Despite the prevalence of mental illness in today’s society, many people struggle to find a method of treatment that works for them. However, for others, a pill every night is enough to ease their day-to-day functioning. Why is this?

A recent study, led by Helen Wong from Institute for Behavioral Genetics, University of Colorado, suggests that protein kinase, AKT, and biological sex may play a role. This study was published in the journal eLife on December 16, 2020.

“The ultimate goal is to find the kink in the armor of mental illness—the proteins in the brain that we can specifically target without impacting other organs and causing side effects,” Charles Hoeffer, an assistant professor at the Institute for Behavioral Genetics, told ScienceDaily. “Personalization is also key. We need to stop hitting every mental illness with the same hammer.”

AKT may play a role in certain mental illnesses, such as autism, schizophrenia, and post-traumatic stress disorder (PTSD). This protein exists in three forms: AKT1, AKT2, and AKT3. AKT1 and AKT2 seem to be important for learning and memory, while AKT3 seems to be important for the brain’s growth and development. AKT2 is found only in astroglia, star-shaped brain cells, and may be related to brain cancer.

“These subtle differences could be really important if you wanted to personalize treatments for people,” explains Marissa Ehringer, an associate professor who worked with Hoeffer on part of the research.

Several medications, such as antidepressants and mood stabilizers, alter AKT’s activity. AKT is also involved with synaptic plasticity: the ability of the brain to strengthen neural connections in response to an experience.

“Let’s say you see a shark and you’re scared and your brain wants to form a memory. You have to make new proteins to encode that memory,” explains Hoeffer.

This study examined how male and female mice responded to the loss of various forms of AKT. Male mice without normal AKT1 had a harder time replacing older memories than male mice with normal AKT1. For female mice, this was not a problem. Males without normal AKT1 also experienced slightly more anxiety-like behaviours than males with normal AKT1. Again, for females this was not a problem. 

“We found the difference between males and females to be so great it became the focus of our work,” says Hoeffer. “It was like night and day.”

Hoeffer suspects that other proteins in the brain may function similarly and may also function differently in males and females. This is important because throughout history many scientific experiments and clinical trials have only examined males. According to an article from The New York Times, researchers often avoided using females for experiments due to the impact of fluctuating hormonal and reproductive cycles: “Name a new drug or treatment, and odds are researchers know far more about its effect on men than on women.”

Hoeffer acknowledges the need to be aware of sex-specific differences when treating mental illness: “To help more people suffering from mental illness we need much more knowledge about the difference between male and female brains and how they could be treated differently. This study is an important step in that direction.”

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