Lara is assistant professor of Neuroscience at the University of Leiden, and in November 2022 she co-organized the workshop “Rethinking sex in neuroscience of mental health” together with Marieke Bos (Leiden University), Amber Ruigrok (University of Manchester), and Christian Tammes (University of Oslo).
Lara, can you tell us a bit about your research field, and how you got into it?
I'm a neuroscientist studying brain development. There are sex and gender differences in almost all psychiatric disorders in terms of how frequently they are diagnosed, but also in how symptoms are expressed. And currently, we don't understand well why these differences are there. Sex and gender are challenging to disentangle in research designs including humans. With sex, we refer to biological pathways including chromosomes, hormones, immune system, anatomy. Gender on the other hand is a multifaceted term: it may refer to gender identity, but also to social roles, expectations and norms, which also cisgender people experience. Disentangling the effect of sex and social context aspects of gender in the brain is the focus of my work.
During my PhD research on ADHD and autism, I thought that sex differences were a problem in my research design due to the fact that clinical samples had more male than female participants. But when I looked more closely into the reasons behind these differences, I encountered lots of leading theories that I was unable to replicate. I found that research was very limited on this topic, which can reinforce gender stereotypes and inequalities. For example, females are often underdiagnosed with autism and ADHD, making it harder to recruit them for clinical studies. As a result, we have less knowledge on how these conditions may be expressed differently in females. Females have been historically ignored for a long time in medical research, and a lot of relevant questions have not been asked. There is a lot of work that needs to be done in this field, and a lot of expertise needed in society to bridge this gap.
How easy it is to understand whether sex differences are related to biological factors, or to the cultural context we are raised in?
It is actually very challenging! One of the things I'm doing is to look at the social cultural influences to see whether within each sex what individual beliefs people have about gender, the gender stereotypes they're exposed to, how gender stereotyped their feelings and behaviour are, as well as online social media exposure. If we see variation within sex, we may assume that there might be some kind of relation with these differences in beliefs. You can also look across countries where you have different gender inequalities. There are, for example, shocking findings that in countries with higher gender inequality there are larger sex differences observed in the brain. So, not all the biological differences observed have a biological origin.
On the other hand, we also look at biological mechanisms. We study hormones that are not often described in literature. Testosterone is the main one if you investigate the research on sex, but we also look at DHEA and estrogens to see what the effects are during puberty. Finally, we investigate effects of the X chromosome on the brain, also in indirect ways. By making clever use of data, indirect modeling, and statistics, you can still show what the effects of these different pathways are on sex-related differences.
Moving to the workshop: how did you get the idea of organizing this Lorentz Center workshop, now four years ago?
Back then, I was trying to plan my next step in the field. I had research ideas, but I also thought: hey, there are so many brilliant people working on this, but why is this going so slow? Why don't we see implementations of this in the clinical fields or in society? Why is this so difficult?
I decided to take a step back and evaluate this. This research field is extremely interdisciplinary: you need to know things about hormones, you need to know things about the patients, you need to know things about genetics, about the social constructs, about all these different methods that we have and the way to analyze them. There's no single person who can know everything. I thought it would be very important to come together with people from all these experts from different fields, to learn from each other and see whether we can collectively address the question: what do we all need to do to move this field forward and give it a boost?
And a Lorentz workshop is the perfect thing to do that. We were locking ourselves up for five days, discussing this. What I found amazing is that we had a list of people we really wanted to have there, and everyone said, within a day: “Yes, I will be there”. They emptied their agenda for the full week and were present. And that already highlighted how important this topic is to people, I think.
Did what happen during the workshop match your initial expectations?
I initially thought that I would leave the workshop equipped with new technical and methodological knowledge, new fancy analysis techniques that I could apply to my research. But during the week, I learned so much and it also shifted how I want to fill my career. It really had a significant effect on my career choices.
In fact, after two days of discussing with all these people different kinds of aspects at some point someone said: “When you talk about gender, I feel like you mean something completely different than how we talk about it in my field. And the same for sex.”
They seem like very simple terms, but we all used them in different ways, so how can we interpret findings from different research studies?
We found out that in many papers the methods that are used to identify sex or gender were so different that we cannot draw meaningful conclusions. Even when you include just binary sex, if you don't set up the research design or statistical analysis in a good way – mostly because of a lack of training - the conclusions are worth nothing.
This of course needs to be updated: we first need to define the concepts, then we need to be able to measure it. During the workshop, we decided to develop a roadmap paper with hands-on advice on how to design a new study to make sure it is reproducible and reusable. We wanted to make the advice very hands-on and practical, but we felt these small things could make a big change in this field.
We also recorded a podcast during the week because we wanted to share the whole process and the way we started rethinking about sex and gender in this field.
It was something so wonderful to do. It was exhausting because we did that after a whole day of talking and thinking. But it was so worth it. And it helps make the field transparent and open and accessible to a wider audience.
And next to these very tangible outcomes, what happened to the participants of the workshop?
The whole workshop was such a warm bath. Even though it's a couple of years ago, we all still talk to each other. There were many cross collaborations that came out of it. We all see each other still at conferences, get invitations for conferences, support each other, which is so necessary in this field. We built connections for a lifetime. And that was really facilitated by the Lorentz Center.
Lara, you are also very involved in sharing your research with a broader public, as you did with your popular science book “Atlas van ons brein”. Before we say goodbye: is there something you feel should be more widely known about your research field?
There are many misconceptions about sex differences which feed into policies and into the way we live today. You see that, for example, with the upcoming Manosphere voices and how they affect how youth and young people act in the classroom and with peers, but also to their teachers. Most of these ideas start with a seed on assumptions on neuroscience. They start with differences in how male and female brains are different. And that is used to justify social constructs. For example, they use neuroscience to claim females are more caretaking and therefore they have to stay at home with the kids and males are better in decision making, competition and therefore they need to have more leading roles. But if you look at the research on brain and behavior, this link is simply not there. It's very, very harmful that these conclusions are drawn and I would really like to advocate for a retake on how we look at sex differences.
At the same time, there are true differences in the brains between males and females, but the way these results are interpreted are not justifying our social systems. The danger is that a lot of researchers pull back from doing research on this topic because they are scared that their work will be misinterpreted. And this is harmful because we still lack a lot of knowledge to ensure people are treated in the right way now or diagnosed in the right way, as in the case of ADHD and autism.
This is such an important topic, I would also like to encourage people to keep on talking about this to the public. And if they need help with that or want to talk to me about anything related to this, they are very welcome to contact me!
Lara Wierenga
Interview written and edited by Federica Burla
