The National Insitutes of Health instituted a new requirement for inclusion of sex as a biological variable in animal research in 2015. This policy change, along with earlier directives for inclusion of women in clinical studies, has resulted in a dramatic increase in our appreciation of sex differences across many disease states. Neurological and psychiatric disorders are among those most impacted. While there have been many studies over the years reporting subtle differences between men and women with respect to clinical features and treatment responses of several neuropsychiatric syndromes, our understanding of the biological underpinnings of such differences has advanced only recently with the advent of unbiased genome-wide data. Increasing evidence is now suggesting fundamental differences in transcriptomic abnormalities that occur in the brains of men versus women with a variety of brain disorders. There are also evolving data showing that genome-sequence variations influence disease risk in a sex-specific manner.
In 2010, the National Academies’ Forum on Neuroscience and Nervous System Disorders hosted a workshop titled Sex Differences and Implications for Translational Neuroscience Research, which outlined the public health importance of studying sex differences in the nervous system, discussed when sex differences should and should not be considered in research, and considered how to design studies that evaluate sex differences. Over the past decade, the field has progressed significantly, as described above. Therefore, it is timely to revisit this topic, take stock of progress and new challenges, and identify future opportunities and potential directions.
On September 23, 2020, the Forum on Neuroscience and Nervous System Disorders hosted a virtual public workshop that brought together experts and key stakeholders from academia, government, industry, and non-profit organizations to explore emerging evidence regarding differences in transcriptomic abnormalities that occur in the brains of men versus women with a variety of brain disorders including depression, post-traumatic stress disorder, drug addiction, neurodegenerative conditions, and other brain disorders.
Invited presentations and discussions were designed to:
- Review the landscape of emerging evidence regarding sex differences in transcriptomic abnormalities in a variety of brain disorders, and discuss how this can be used to advance understanding of brain disorder pathophysiology.
- Explore ramifications for therapeutic development for these disorders, including identification of new targets, implications for preclinical and clinical study design, regulatory considerations, and potential sex-specific treatments.
- Discuss open research questions and opportunities to move the field forward.