#WhyIScienceQ&A: A psychologist integrates her clinical perspectives with her research on autism and schizophrenia

Susan Kuo discusses how she centers diversity in abilities and needs in studying relationships between genetic backgrounds and individual traits across development.

By Allessandra DiCorato

March 7, 2023

Credit: Allison Dougherty, Broad Communications

It was early in her career when Susan Kuo began learning about how people experience developmental differences and mental health challenges. At the University of British Columbia as an undergraduate student, she joined labs studying brain functioning in schizophrenia, and after graduating with a bachelor’s degree in cognitive science, spent a year doing research and volunteering for a crisis and suicide hotline. Though she hadn’t initially sought out schizophrenia research, she began to connect what she was learning in the lab with experiences she’d had as a child watching her family navigate a relative’s psychiatric condition with few supports.

Kuo moved from her home in Vancouver, Canada to begin graduate work at the University of Pittsburgh, where she studied behavioral and neuroimaging genetics of schizophrenia. She completed her residency at UCLA Medical Center, focusing on working with people with schizophrenia and autistic young adults, and graduated with a PhD in clinical psychology in 2020.

Now a postdoctoral fellow advised by Elise Robinson at the Broad Institute of MIT and Harvard, Kuo studies the relationships across development between genotypes and phenotypes — genetic backgrounds and individual traits — in autism and schizophrenia. We spoke with her about her training as a clinical psychologist and how she combines that with her genetic research in this #WhyIScience Q&A.

What got you interested in psychology?

I wanted to be a doctor growing up and had always been interested in how people develop. Once I got to college, I realized psychology spoke specifically to my interests and I started working in labs studying brain functioning in people with schizophrenia. Because these labs happened to focus on schizophrenia, I started to make the link between what I was learning in the lab and my earlier family experiences.

I grew up with a relative who developed schizophrenia as a young adult. They came to live with my immediate family for a few years right after their initial psychiatric hospitalization. Although they had always been gentle and considerate, it was much harder to interact with them because they had become very guarded, and it wasn't always clear when they were going to be more engaged with us or their internal experiences.

Having immigrated to Canada only a few years before, my family didn’t know how to even begin seeking a psychiatric diagnosis and treatment and felt unable to reach out for support beyond our family due to stigma. I now know how to label these experiences and help my family better support my relative, but at the time, no one in my family knew why my relative was experiencing these unique challenges and which of their challenges were addressable. Through research, I could better understand the questions that the adults who were around me when I was growing up had few answers for. And through research, I can work on building supports for people with neuropsychiatric conditions that are tailored to different abilities and needs in their development.

What are you working on now?

Some of my initial postdoc work in the Robinson Lab and in collaboration with Mike Talkowski’s lab examined variability in the timing at which autistic children attain their early developmental milestones, and how this varies with key clinical characteristics such as having co-occurring intellectual disability or carrying a rare de novo genetic variant associated with neurodevelopmental conditions. That study emphasized going beyond the frequent characterizations of autistic people, which often use averages, as many abilities and needs across the spectrum aren’t well represented by these middle points. The study helps us recognize the tremendous diversity of early phenotypic development in autistic children, and I hope it reassures families and clinicians that there's no one timeline with which autistic children can attain developmental milestones.

That led to one of my current projects which uses some of these early developmental phenotypes and incorporates them into an early clinical stratification model. Working with Elise and other great mentors who are clinically trained scientists, including Somer Bishop (UCSF), Audrey Thurm (NIH), and Stephan Sanders (Oxford/UCSF), we're developing a publicly available resource that pediatricians and families can use to put easily accessible information about an autistic child’s early development — like age at walking — into a user-friendly online dashboard. The dashboard can then provide information about the probabilities that the child might carry a rare de novo variant associated with neurodevelopmental conditions. This tool leverages phenotypes that are often apparent by the time a child is four years old, and is just one example of how we can tailor clinical tools to specific developmental periods.

How does your research inform clinical work and vice versa?

In the clinic, I try to understand how each person experiences various abilities and needs and how these phenotypes may vary throughout their development. As in the lab, I’m learning not only about the person’s current experiences, but also how their past experiences inform my approach to supporting their future experiences. While research on genotype-phenotype relationships in neuropsychiatric conditions has largely been based on studying phenotypes that are measured at a single time point, I’m building on this foundation by also considering the timings and sequences of phenotypes unfolding across development.

I also think clinical tools are where I can bring the experiences of clinicians and the people we're working with to bear on research. For instance, the current professional guidelines in medical genetics and pediatrics are that all autistic children are recommended to get clinical genetic testing. In practice, most children do not, despite the potential of a clinical genetic diagnosis for further tailoring supports for a child. The majority of surveyed parents and caregivers of autistic children are interested in getting clinical genetic testing, but if it's not covered by medical insurance, it can cost thousands of dollars.

I hope our early clinical stratification dashboard can help bridge the gap between clinical guidelines and decision making surrounding clinical genetic testing. Having personalized information about the probabilities with which a child might carry a rare de novo variant could facilitate conversations between pediatricians and families about seeking clinical genetic testing. I'd love it if our tool could serve as a piece of evidence families could choose to support their insurance claim that a genetic test is medically necessary and should be covered.

How do you communicate your research to the general public?

When we wrote that paper on developmental variability in autism, my goal was to summarize information in ways that were accessible not only to people who regularly read medical journals, but also autistic people and their support networks. I created different data visualizations to minimize sensory overload — for example, I presented developmental variability in multiple phenotypes as a single timeline rather than many time-to-event plots. I tried to consider not only the words but also the figures we use to portray the people we’re learning about, while capturing all the statistics we’d present to a scientific audience.

Thanks to the advocacy that autistic people have been doing, there's a big push in the research community to thoughtfully bring in more stakeholder perspectives. We want to make sure that we share accessible representations of the relationships between genotypes and phenotypes by talking with families of autistic children, pediatricians, clinical geneticists, communications experts, and accessibility advocates. Together with the Autism Science Foundation, the Pattern group at Broad, and the new Neurodevelopmental Variability Initiative at Broad, we're planning to recruit advisory groups to get their opinions on the early clinical stratification dashboard we’re building, and whether the ways we're presenting the information are understandable, useful, and minimize any clinical burden that people might have.

What do you find most rewarding about your work?

I’m grateful to be part of the intellectually engaging communities in the Stanley Center at Broad and the MGH Center for Genomic Medicine. I’m always learning from the enlightening conversations I get to have with thoughtful mentors and collaborators, and I’m constantly inspired by the creativity and rigor that my colleagues bring to their work.

It’s also a privilege to work with the biggest datasets including genotyping and deep phenotyping in autism and schizophrenia, thanks to studies supported by the Simons Foundation and the Finnish SUPER study. Every data point comes from a person that I could work with in a clinical setting, and I truly appreciate how thousands of people generously shared many aspects about themselves for research. With them, we can make more nuanced inferences about why and how groups of people with different genetic backgrounds may develop diverse phenotypes. It’s rewarding to see these building blocks of knowledge — like all this information about autistic children’s development — captured in one space, and to stack these building blocks towards tailoring supports for specific developmental abilities and needs.

What advice would you give someone who wants to go into clinical psychology?

When I started my PhD, I wouldn't have thought that I'd be honing my computational skills so much, but once I realized the potential of large-scale quantitative analyses to inform supports for neuropsychiatric conditions, I was hooked. So I would say: Think about the bigger picture. Figure out who you're interested in working with, what's most important to them and why, and start to shape your understanding of scientific and clinical approaches that you can use to address those questions.

What impact do you hope your research will have?

My aim in integrating genetic and phenotypic information is to meet each person where they’re at in their development. I believe that as we become more deeply aware of the diversity in people’s abilities and needs, we’ll be better equipped to build clinical tools that are more flexible, for more people, that support them more in the ways they want to be supported.