Sex and gender are crucial variables in understanding brain development and disease. Biological sex is determined by genetic and hormonal factors, whereas gender is a multidimensional construct shaped by social and cultural influences. The interplay of these factors contributes to sex-specific susceptibilities and disease progression in psychiatric and neurological disorders. However, sex and gender are often considered as a single variable, which can lead to biased data analysis and interpretation. This commentary aims to analyze how sex and gender influence brain structure and function, with implications for personalized medicine, research, and the development of gender-sensitive clinical guidelines. Findings from various studies employing neuroimaging techniques and animal models are discussed, as well as the impact of biological sex, gender, environmental, cultural, and social factors on brain development, organization, and behavior. Evidence suggests that sex differences in brain structure and function are not only genetically determined but arealso influenced by gender-related experiences and societal contexts. Importantly, discrepancies between male and female brains are reduced in gender-equal societies. Preclinical studies play a pivotal role in determining the influence of biological sex, independent of gender, in different disease models. The findings underscore the need to consider both sex and gender in research and clinical practice to avoid biases and promote equitable health outcomes. Moving forward, we advocate for gender-sensitive approaches to be integrated into brain research and in clinical guidelines to achieve personalized and precision medicine.
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