Alysa Doyle - Center for Genomic Medicine

Dr. Doyle is a practicing child and adult clinical psychologist trained in psychiatric genetics, developmental psychopathology and pediatric neuropsychology. Her research aims to contribute to and leverage genetic discoveries in order to clarify the complex risk mechanisms that lead to neuropsychiatric illness across the lifespan. She also aims to use these data to identify opportunities for risk stratification and early intervention that can improve patient outcomes in child psychiatry. She is the recipient of several awards including a Dissertation Research Award from the American Psychological Association, a 50^th Anniversary Scholars in Medicine Fellowship from Harvard Medical School and a Clinical Research Day Team Award from Massachusetts General Hospital. Her research is funded by the NIH as well as by the Stanley Center for Psychiatric Research and other private foundations.

Questions being addressed in the lab

How can we leverage discoveries in neuropsychiatric genetics to improve patient outcomes in child psychiatry?
What is the role of cognition in the liability that is shared across different forms of neuropsychiatric illness? Can interventions that target cognition improve patient outcomes?
Can DNA sequence data contribute to the clinical evaluation of youth with severe neuropsychiatric illness?

Projects underway to answer these questions

We have developed a research partnership with a pediatric neuropsychiatric assessment clinic at MGH. To date, we have collected DNA and cognitive and psychiatric phenotypes on over 1400 youth referred for neuropsychiatric evaluation. We are growing this cohort in order to conduct cross-sectional clinical translational analyses of common genetic risk variants. We also aim to follow these youth over time to relate genetic risk profiles to young adult outcomes.
Cognitive impairments are found in a range of neuropsychiatric conditions that are known to share genetic underpinnings. In the LOGIC cohort, we are investigating the possibility that cognition partially mediates the genetic risk that is shared across different types of psychopathology.
We have collaborated with another CGM faculty member, Dr. Talkowski, who has developed a strategy for whole genome sequencing based on large-insert jumping libraries. We used this method to characterize a pilot sample of 30 youth with severe neuropsychiatric presentations (including early onset psychosis or mood disorders or ADHD or ASD with notable comorbidities and/or a history of psychiatric hospitalization).

Answers Found

A specific question we are examining is whether risk for typically adult-onset mental illness relates to traits in our youth clinical cohort that could be amenable to intervention. We have found an association between polygenic risk for SCZ and working memory across diagnoses in our pilot sample.
We have shown that executive cognition associates with dimensions of autism spectrum disorder (ASD), bipolar disorder and psychosis that can be modeled as a general psychopathology factor. We are now extending this model to include common genetic variation. We are also conducting randomized, double-blind placebo-controlled trials of computerized cognitive training in youth with neuropsychiatric illness.
In youth referred for neuropsychiatric evaluation, we found evidence of complex DNA sequence rearrangements, including three of potential clinical significance, that would have been cryptic to chromosomal microarray or karyotyping. Further work is needed to determine whether balanced and cryptic structural variation may warrant evaluation in youth with severe neuropsychiatric illness.