Biopsychosocial Risk Factors for Psychiatric Disorders Following Kidney Transplantation

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Project Summary Psychiatric disorders are highly prevalent following kidney transplantation (KT) and significantly reduce the survival and quality of life of KT recipients. KT is a severely limited resource, and extensive efforts are made by transplant programs to anticipate post-KT co-morbidities. However, major depressive disorder (MDD) and post- traumatic stress disorder (PTSD) both have ~20% point prevalence in KT recipients. The overarching aim of this proposal is to systematically investigate genomic, clinical, and psychosocial contributors to MDD and PTSD following KT. The specific aims are: 1) generate a retrospective electronic health record-based cohort of KT recipients to characterize biopsychosocial risk factors for psychiatric disorders post-KT; 2) establish a prospective cohort of KT candidates to follow trajectories of psychiatric symptoms and risk factors; and 3) develop a predictive model for psychiatric disorders in KT recipients. Kidney disease disproportionately impacts traditional minorities, and most KT recipients are not of European ancestry. When calculating genetic risk score for KT recipients, I will leverage new and diverse training sets and a growing toolkit of genomic methods to appropriately estimate genetic risk across ancestry. I anticipate that this work will improve our ability to understand and mitigate risk of psychiatric disorders for kidney disease patients more broadly and will build on efforts to apply genomic data to patients with non-European ancestry. Dr. Nash is a physician-scientist deeply committed to her primary career goal of improving the mental health of severely ill patients, with an emphasis on those awaiting or living with a solid organ transplant. Her long-term research goal is to build clinical registries with genomic data to elucidate risk factors and etiology of psychiatric disorders in solid organ transplant recipients that will inform the future ideal of personalized, targeted, and pre- emptive treatment for those at risk for psychiatric co-morbidities. Dr. Nash has a PhD in biological chemistry with a strong scientific background, is a fellowship-trained Psychiatrist, and now requires training in clinical research and psychiatric genetics to accomplish her goals as an independently funded investigator. The research outlined in this proposal will provide the necessary training in 1) the design, management, and statistical analysis of clinical databases; 2) survey methodology to capture psychological traits during prospective cohort studies; and 3) GWAS data interpretation and calculation of genetic risk scores. Dr. Nash has built a core mentorship team consisting of Dr. Samantha Meltzer-Brody (co-lead mentor), a physician-scientist and internationally recognized expert in mood disorders; Dr. Patrick Sullivan (co-lead mentor), a world-renowned psychiatric geneticist; Dr. Yun Li (co-mentor), a statistical geneticist who developed core methods for genomics, including imputation and genetic association; and Dr. David Gerber (co-mentor), Chief of Abdominal Transplant at UNC who has published widely in the field including work examining survival benefits and long-term outcomes for transplant patients. Their combined mentorship will allow Dr. Nash to succeed as an independent investigator.