Deciphering mental illness and supporting women in medicine and science

Neuropsychiatric illnesses are mental disorders which include schizophrenia, bipolar disorder, and major depressive disorder. These illnesses are rooted in identifiable problems within the brain. They are complex conditions whose origins aren’t well-understood, and they are a leading cause of disability in the United States. Physician-scientist Dr. Amelia Gallitano is the Director of Women in Medicine and Science at the UArizona College of Medicine - Phoenix, as well as a professor of basic medical sciences, psychiatry, and neuroscience, and is a member of the BIO5 Institute. She’s a board-certified psychiatrist who studies how the environment interacts with genes to influence risk for neuropsychiatric illnesses.

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You're both a psychiatry specialist and a researcher - what led you to this dual career path?

I got interested in this path back in high school. I have always been curious about what makes people tick. My personal feeling is that that period of adolescence in high school is a really difficult time in life when you have so many things to deal with. In this emotionally challenging time, you're dealing with issues of independence from your family and your parents versus meeting other people, and it's definitely a period of angst and anxiety about how I fit in socially.

I was seeing a lot of this in my friends and myself, and I was just really curious about what caused that and what I could do to help make this challenging period of life easier for people, so I really wanted to do something about that in my career.

At the same time, I was taking AP Biology in my junior year of high school, and I remember when we studied the brain - this was still very early on when we didn't know that much, not nearly what we know now, and we hadn't even invented the term neuroscience yet. I read an article in a science publication for the lay audience about sleep and dreaming. In it, the author of the article hypothesized that the content of your dreams might be influenced by the body's physical state. 

For example, often in a dream something scary happens and you need to run away, and suddenly you're frozen and you can't move. Well, it turns out that the body is actually in a state of paralysis during REM sleep, which is evolutionarily beneficial because we don't get up and act out our dreams. 

They were hypothesizing maybe this experience in your dreams has something to do with that, and I thought, “Wow, that is really cool that something like your dreams or thoughts or emotions are actually a product of what's happening of physical substance in the brain.”

That was the beginning of my wonder and curiosity about how what is in the brain creates things like our thoughts and our emotions and creativity.
 

At what point did you consider being both a researcher and a clinician? 

I had ideas about both starting way back then.

I chose where I went to college because I knew I would have the opportunity to get involved in research as an undergraduate. There were people in the Department of Behavioral Science that studied biopsychology, and that's what I wanted to do. By the end of college, I had to make this decision - do I want to do something to help patients?

My father was a physician, and he was a huge inspiration for me in life. I still had this desire to help people that were suffering from mental illness or even just the normal anxieties and angst that we all can experience. Yet I also really loved trying to understand what was going on in the brain and the whole process of research, so it was at the end of medical school that I decided to apply to MD/PhD programs to keep open the option of doing both with my career.
 

Can you tell us about some of your current research projects?

I have a basic science laboratory, and we study the role of a certain family of genes that are activated in the brain in response to events that happen in the outside world - environmental events. These genes are the first ones to be turned on in neurons in response to events like stress, but even just events like our interaction today. These genes play an important role in those processes of synaptic plasticity and memory formation. 

I had hypothesized that because these genes are at this nexus between what's going on in the outside world and long-term changes in the brain that have been implicated in risk for mental illnesses, these genes could potentially play a role mediating the genetic and environmental contributions to risk for mental illness.

Mental illnesses aren't caused by genes alone or by just environment - it's both factors - and we still don't understand how those two predispositions or risk factors interact to result in the symptoms of mental illness, but we're learning more about it all the time.

We have basic science projects that are focused on trying to identify what genes are regulated downstream of these genes that I study. This family of genes act as something called transcription factors, which means that the proteins that they encode bind to DNA and turn on and off other genes. So, if indeed they play a critical role in translating environmental events into changes in the brain, then the genes that they are regulating must be playing important roles in that next step of turning these processes into changes in the brain that represent memory, for example.

We've used a number of different methods and identified one downstream target of the family of genes we study - the serotonin 2A receptor. We recently had a publication on that which we're really excited about. What we found was that an environmental stimulus - sleep deprivation of a mouse for 6 hours - can up regulate expression of the serotonin 2A receptor in the brain, both at the mRNA level and at the protein level. This is really exciting because that's much faster than we would have predicted for just a physiologic stimulus, something that we can all experience when we stay up late writing a paper, watching you know a movie, or when we travel internationally.

Why is this important? This receptor is the site of action of psychedelic drugs which change perception. Psilocybin in particular is being investigated as a potential therapeutic to enhance other types of therapy to treat a range of mental illnesses.

A second part of our research focus is on human clinical studies - we call this translational research, where we've taken our findings from our basic science studies and translated them to humans. We now have an ongoing clinical trial to test what we hope may become a biologically based test to diagnose schizophrenia. We're excited about that because right now we don't have any biomarkers for any mental illness - we have to diagnose them simply based on a patient's report of symptoms that they're having.
 

How does your experience as a psychiatrist influence or benefit your research?

I can point to the first time that that happened for me, and that was when I was doing studies as a postdoc on animals that were missing one of these genes that I talked about in this family of immediate early gene transcription factors. The gene that we mostly studied is one called EG3 - early growth response three. I had hypothesized that ERG3 and other genes in the family could be playing a role in risk for mental illnesses.

We had studied the behavior of the animals and found that they had abnormal behaviors that were similar to other animal models of psychiatric illness. Then we wanted to see if we could reverse that by treating the animals with an antipsychotic. What I saw was that the wildtype (healthy) animals got very sedated when we gave them a medication (clozapine), whereas the animals that lacked ERG3 were walking around the cage, and you couldn't tell which one got drugged and which one got vehicle. In contrast, the wildtype animals just were completely immobile and looked like they weren't even alive.

I thought this is really interesting because we see something similar in patients that come into the emergency room in an acute episode of psychosis where they can tolerate very high doses of antipsychotic medications that when given to people that don't have schizophrenia cause them to become politically sedated similar to what we were seeing the animals.

That's when I realized, “Wow, if I didn't have my clinical training and hadn't seen this in my treatment of patients in the emergency room and in psychiatry, I don't think I would have known.” 

This isn't a finding that you see published in papers, it's more just clinical observation so, that was the first time that I realized that my clinical training really made me recognize something in my science, and now that has formed the basis of this clinical translational study that I told you about where we hope to develop a diagnostic.
 

You were the keynote speaker for the 2020 BIO5 Inspiring Women in STEM event, and you’re Director of Women in Medicine & Science at the College of Medicine in Phoenix. Talk to us about your passion for supporting women in medicine and science.

I was inspired and really benefited tremendously from a similar group when I was doing my postdoctoral research at Washington University in St. Louis. They have a group called the Academic Women's Network, and they sponsored lots of functions and talks and networking events where I met people that were really inspirational to me. I learned a lot and got a lot of guidance.

One of the very tangible things that they did was they worked together with Washington University in St. Louis to do a faculty salaries study while I was there. At one point, early on in my postdoc, I suddenly got a very substantial raise that I didn't ask for and I hadn't expected.

Was this impactful? Absolutely! When I was finishing my postdoc and applying for jobs, I got a job offer, and the chairman of the department that was offering me the job was telling me how he really liked to pay people at a very high rate, but when he gave me the offer, it was lower than what I was already making at that point. If I hadn't had this experience of having this raise I would never have known that I could ask for more.

That's an area where there is this huge discrepancy in salaries that persists today in medicine. The AAMC (American Association of Medical Colleges) has just put out a report in October of 2021 saying women remain substantially underpaid compared to men in the fields of medicine and science. It's still a huge problem.

The AAMC has tremendously supported women in medicine and science programs. In fact, they encouraged medical schools to start these kinds of programs, and their studies like this one offer recommendations for promising practices to attain faculty salary equity. Women continue to be paid less than men for all kinds of jobs, and this is after you control for other factors like productivity, and women of color paid even less than white women, so it continues to be a major problem.

How did it help me by having a higher salary? I was able to pay for childcare for my children and that allowed me to succeed in my job because I could work longer hours, and I could put in the work that was necessary to accomplish what I needed to get tenure, get grants, and to succeed in my career, so I’m very committed to enabling other women to have those benefits as well. We need it if we're going to succeed.
 

What is your biggest piece of advice for young girls who might want to pursue a career in science or medicine?

Follow your passion. Don't do things because you think you should or because somebody tells you you should. Figure out what you really love, what gives you energy, what makes you excited when you get up in the morning, and if it's science and medicine, that’s fantastic.

But it's a long haul. It's a lot of work, and you will encounter obstacles. You can get over all of those if this is what you really love and if it gives you energy.

Don't be afraid to ask for things and to ask for help.

I have the personality that I think, “Oh, I can do it myself. I don't need anybody to help me.”

You can't do it yourself, and you don't need to. We benefit so much from interacting with others from having a network. You learn so much from other people, so let them help you. You know what? Then you will be stronger, and you will be in a better place to turn around and help them back when they need it.

That's why something like Women in Medicine and Science has been so great, because it is a place to bring together women have similar experience, and you can do exactly that - you can be there for each other, whether that's advice on a rejected grant submission, or if you and your partner are traveling and you need childcare. 

I do want to also mention, because often when we talk about women, we talk about childcare, not everybody chooses to have children. But even my colleagues that don't have children, they have parents or aunts and uncles that they need to be cared for. Another very common thing for women in professional careers is that they may have a significant other that doesn't have a job opportunity in the same city. Then, they need to be able to afford a second home or second apartment and to be able to fly between two different cities.

Even if you haven't chosen to have children, you still may have challenges that your male colleagues may not have.
 

We love to think of our researchers and clinicians as superheroes. If you were a superhero, what would your superpower be?

I think my superpower would be to inspire others.

I think that it's so important because having somebody believe in you is critical for your success, so the ability to inspire somebody and say, “You can do this, you need to believe in yourself, I believe in you. If you have questions, I am here, and I believe you can do it,” that can give them the power to go on. 

I like to do this, even in lab meetings and for my lab. We have trainees, all the way from high school students that come in to do internships, undergraduate and graduate students and postdoctoral trainees, all the way through the different levels. Even if you are brand new volunteer in the lab and you're just doing what may seem like a very mundane task of pipetting or genotyping animals, for example, I like to talk about how important that particular task is - how it fits into the larger experiment and how that experiment fits into the whole project, and what the implications are of that project for things like people with mental illness.

I like to inspire people to understand the context of what they're doing and tell them why they're doing it. Then they get excited, and they realize they're part of the team and they're making an impact, even if it's a small step. That's the way you get started, and it requires all those steps to accomplish these larger goals.

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