This project employs a multi-method, transdisciplinary approach that combines ethnographic participant- observation, interview research methods, ethical, legal, and public policy analyses. The two goals of the present project are 1) to identify the ethical, legal, and policy challenges that the field of psychiatric genomics will face when trying to translate the findings of large-scale GWAS into clinically useful information, and 2) to make evidence-based recommendations about how to address these challenges. To achieve these goals, I will use, as a case study, one of the first attempts to translate large-scale psychiatric genomics GWAS findings, the Genomics of Treatment-Resistant Psychosis (GTRP) study. GTRP will perform whole exome sequencing (WES) in a sample of 1,000 institutionalized patients who suffer from treatment-resistant psychosis (TRP). GTRP's goals are to identify genomic variants associated with TRP, and ascertain whether any clinically actionable information emerges from these genomic tests that could help improve mental health care for particular patient-participants. I propose to study GTRP's experience to address three research aims critical to understanding the challenges faced in translational psychiatric genomics research with severely mentally ill patients.
Aim 1 will be the mentored research phase of the project, and Aims 2 and 3 will be the independent research phases.
Aim 1 a employs ethnographic participant-observation and interview methods to study the factors that influence GTRP researchers' decision-making process while designing and conducting the WES consent process and the return of results (RoR) components of their study.
Aim 1 b employs ethical analysis to evaluate the design of the GTRP study, including the WES consent process and RoR components.
Aim 1 c employs legal and policy analyses to examine the regulatory framework currently in place to protect institutionalized severely mentally ill patients who participate in translational psychiatric WES research.
Aim 2 a is an empirical examination informed by Aim 1 that employs interview methods to study the views and preferences of GTRP patient-participants, patient-participants' legal guardians or authorized representatives (LG/AR), patient-participants' mental health clinicians, and officials of the mental health institutions in which GTRP will take place. The interviews will assess their perspectives regarding how to handle the WES consent process, selection of results to return, RoR consent process, actual RoR procedure, and the Post-RoR management of WES findings.
Aim 2 b employs legal analysis to examine what kind of legal responsibility, if any, LG/ARs, clinicians, and mental health institutions, assume regarding the management of WES findings once these are returned by researchers (Post-RoR management).
Aim 3 employs ethical and legal analyses to explore the implications of applying a legal Fiduciary Relationship Model (FRM) for defining the ethical responsibilities that different parties hold towards patient- participants in translational psychiaric genomics research. This work will be informed by the data collected in Aims 1 and 2.

Public Health Relevance

This project will identify the ethical, legal, and policy challenges that genomic scientists face when attempting to convert the identification of genes associated with mental health disorders into information and technologies that can improve treatment and prevention. The identification and analysis of these challenges will allow this project to generate evidence-based recommendations about how to protect the interests of the mentally ill patients who participate in these studies. The protection of vulnerable populations that participate in research is a fundamental requirement of any study. Therefore, this project will advance psychiatric genomics medicine by providing guidance to scientists and other relevant parties involved in translational psychiatric genomics research.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Career Transition Award (K99)
Project #
5K99HG008689-02
Application #
9116922
Study Section
Societal and Ethical Issues in Research Study Section (SEIR)
Program Officer
Mcewen, Jean
Project Start
2015-08-01
Project End
2017-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Other Health Professions
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Char, Danton S; Lázaro-Muñoz, Gabriel; Barnes, Aliessa et al. (2017) Genomic Contraindications for Heart Transplantation. Pediatrics 139:
Lázaro-Muñoz, Gabriel; McGuire, Amy L; Goodman, Wayne K (2017) Should we be concerned about preserving agency and personal identity in patients with Adaptive Deep Brain Stimulation systems? AJOB Neurosci 8:73-75
Lázaro-Muñoz, Gabriel; Diaz-Mataix, Lorenzo (2016) Manipulating Human Memory Through Reconsolidation: Stones Left Unturned. AJOB Neurosci 7:244-247
Conley, John M; Lázaro-Muñoz, Gabriel; Prince, Anya E R et al. (2015) Scientific Social Responsibility: Lessons From the Corporate Social Responsibility Movement. Am J Bioeth 15:64-6