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We are glad that our paper (1) raised discussions on the relations between sex and the brain and on our new methodological approach. Clearly, sex affects the brain, as evidenced in differences between brains from females and brains from males in both macroscopic and microscopic features. However, the fact that sex affects the brain does not necessarily entail that there are two distinct types of brains, “male brains” and “female brains,” as there are two distinct types of genitalia (2⇓–4). Answering this question was the aim of our study. The rational for our method of analysis was derived from animal studies demonstrating that in contrast to sex effects on genital organs, sex effects on brain features may be opposite under different environmental conditions. That is, what is typical in one sex category (e.g., females) under some conditions may be typical in the other sex category under other conditions (reviewed in refs. 2 and 3). As a result, brains are expected to be composed of both features more common in males compared with females and features more common in females compared with males, a situation that rarely occurs in genitalia. When it does occur, the genitalia are classified as “intersex” and not as “male” or “female” (5). Our analysis was designed to assess how common this “mixture” of features is in the human brain. We found that there are many more “substantially variable” brains, that is, brains with both features that are more common in males compared with females (“male-end” features) and features more common in females compared with males (“female-end” features), than “internally consistent” brains, that is, brains with only “male-end” or only “female-end” features. The finding that substantial variability is more prevalent than internal consistency was robust across different samples, age groups, type of magnetic resonance …

Reply to Del Giudice et al., Chekroud et al., and Rosenblatt: Do brains of females and males belong to two distinct populations?