Gender Dysphoria

Lasya Kambhampati


Gender dysphoria, which sometimes manifests itself as transgenderism, is a feeling of disconnect between the gender one identifies as and the natal (assigned) sex. Scientists have attempted since the 1990s to understand how or if the brain changes in transgender people and what differences exist between transgender (trans) and cisgender or cis (those who identify with their natal sex) brains. There is much left to discover, but intriguing results have already been unearthed.


Why It Occurs?

There are many ideas as to why gender dysphoria occurs. One hypothesis claims that “sexual differentiation of the genitals occurs separately from the sexual differentiation of the brain in utero”[2]. This theory implies that gender is determined in the womb, which is a controversial idea. Many scientists disagree with this developmental mismatch hypothesis and believe that a variety of factors can influence transgenderism, including events occurring after birth. Current research provides conflicting evidence towards the developmental mismatch hypothesis, suggesting that we need to continue developing our current theories in order to find something that aligns better with the data that we have collected so far.

Effects on Brain

Specific areas of the brain can show the differences and similarities between cis and trans brains. The thalamus and putamen is important in self-perception, but comparisons between cis and trans people have had inconsistent results [1].  Cortical thickness, which is influential in determining cognitive ability, has been shown to have an overall similar depth in both cis and trans brains. But there are differences in specific regions [7]. Particularly, the left superior medial frontal cortex, right cerebellum, left superior posterior hemisphere of cerebellum, and hypothalamus are different in transgender adolescents [1]. A 2013 study explored these specific differences in detail.  In transgender women, “the central subdivision of the bed nucleus of the stria terminalis”, whose function is tied to sexual behavior, was found to be closer in size to cis women than cis men [3]. This same relation was later extended to trans and cis men in a later study [4].

In Vienna, a study conducted by Dr. Kranz measured mean diffusivity in cis/trans brains. Diffusion tensor imaging is used to map the diffusion of water in relation to spatial location, allowing doctors to examine microscopic differences in brain structure. Using this tool, researchers can determine mean diffusivity in the brain. Results showed that cisgender women had the highest values and cisgender men had the lowest, whereas transgender men and women fell in between. The researchers hypothesize that the “hormonal environment before or soon after birth” accounted for this finding, providing support for the developmental mismatch theory [6]. A separate study conducted by Dr. Baker investigated which parts of the brain were activated in spatial reasoning tasks in trans and cis boys. Previous studies had shown that men and women used different brain areas while doing these tasks. Dr. Baker’s investigation showed that both trans and cis boys exhibited similar levels of activation in certain areas [5].  Although significant differences have been found in the brains of trans individuals, most studies indicate that trans brains have more in common with cis people who share the trans subject’s chosen gender.

Connectivity in the Brain

In Sweden, Dr. Ivanka Savic has done interesting research on how the brain’s neural network reflects the gender dysphoria, specifically the feeling of not belonging in one’s body, that trans people experience. Using fMRI, she found that when compared to cisgender members of both sexes, transgender men had less connectivity between anterior cingulate, posterior cingulate, and precuneus when they viewed images of themselves. If they were instead shown images in which they appeared to be more male (the gender they identify as but not necessarily the gender they were assigned at birth), the connectivity between those regions seemed to have increased. The cingulate regions and precuneus are important in connections between self and body, suggesting that a weak self-body connection may be related to the feeling of “not belonging” in one’s own body that many trans people experience.

Future Directions

One of the main concerns with the results of this research is ensuring that there isn’t a leap between brain structures and gender dysphoria; just because it seems like these two concepts are related doesn’t mean they are [1]. Although we now know more about transgenderism and its relation to the brain, there is still more to explore before we can claim to have a complete understanding. For example,  conducting more studies with patients who have undergone or are undergoing hormone therapy may allow us to monitor not only the intended changes that hormone therapy causes, which include changes in voice and fat distribution, but also potential changes in brain physiology. Another question left to be answered is whether male-to-female and female-to-male transitions cause different changes in the brain [8]. Still, more research topics remain open for investigation, such as differences in the timing of the onset of gender dysphoria. Hopefully, further research will allow scientists to investigate not only transgenderism, but also gender itself from a neurophysiological perspective.


Transgender men: female to male change

Transgender women: male to female change

Cisgender: individuals who identify with natal sex


  1. Smith, Elke. (2015). The transsexual brain - A review of findings on the neural basis of transexualism. Neuroscience Biobehavioral R. 59. Retrieved 22/11/2018

  2. Hoekzema, Elseline. (2015). Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain. Psychoneuroendocrinology. 59. Retrieved 22/11/2018

  3. Kranz, Georg. (2014). White matter microstructure in transsexuals and controls investigated by diffusion tensor imaging. J neurosci. 12. Retrieved 22/11/2018

  4. Sarah M Burke, Baudewijntje P. C. Kreukels, Peggy T. Cohen-Kettenis, Dick J. Veltman, Daniel Klink, Julie Bakker. (2016). Male-typical visuospatial functioning in gynephilic girls with gender dysphoria - organizational and activational effects of testosterone. J Psychiatry Neurosci. 41. Retrieved 22/11/2018

  5. Frank P M Kruijver, J N Zhou, Chris Pool, Michel A. Hofman, Louis J Gooren, Dick F. Swaab. (2000). Male-to-female transsexuals have female neuron numbers in a limbic nucleus. J Clin Endocrinol Metab. 85. Retrieved 22/11/2108

  6. Zhou, Jiang - Ning. Hofman, Michel. Swaab, Dick. Gooren, Louis. (1995). A sex difference in the human brain and its relation to transsexuality. Nature. 68. Retrieved 22/11/2018

  7. Bao, Ai-Min. Swaab, Dick. (2011). Sexual differentiation of the human brain: Relation to gender identity, sexual orientation and neuropsychiatric disorders. Frontiers in Neuroendocrinology. 214 Retrieved 13/8/2018

  8. Williams, Shawna. (03/2018). The Transgender Brain. The Scientist. 27. Retrieved 12/8/2018.

Lasya Kambhampati

Lasya Kambhampati

Lasya is a senior at Blue Valley North. She is planning on majoring in neuroscience or biomedical engineering. She first got involved in the IYNA after participating (and placing 7th) at the National Brain Bee. She is now the Director of Chapters and is focusing on helping extend the impact the IYNA has. Lasya also runs a neuroscience blog to help students prepare for the Brain Bee and just learn more about the nervous system. She hopes to help students of all ages and backgrounds learn about the amazing organ that runs our whole lives. In the future, Lasya hopes to be a neurosurgeon and research the molecular mechanisms behind memory. Outside of neuroscience-related activities, she loves to write, read, and play the violin/piano.