Is It Important to Consider Sex and Gender in Neurocognitive Studies?

Abstract

Is it important to consider sex and gender in neurocognitive, neurobiological, and clinical studies? I refer here to “sex” as a biological variable related mainly to sex chromosomes and sex steroid hormones, while “gender” stands for a psychosociocultural construct related to gender role socialization, levels of masculinity and femininity, and stress related to adhesion to gender stereotypes. It is a rhetorical question and I hope that an overwhelming majority of readers would answer: “yes, of course!” However, despite the fact that more attention has been devoted over the past decade to delineating differences between men and women in their neuroanatomy, neurophysiology, and cognitive and emotional processing (1, 2), a substantial number of researchers (basic and clinical) continue ignoring “the second sex” and study exclusively males. The reasons are multiple and range from an unawareness, through a lack of sufficient funding to examine both sexes, to the argument that the studies, to date, have not found any significant sex differences in a given paradigm or disorder and therefore there is no need to include both males and females in a study. Finally, there is a group of theorists who sees this line of inquiry (i.e., investigating sex differences in the brain and cognition) as inherently biased, thus contributing to some harmful stereotypes that may lead to increasing gender inequalities [e.g., Ref. (3, 4)]. It is hard to argue with the lack of funds and indeed there are cognitive and clinical domains where we have not seen any indication of potential sex or gender differences. Nevertheless, our technology has improved and we possess more sensitive instrumentation, which may detect subtle differences that were not previously apparent. Moreover, we must remember that men and women of today are different from men and women of two or three decades ago. We are not only socialized differently, due to changed family values and education, more competitive job market and prominence of social media, but also exposed to more environmental toxins, including endocrine disruptors, which may affect our physical and mental health (5, 6). As to the harmful effects of some studies of the neurobiological and cognitive sex differences, I agree that data are sometimes interpreted in a biased manner and may contribute to propagation of damaging gender stereotypes. However, I also believe that excluding women is much more dangerous. We have seen the harm done with several drugs released for treatment of various disorders without proper testing or consideration of women’s physiology (e.g., Posicor, approved for the treatment of hypertension and angina, slowed or stopped the heart rate especially in elderly women; antihistamines such as Seldane and Hismanal induced cardiac arrhythmias disproportionally more frequently in women), but thankfully the situation is changing (7, 8). While it is true that men and women are much more alike than different and it actually makes more sense to talk about sex and gender similarities (be it in brain structure or cognitive function), there are those subtle differences that may provide clues to disentangling etiology of some neurological and neuropsychiatric disorders, such as multiple sclerosis, autism, mood, and anxiety disorders, or shed a new light on treatment of these conditions. In short, “vive la similarite, but let’s explore differences!” I would like to use two clinical examples that I am most familiar with, to illustrate my point – schizophrenia and drug addiction.