Does Your Brain Reflect Your Gender? — Harvard Gazette

Jill Goldstein The clinical neuroscientist, Harvard Medical School professor, and founder and executive director of the Center for Gender-Specific Innovation at Massachusetts General Hospital shared what science has revealed about sex-specific differences in the brain.

When talking about sex differences in the brain, there are a few things to keep in mind.

First, sex and gender are different. Gender is based on biology – the effects of sex chromosomes and gonadal hormones on the brain and body – while gender refers to an individual’s social roles and behaviors. Second, there are many opinions about sex differences, and these can be informed by many factors. The science on sex differences in the brain is based on strong evidence that goes back decades. On the other hand, differences in public opinion can go back even further. At the time, in the 1960s, there was a lot of debate about women’s roles in the workplace and other fields, and there was concern that research on sex differences in the brain would suggest that men were better. Ironically, it turns out that women’s brains are more robust in many ways. However, this mindset creates unnecessary and false competition, leads to anti-intellectual thinking and the omission of important aspects of the conversation, especially when it comes to health, wellness, and disease research.

So are male and female brains different? The short answer is that they are. This difference begins during fetal development early in the second trimester. Sex chromosomes (whether the fetus has XY (male), XX (female), or some variation of these) and gonadal hormones drive the coordination of sex differences in body and brain development. The so-called organizational influence of hormones on the brain is retained throughout life, but there is a lot of variation in what, for lack of a better word, could be called brain sexual dimorphism. That is, despite the use of the term sexual dimorphism to indicate certain differences, no one who studies the biology of brain sex believes that there could only be two forms of sex.

While organizational influences of hormones lay the foundation for fetal development and puberty, environmental exposures influence biological expression, even if some fundamental biological differences are determined during early development. This results in greater brain diversity within the sexes than between the sexes; that is, there is greater variation within women and within men than there is between men and women. However, it is these small brain differences that may have important implications for why we see sex differences in almost every brain disease we know of, for example, depression, anxiety disorders, substance use disorders, schizophrenia, autism, and Alzheimer's disease. Sex differences in the brain also vary depending on the timing across the lifespan. For example, sex differences emerge when gonadal hormones are differentially released into the brain and body, as during fetal development, puberty, and pregnancy, or when gonadal hormones are depleted during menopause compared to men of the same age. These natural reproductive stages provide important opportunities for understanding why and how we see sex differences in the onset, prognosis, and course of many diseases that may lead to differences in treatment responses.

The same woman may have brain regions activated differently at different times during her menstrual cycle. The so-called activation effect of gonadal hormones indicates that the brain works differently under different hormonal changes. Depending on when men and women are compared in a study, this may affect the study results. However, these differences in brain activity do not necessarily translate into differences in behavior. Sex differences in brain activity may produce similar behavior in women and men. For example, when a woman is in a certain phase of her menstrual cycle, hormones may have a different effect on her brain activity, but her behavior and task performance may not change at all. This difference is one of the reasons why studying sex differences in the brain can be complicated. However, knowledge about sex differences in the brain allows us to take these differences into account in the design of studies.

Indeed, there is a reason why it is so important to continue to study and distinguish sex differences in the brain from gender differences: many chronic diseases and disorders affect men and women differently. Could a deeper understanding of the role of the brain, including sex differences, lead to more effective treatments and save lives?

There is still much to learn. The brain is a multifunctional organ that is constantly changing throughout life. Understanding the biology of the brain is essential to develop more effective diagnostic tools and treatments, especially those that take into account gender influences, leading to precision medicine.

—Interview by Anna Lamb/Harvard University Staff Writer

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