THE ROLE OF LITHIUM IN THE TREATMENT OF BIPOLAR DISORDER: IDENTIFYING CLINICAL AND GENETIC PREDICTORS OF RESPONSE TO LITHIUM TREATMENT
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Date
2020-07-08
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Johns Hopkins University
Abstract
Lithium is one of the most effective treatments for bipolar disorder (BD) and is typically recommended as first-line therapy. However, the efficacy of lithium varies widely from person to person, with about 30% of patients showing partial response and another 25% no response. As a result, it would be beneficial to identify factors which predict who may respond better than others so treatment could be targeted to the appropriate patients. A growing body of evidence suggests that demographic, clinical, and genetic factors may play a role in determining the variability in treatment response. These studies, however, have typically been retrospective or were not specifically designed to examine predictors of response, and the results have been inconsistent.
This thesis examines the role of lithium in the treatment of BD and seeks to identify clinical and genetic predictors that may be used to help guide personalized treatment decisions about which patients would most benefit from treatment. The first contribution of the thesis is a characterization of trends in lithium utilization for the treatment of BD in the U.S. over the past twenty years. To analyze the changing patterns in the management of BD, we use data from the National Ambulatory Medical Care Survey and examined trends in prescriptions of lithium along with other medication categories in visits for BD.
The second contribution of the thesis is an evaluation of clinical predictors associated with response to lithium treatment over time. Using prospective treatment data from the Pharmacogenomics of Bipolar Disorder (PGBD) study, we sought to identify clinical predictors of lithium response in an attempt to determine the clinical characteristics of lithium responders and non-responders prior to initiating treatment.
The third contribution of the thesis is to examine genetic predictors of response to lithium. Using genetic data from the PGBD and reference expression quantitative trait loci (eQTL) data derived from brain samples from the Lieber Institute for Brain Development, we tested for polygenic risk scores as predictors of lithium response, and we used a novel application of the transcriptome-wide association (TWAS) approach to identify specific genes that are associated with lithium response.
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bipolar disorder, lithium, treatment response, clinical predictors, genetic predictors, PRS, TWAS