Measuring Depression: Using biomarkers to investigate the biology of depression

测量抑郁症：使用生物标志物研究抑郁症的生物学

• 批准号: 10313696
• 负责人: Julia Sealock
• 金额: $ 3.08万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2022-05-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10313696
• 关键词: Academic Medical Centers; Affect; Anti-Inflammatory Agents; Antidepressive Agents; Antiinflammatory Effect; Attenuated; Automobile Driving; Biochemical; Biologic Development; Biological; Biological Markers; Biological Process; Biology; Blood Circulation; Brain region; Cells; Clinic; Clinical; Complete Blood Count; Complex; Coronary Arteriosclerosis; Country; Data; Diabetes Mellitus; Diagnosis; Disease; Electronic Health Record; Environmental Risk Factor; Future; Genes; Genetic; Genetic Markers; Genetic Research; Genetic Risk; Genetic Variation; Genetic study; Goals; Immune; Immune system; Immunologic Markers; Individual; Inflammatory; Interview; Investigation; Laboratories; Lead; Link; Measurement; Measures; Mediation; Mediator of activation protein; Medical; Mental Depression; Mental disorders; Methods; Modeling; Patients; Pharmaceutical Preparations; Phenotype; Physicians; Play; Population; Positioning Attribute; Resources; Role; Sample Size; Scanning; Selective Serotonin Reuptake Inhibitor; Smoking; Surveys; Test Result; Testing; Training; Variant; White Blood Cell Count procedure; antidepressant effect; base; biobank; career; circulating biomarkers; clinical care; comorbidity; cost; diagnostic panel; disability; druggable target; epidemiology study; genetic analysis; genetic information; genetic risk factor; genome wide association study; immune activation; immune depression; inflammatory marker; novel; pleiotropism; psychogenetics; response; training opportunity; treatment response

Abstract Depression is a leading cause of disability worldwide, affecting 1 in 6 individuals. Despite the global burden, biology of depression remains poorly understood. Laboratory testing provides physicians with targeted biochemical measurements, biomarkers, to aid in diagnosing and treating patients for a variety of diseases. Biomarker results stored in electronic health records (EHRs) are a largely untapped resource for research. Previous epidemiologic studies identified associations between depression status and various biomarkers, most notably immune markers. However, the direction of association and underlying biology between depression and the immune system has not been described. We hypothesize that integrating genetics of depression with EHR-based biomarker and mediation data will help inform biological processes occurring in depression. In previous analyses, we created a lab-wide association study (LabWAS) framework as a hypothesis-generating approach to scan for associations between polygenic scores (PGS) and biomarkers stored in EHRs. Our method allows for an investigation of biomarkers at an unprecedented scale with both the number of individuals and the number of biomarkers included in the analyses, giving us the opportunity to replicate previous biomarker associations as well as identify novel ones. We discovered an association between depression PGS and an increased immune marker, white blood cell count (WBC) which replicated across multiple biobanks. We plan to further investigate this relationship throughout the proposal. We plan to investigate our hypothesis using two aims: Aim 1 will evaluate whether a phenotype or genetic factors explains the association between depression genetics and WBC. Depression diagnosis is often comorbid with other medical conditions that have known effects on WBC results. We will first conduct sensitivity analyses by covarying for potentially confounding diagnoses in the analysis between depression PGS and WBC. We will then perform conditional analyses to parse the direction of association and underlying genetic regions driving the association. Aim 2 will characterize the role of depression genetics in moderating the relationships between depression diagnosis and antidepressant usage with WBC. Antidepressant treatment with antidepressants has previously been associated with changes in circulating biomarkers. By leveraging medication information in EHRs, we plan to examine the effect of antidepressants on immune biomarker levels, determine the moderating role of depression PGS, and determine if immune biomarker levels associate with treatment response. Successful completion of this project would be the first to analyze the effect of depression genetics on the landscape of biomarkers at scale, parse the direction of association and identify genetic mediators between depression and the immune system, and investigate the effects of genetics on changes in immune system from depression treatment. The future impact of these results could include the development of biologically-informed treatment options, diagnostic panels, and phenotypic subtyping.

摘要