I began studying genetics in my first year at Harvard, somewhat by accident. I had applied to be part of a seminar entitled “Chess and Mathematics,” but that course was filled, and I was bumped into “Darwin’s Finches”. I was disappointed, but not for long. I began to spend time in the archives of the Museum of Natural History, measuring the beaks of finches collected nearly 200 years ago, each with a tag tied to its leg with minute handwriting denoting the bird’s scientific name. Holding the birds that inspired the theory of evolution was the start of my fascination with genetics and classification. The next semester I moved to a synthetic biology wet lab, and after that to a drosophila lab at the Fred Hutchinson Cancer Research Center. At the same time, I was developing an interest in psychiatry and clinical psychology. My grandfather, who I idolized, was a psychiatrist. His son, who I never met, was diagnosed with schizophrenia. The family was unusually tight-knit, so my uncle’s absence was conspicuous, and highlighted how profoundly schizophrenia had impacted my father’s family of origin.
I pursued a doctorate in clinical psychology at the University of Iowa because it presented the opportunity to pursue genomics research and clinical training in psychopathology. At both Iowa and the Minneapolis Veterans Affairs Medical Center, I was able to spend time with individuals who had experienced psychosis, working on inpatient, partial hospitalization, and outpatient treatment settings. When a postdoctoral opportunity arose on the Suffolk County Project, led by Drs. Roman Kotov and Evelyn Bromet and currently the longest-running study of first-admission psychosis in the world, I was thrilled to merge my research and clinical interests. My work with the project has focused on understanding how genetic risk factors manifest longitudinally over the 35 years the study has been running. We have shown that genetic risk can indicate who is more likely to experience a more severe course of negative symptoms. With the leaders of other first-episode studies, we are developing a consortium of longitudinal studies that can definitively evaluate how genetic risk impacts the course of symptoms, cognition, function, and response to treatment in psychotic disorders.
In the past two years, I have developed an arm of research that aims to leverage what we know about the structure of psychosis to improve the power and precision of psychosis GWAS. Preliminary results from these analyses have confirmed the genetic structure of psychotic symptoms, mania, and depressive symptoms mirrors phenotypic structure, such that each genetic factor is relatively independent of the other. The support of the SIRS Early Career Award allowed me to present this work at the society’s 2022 meeting. A related line of research takes a broader approach, and tests whether transdiagnostic phenotypes of internalizing, externalizing, and psychosis, can identify more genetic risk factors than case-control GWAS. My hope is that this line of research will provide a clearer picture of psychotic disorders and the genetic risk factors associated with them, to facilitate the development of better diagnostic tools and treatments.
