent Major Depressive Disorder

This study found that the more months the patients had spent being depressed, the less total cerebral gray matter they had. More months of depression was also linked to less frontal gray matter, less temporal gray matter, and less parietal gray matter. The study only included female patients who had recurrent depression. They did not control for the anti-depressants the patients used, so it is possible that the medicines affected their gray matter.

Gray matter volume abnormalities in individuals with cognitive vulnerability to depression: A voxel-based morphometry study.

This study looked at people who don’t have depression but who might be vulnerable to it. The “cognitively vulnerable” group was chosen by their answers to two questionnaires. The first questionnaire looked at thinking styles that may contribute to depression – people may be vulnerable to depression based on how they think about causal attributions, consequences, and self-worth characteristics. The second questionnaire asked about symptoms of depression.

Cognitively vulnerable people had less gray matter volume in the left precentral gyrus and right fusiform gyrus compared to controls. In addition their right fusiform gyrus and right thalamus were smaller compared to people who had major depressive disorder. Patients with major depressive disorder had reduced gray matter volume in the left precentral gyrus and increased gray matter volume in the right thalamus.

They conclude:

“Reductions in brain gray matter volume exist widely in individuals with CVD. In addition, there exist similar abnormalities in gray matter volume in both CVD subjects and MDD patients. Reductions of gray matter volume in the left precentral gyrus might be correlated to the negative cognitive styles, as well as an increased risk for depression.”

Of course, we don’t know which way the causality goes – is the cognitive style causing a lower gray matter volume in the left precentral gyrus or is the lower volume of gray matter causing the cognitive style?

Widespread reductions in gray matter volume in depression.

This study found that people with major depressive disorder had 4.4% less global gray matter volume than controls. This would be the decrease expected in 14 years of normal aging.

The differences were greatest in the front and temporal lobes, but there were also significant differences in the parietal and occipital lobes.

There was not a significant difference in the cerebellar volumes.

The cortex was thinner in the left medial orbitofrontal cortex for the patients with depression.

The authors conclude:

“Our data demonstrate conclusively that widespread GM volume abnormalities are present in patients with depression. These alterations are substantial, corresponding to the amount of GM volume loss that, when averaged over the whole brain, would be expected from nearly 14 years of normal aging. The GM loss is also highly regionally specific, with focal regions showing decreases in GM volumes of nearly twice the magnitude of the global measure. The distributed and regionally specific nature of these alterations provides compelling support for considering MDD as a condition that involves the impairment of networks across the brain.”

Small frontal gray matter volume in first-episode depression patients.

This study found that patients who had had their first episode of depression had less gray matter volume in the frontal lobe than healthy controls. The lower volume was not correlated with length or severity of the illness. The patients had not yet taken any medication for their depression. The authors suggest that the changes in gray matter could have occurred before the symptoms of depression. (Although they also could have been caused by the depression, we really can’t tell.)

Anomalous Gray Matter Structural Networks in Major Depressive Disorder

This study found that the gray matter in people with depression is connected differently from in controls.

They say:

“Depressed participants had significantly decreased clustering in their brain networks across a range of network densities. Compared with control subjects, depressed participants had fewer hubs primarily in medial frontal and medial temporal areas, had higher degree in the left supramarginal gyrus and right gyrus rectus, and had higher betweenness in the right amygdala and left medial orbitofrontal gyrus.”

and they conclude:

“Networks of depressed individuals are characterized by a less efficient organization involving decreased regional connectivity compared with control subjects. Regional connections in the amygdala and medial prefrontal cortex may play a role in maintaining or adapting to depressive pathology.”

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.

Exploring gender identity within the context of Asperger’s syndrome – Review

This is a thesis from 2012.

According to the abstract, the author interviewed adult men with Aspergers about their “perceptions of masculinity, gender-typed behaviours, relationships, and societal influences.”

She found that “for participants, identifying with male gender provides a platform for fitting in by allowing them to learn from societal stereotypes and rehearse playing ‘male’ roles. Participants displayed ambivalence in their feelings of being drawn to the perceived safety of females but resenting the ‘feminine’ side of themselves.”

Based on her study and the literature on gender identity, she makes recommendations for professionals and parents of children with Aspergers about potential gender identity confusion.

Unfortunately, I am not able to read it online. Perhaps someone else can find out what the author is recommending for parents!

Exploring gender identity within the context of Asperger’s syndrome by Victoria Elliott.

Gender and Autism – an article

This is an excellent article reviewing research on gender and autism. I highly recommend it.

Gender and Autism: a Preliminary Survey Post on the blog “Musings of an Aspie.”

The author discusses the “extreme male brain” theory of autism and suggests some alternatives.

She also talks about factors that might influence how people with autism spectrum disorders experience gender:

“This raises the question of what role being autistic might play in the formation of our personal experience of gender. For example, autistic children are less sensitive to social cues than typical children and may not make friends with or become part of groups of same-gender peers. If we’re not tuned in to what the social norms for children of our gender are, we’re less likely to adopt them early in life.

There may also be an aspect of autistic-related body dysmorphia in general that factors into gender dysphoria for some autistic individuals. Many autistic people have difficulty feeling connected to their physical selves or being physically comfortable with their body.

Finally, there is the issue of sensory sensitivities. Dressing or presenting androgynously may be a result of gender dysphoria or it may be related to avoiding sensory triggers associated with certain types, textures or styles of clothing.”

Enjoy the article!