The Transgender Brain: New Insights

Pauline Anderson

May 16, 2018

NEW YORK — There's the male brain and the female brain, and now researchers believe there may also be the transgender brain.

Dr Murat Altinay

Generally, male and female brains differ with respect to total brain volume, gray matter volume, and cortical thickness. New imaging findings suggest that the brains of transgender individuals may "fall somewhere in between," at least from a volumetric standpoint, researcher Murat Altinay, MD, Center for Behavioral Health, Cleveland Clinic, Ohio, told Medscape Medical News.

"Classic medicine focuses on chromosomes, on genes, and on the body representation of gender, such as genital organs, but we're changing our focus to the brain, introducing the concept of 'brain gender' and saying that gender is actually in the brain," he said.

The findings were presented here at the American Psychiatric Association (APA) 2018 annual meeting.

Gender Is in the Brain

The term "transgender" refers to the mismatch between individuals' experienced or expressed gender and their biological sex at birth. Gender dysphoria describes the distress caused by this discrepancy, which can lead to social, occupational, and emotional impairment.

The investigators note that the underlying pathophysiology of gender dysphoria is not well understood. They point out that it is often confused with major depressive disorder.

To better understand gender dysphoria, the investigators searched PubMed for cross-sectional, prospective, retrospective, case-control, and randomized control trials and meta-analyses. They extracted age, sex, gender identity, hormone replacement therapy status, and surgical history, as well as differences in regional brain activation and connectivity.

The results of the analysis showed that certain areas of the brain, including the hypothalamus, the thalamus, the orbitofrontal cortex, and the insula, are more active in transgender females (male-to-female) than in cisgender male persons ("cisgender" refers to the correspondence between gender identity and birth sex).

Researchers also found differences in brain volume, including differences in cortical thickness and gray matter volume, between transgender and cisgender brains.

This difference was observed the brain's right and left hemispheres, the parietotemporal complex, the insula, and the medial occipital cortices; transgender females showed greater cortical thickness compared to cisgender males.

With this new analysis, Altinay and colleagues introduce the "brain gender" concept and argue that psychological processes such as "prediction error" and "cognitive dissonance" may play a role in gender dysphoria symptomatology.

Prediction error occurs when an individual's expectations or predictions in a situation (eg, "I am a woman; therefore, society should see me as a woman") are different from what actually happens (eg, society sees the individual as a man).

Cognitive dissonance refers to conflicting attitudes or beliefs that lead to a feeling of discomfort.

These concepts, said Altinay, may help experts better understand the brain's response to the mismatch between gender dysphoric individuals' inner perception (ie, how they see themselves) and external feedback (ie, the way society sees them).

Management of gender dysphoria may include hormonal treatments that change the secondary sex characteristics and expression, genital reconstruction surgeries, and facial reconstruction surgeries.

But the differences revealed in the neuroimaging data were notable even after patients began receiving these treatments. This is in line with the notion that gender dysphoria is more than merely an individual's failing to identify with the assigned sex at birth, said Altinay.

"When your body does not match your gender identity, of course, your body bothers you, but it's not the only source of the problem, because sometimes, even after certain treatments are given or certain surgeries are done, people can still feel dysphoric, so that's why we think dysphoria and gender are in the brain," he said.

These new results provide evidence that brain gender, or what Altinay calls "gender identity–associated brain organization," is real.

Gender Dysphoria Biomarker?

The findings also suggest activity in the body representation network (BRN), which includes the primary somatosensory cortex, the superior parietal lobe, and the insula, is unique in the transgender brain.

This, said Altinay, suggests that the BRN could be a neurologic biomarker for gender dysphoria, but he emphasized that research in this area "is at the beginning stages."

Altinay's next goal is to understand what happens in the brain, from a functional standpoint, when patients are exposed to situations that trigger gender dysphoria. He hypothesized that when individuals have such feelings, certain areas of brain should "light up."

The transgender brain may be differentiated at one of two key stages in its development — the prenatal or fetal phase and puberty.

"The brain goes through some structural and functional maturation during these phases," said Altinay. "I think we are realizing that in these phases, the brain develops in a different direction from a functional and structural, or volumetric, standpoint."

This may explain the functional and structural similarities between the transgender brain and its identified gender, he added.

One important reason to clarify the differences in the transgender brain is that doing so may prevent a misdiagnosis of depression, said Altinay.

"A lot of LGBT [lesbian, gay, bisexual, and transgender] people, and especially transgender people, are misdiagnosed as having a mood disorder or anxiety, but in many cases, what inexperienced clinicians see as mood disorder is actually gender dysphoria," he said.

Some research suggests that mood disorders are overdiagnosed in the transgender population, Altinay added.

"My goal is to help people understand that gender dysphoria and mood disorder are separate diagnoses," he noted.

Properly identifying gender dysphoria could prevent depression. "If gender dysphoria is not treated, it eventually leads to major depressive disorder," said Altinay.

It is important to help patients with gender dysphoria "live their true gender, live their experienced gender," he added.

The Governing Organ

Commenting on the findings for Medscape Medical News, Manpreet K. Singh, MD, assistant professor of psychiatry and behavioral sciences and director of the pediatric mood disorders program at Stanford University, in California, said researchers have known for some time that the brain is not either male or female and that there are degrees of maleness and femaleness in different brain regions.

She pointed to a "classic" behavioral observation, that boys tend to have externalizing disorders, such as oppositional defiant disorder and attention-deficit/hyperactivity disorder, whereas girls tend to have more internalizing disorders, such as anxiety and depression.

Singh and her colleagues are "very interested" in understanding this phenomenon, she said.

"Our group has looked at the brain to see if there might be some clues in understanding that, and, lo and behold, when we did analyses of various regions and attached to each region a sex differentiating score, we found that some regions were more male and other regions were more female," she said.

The sex of the human brain "can be conceptualized on a continuum," she added.

Although sex-differentiating organs such as the ovaries and the testes help determine whether someone is a boy or girl, these organs are regulated by the brain, noted Singh.

"The brain is the governing organ, and any dysregulation that occurs in the brain can absolutely change not just your maleness or femaleness from a biological perspective but also from a psychological perspective in terms of how you feel," she said.

Dr Altinay and Dr Singh have disclosed no relevant financial relationships.

American Psychiatric Association (APA) 2018. Abstract 7-78, presented May 8, 2018.

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