Sex differences and stress resistance

Professor Bruce McEwen discusses differences between the sexes in coping with stress. These are mediated by hormonal, neural, and genetic factors.

Good question. First, let’s talk about sex differences, and then let’s talk about the concept of resilience, and what happens in the brain. If we talk about sex hormones and sex differences, we know that early in development – in the human it’s at mid-gestation and it also continues around early after birth – there is the production of testosterone by the testes that causes what we call sexual differentiation of the brain. Certain brain structures from the hypothalamus to parts of the cerebral cortex, and probably a lot of other parts of the brain, are subtly changed by the testosterone, and also by genetic factors from the Y chromosome, so that the male brain develops in a somewhat different way from the female brain. At each stage the male and female are, of course, boys and girls, babies, are interacting with their environment, and processing things in somewhat different ways, so the combination of experience and these biases by the genetic and hormonal factors leads these brains to be somewhat different and to prioritize things, if you will, in different ways. The second part is that the adult brain, instead of just having the hypothalamus being the area that controls reproduction and is sensitive to sex hormones, the entire brain is, to some extent, responsive to sex hormones, and the reason for that is that there are receptors for steroid hormones that are found not just in the cell nucleus, where they regulate gene expression, but they are found in other parts of cells, in the synapses, in the dendrites, in glial cells, and they regulate not only genomic, genetic regulation of genes, but they also regulate second messenger systems, very much like neurotransmitters. We didn’t know about these receptors until we began to use high-resolution techniques, electron microscopy, to look inside cells with antibodies for these receptors. Now we realize that the entire brain responds to all classes of steroid hormones, particularly the sex hormones, and in each case, whether its cerebellum or the movement control areas of the brain or the spinal cord or the hippocampus in memory or the amygdala in fear, or areas in the brainstem involved in pain, each of these areas responds to the sex hormones. So, if we put together what happens early in life, in addition to the experiences that people have, being a good supportive family life or a chaotic home life, plus these subtle sex differences, plus then the actions of circulating hormones in adult life, you have many different possibilities for producing different outcomes and vulnerabilities. For example, women are more vulnerable to anxiety and depressive disorders, but males are much more vulnerable to substance abuse and antisocial behavior. You could argue that these are just simply different ways that the male and female, on the average, sort of acts out or projects their response to, say, a toxic stress, and that it is not so much vulnerability, but a different strategy for dealing with these conditions.