Adolescence is a time of profound change – a time of self-discovery and transition that is both exciting and challenging. These changes can be attributed in part to the hormones that start circulating at this age, which, in addition to leading to the expression of secondary sex characteristics, trigger a shift in brain development. It is also a time when many individuals might start to experience mental health challenges, especially more vulnerable groups, such as LGBTQIA2+ youth.

One subset of this group, namely individuals experiencing gender dysphoria, are particularly susceptible to the effect of hormones on the brain. Gender dysphoria is a medical diagnosis listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), a manual published by the American Psychiatric Association to diagnose mental health challenges.

At adolescence, these individuals often either take hormone blockers to delay the onset of secondary sex characteristics and/or undergo hormone therapy to begin expressing the characteristics of the other gender, but little research has been done on the effect of blockers or hormones on brain development. And, although research has been done exploring the brain basis of mental health conditions, relatively little work has been done on how hormone therapy could affect the relevant brain areas.

This is the area of research that Dr. Malvina Skorska chose to focus on throughout her post-doctoral studies. With help from her Brain Canada – Kids Brain Health Network Training Award, she recruited youth experiencing gender dysphoria and their cisgender peers to participate in a study involving Magnetic Resonance Imaging (MRI), a neuroimaging technique that allows researchers to look at brain structure and function. By taking images of their brains at different stages of hormone therapy and comparing it to their peers, Dr. Skorska examines how various hormones affect brain development but also whether the brain changes as the secondary sex characteristics of the other gender start to be expressed.

During the Brain Canada-Kids Brain Health Network funded postdoctoral fellowship, Dr. Skorska received training on analyzing aspects of brain structure, taking the lead on a study examining cortical thickness, cortical surface area, and T1 relaxation time (which generally reflects the underlying tissue density) in a sample of adolescents assigned-female-at-birth who experience gender dysphoria (GD AFAB), cisgender (i.e., experienced gender and sex assigned at birth align) girls, and cisgender boys. The GD AFAB participants were not receiving puberty blockers or hormone therapy. Dr. Skorska and her team also examined the brain features in relation to the participants’ sexual orientation and age. They found sex assigned at birth differences when examining group differences, mainly reflected in surface area (cisgender boys > GD AFAB and cisgender girls). In the context of sexual orientation and age, however, they found that cortical structure of cisgender boys and GD AFAB was similar, and this was reflected mostly in shorter T1 (i.e., denser, macromolecule-rich tissue).

The findings included some support for the idea that the cortical structure of GD AFAB adolescents aligns with the experienced gender, but in the context of age-related changes in sexual attractions during adolescence.

The findings generally highlight the importance of age-related changes in brain structure, examining brain structure in adolescence, including more subtle indices of the underlying tissue, and the inclusion of sexual orientation in studies of brain development, including in studies of GD.

More generally, this work will improve our overall understanding of how the brain develops in adolescence. Beyond advancing scientific knowledge, this project is also proving to be quite empowering for the youth who participate in the study, many of whom are enjoying the opportunity to contribute to answering questions about what gender dysphoria is and how it might be reflected in the brain.

Receiving the training award also helped Dr. Skorska expand her own scientific knowledge: “I had a really great experience and was very grateful and fortunate to receive my post-doctoral fellowship from Brain Canada,” she said. “Before I started working on this project, I didn’t have a lot of neuroscience training and having this opportunity allowed me to gain some very important training on neuroimaging and how to process the images that we receive.”

In addition to learning neuroimaging acquisition, processing and analysis skills, Dr. Skorska learned about clinical research, research ethics in a clinical setting, collaborations with a large group of individuals with expertise in specialized areas, grant writing, and how to write and speak about neuroscience research for both academic and non-academic audiences. She attended webinars about knowledge translation tools and building a career portfolio and learned about family engagement in research in a course offered through this fellowship.

Since gaining valuable neuroscience skills over the two-year term of her grant, she was able to leverage knowledge gained throughout her fellowship into a CIHR postdoctoral award. This new funding will continue to support her work on gender dysphoria, while allowing her to delve more deeply into brain function by incorporating some cognitive and behavioural experiments into her research and exploring different ways to analyze and understand brain images, as new software packages and techniques are always appearing in the constantly evolving field of neuroimaging.

“With this support, I learned many useful skills beyond neuroimaging methods that will be beneficial to me throughout my career.”

Eventually, Dr. Skorska hopes that her work can help bridge the gap between mental health interventions and neuroscience research. Exploring whether the function of brain areas that are known to correlate with depression or suicidality is affected could potentially enable the use of targeted therapies to try to minimize and help with experiences of mental health challenges. This would lead to better support for youth experiencing gender dysphoria during a critical time in their development and would, ultimately, help improve their quality of life.

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