- Are there any sex differences, male-female differences in sort of these dopamine levels, working memory, injuries, concussion, like things that would direct people toward different routes of treatment given that, you know, maybe there's more susceptibility in one case, maybe less susceptibility, maybe certain neurotransmitters are more effective in improving symptoms in men versus women.

Do you see that in the clinic? - Yeah, that's a great question. There was Emily Jacobs, who's a professor at UC Santa Barbara now in the psychology department, when she was a graduate student in my lab, studied the role of estrogen on working memory and dopaminergic function. And what she brought to my attention at the time, and it was embarrassing that I didn't know, was that the frontal lobes are full of estrogen receptors.

There's probably more estrogen receptors in the frontal lobes than any other part of the brain. - In men and women. - Estrogen boosts dopamine. So higher estrogen levels correlates with increased dopamine levels. And there was some anecdotal evidence that in postmenopausal women who were put on estrogen that their working memory improved, and there was a kind of evolving link between estrogen and frontal lobe function.

She did this amazing study where she studied healthy Berkeley undergraduates at two points in time during their menstrual cycle when estrogen was at its lowest and what was its highest, and she also genotyped them for this enzyme they were talking about to know if they were sort of lower or higher on the dopamine level, and then put them in the scanner and measured frontal lobe function, and showed that there was a clear, the frontal lobe function was modulated by where they were in their estrogen cycle.

When they were low estrogen, they were low dopamine, and if they were low estrogen and low dopamine to start, they really had decreased frontal lobe function and decreased working memory ability. So it fluctuated based on this interaction between estrogen and dopamine, suggesting that not only is dopamine important, but hormones are clearly important, and they work synergistically.

So as we're developing this cocktail, we certainly have to bring hormones into the equation and learn more about it. There's just so little information about hormones and cognition. - Yeah, one of the themes that's come out of some of the episodes we've done with MDs who specialize in endocrine health is that for both men and for women, optimizing estrogen levels is really important for cognition and vascular function.

I think people mistakenly hear, okay, testosterone, men, estrogen, women, obviously both hormones are present in men and women. In fact, I think, I know that testosterone levels in women are actually higher than their estrogen levels when you sort of use the same units of measure. It just so happens that they still have lower testosterone on average than the typical male, but that men whose estrogen levels are too low suffer cognitive defects and vascular defects.

So this idea that more testosterone, lower estrogen in men is the ideal, and it just doesn't hold, it doesn't hold. I mean, unless you want to be dumb and have a heart attack, it just doesn't hold, very interesting. Do we know what estrogen is doing there? Is it, it's specifically raising dopamine.

We don't have to get into the synaptic biology, but it's so interesting. - Yeah, it's actually boosting dopamine activity. - So it's making more dopamine available. - Yeah, yeah, it's really amazing. And to think about it sort of fluctuating, certainly during the menstrual cycle, we can think about how much it fluctuates in an individual woman over 30 days, but then you can think across individuals, you can think about how much it can account for individual differences.

So not only sort of knowing your dopamine level, but just knowing sort of estrogen and serotonin is really going to be important. - Interesting. (upbeat music) (upbeat music) (upbeat music)